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Hu HT, Wang P, Jiang YJ, Wang HK, Shao XX, Tian YT. Nomogram-based prognostic stratification for resectable gastric signet-ring cell carcinoma and adenocarcinoma: A retrospective cohort study. World J Gastrointest Oncol 2025; 17:106244. [DOI: 10.4251/wjgo.v17.i5.106244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/02/2025] [Accepted: 03/11/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Gastric signet-ring cell carcinoma (GSRCC) is a more aggressive subtype of gastric cancer compared to gastric adenocarcinoma (GA), with an increasing incidence. However, the prognostic differences between these subtypes, particularly in resectable cases, remain unclear.
AIM To evaluate prognostic factors and develop a predictive model for GA and GSRCC patients undergoing curative resection.
METHODS This retrospective cohort study included patients with GA and GSRCC who underwent curative surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, from 2011 to 2018. Propensity score matching (PSM) (1:1) balanced the baseline characteristics. Prognostic factors were identified using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Model performance was evaluated through calibration curves, decision curve analysis (DCA), and time-dependent receiver operating characteristic curves. Subgroup analysis and Kaplan-Meier survival curves were generated.
RESULTS In a cohort of 3027 patients, the GSRCC group was characterized by a significantly higher prevalence of individuals under 60 years of age, females, cases with poor differentiation, and early-stage (stage I) disease (all P < 0.001). After PSM, the baseline was balanced and 761 patients were retained in each group. Variables identified through univariate Cox regression were included in the LASSO regression analysis. Multivariate Cox regression analysis identified age, tumor differentiation, tumor size, vascular invasion, and post-treatment nodal margin staging as independent prognostic factors. Subgroup analysis indicated a notably poorer prognosis for GSRCC in patients aged 60 and above (hazard ratio = 1.36, P = 0.025). The nomogram (C-index = 0.755) exhibited greater predictive accuracy than tumor node metastasis (TNM) staging for 1-, 3-, and 5-year overall survival (all P < 0.001), and provided a higher clinical net benefit according to DCA.
CONCLUSION This study systematically compared resectable GA and GSRCC, revealing no overall survival difference. However, GSRCC demonstrated a significantly elevated mortality risk in subgroups stratified by age and tumor size. Multivariate analysis identified age, differentiation, tumor size, vascular invasion, and TNM stage as independent prognostic factors. The nomogram integrates clinicopathological features for precise risk stratification, surpassing traditional TNM staging.
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Affiliation(s)
- Hai-Tao Hu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peng Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yu-Juan Jiang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hai-Kuo Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xin-Xin Shao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yan-Tao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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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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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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Saitoh Y, Takeda K, Okawachi K, Tanimura Y. High dose of ascorbic acid induces selective cell growth inhibition and cell death in human gastric signet-ring cell carcinoma-derived NUGC-4 cells. Biochim Biophys Acta Gen Subj 2025; 1869:130738. [PMID: 39675589 DOI: 10.1016/j.bbagen.2024.130738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/04/2024] [Accepted: 12/09/2024] [Indexed: 12/17/2024]
Abstract
Anticancer effects of high-dose vitamin C (VC) have been evaluated on many cancer cell lines, and its efficacy in clinical trials and in combination with anticancer drugs or radiation have been reported; however, its effect on gastric cancer and its mechanisms remain unclear. In the present study, the cell growth inhibitory/lethal effects of high-dose ascorbic acid (AsA), a reduced form of VC was examined on three gastric cancer cell lines. Of these, signet ring cell carcinoma NUGC-4 cells were the most sensitive, but the effects were small and limited in normal cells. Second, high-dose AsA was effective in NUGC-4 cells, whereas dehydroascorbic acid, an oxidized form of VC, was less effective. Third, high-dose AsA showed stronger cell growth inhibitory/lethal effects on floating cells than on adherent cells, and was effective even under hypoxic microenvironment conditions. A single 1-h treatment of high-dose AsA strongly inhibited cell growth, causing apoptosis-like cell death over 72 h after treatment, triggered by hydrogen peroxide generation, actin abnormality, DNA synthesis suppression, DNA damage induction, and ATP level decrease. The effects of high-dose AsA were inhibited either by adding or chelating iron ions, but was not affected via inhibiting AsA transport. Inhibition of glutathione synthesis enhanced the anticancer effects of high-dose AsA. These results indicate that a single high-dose of AsA induces cancer cell-selective, sustained cell growth inhibition and cell death, and these effects may be regulated by iron ion and/or intracellular oxidative stress levels in human gastric signet-ring cell carcinoma-derived NUGC-4 cells.
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Affiliation(s)
- Yasukazu Saitoh
- Program in Biological System Sciences Graduate School of Comprehensive Scientific Research, Prefectural University of Hiroshima, 5562, Nanatsuka, Shobara, Hiroshima 727-0023, Japan; Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562, Nanatsuka, Shobara, Hiroshima 727-0023, Japan.
| | - Kaori Takeda
- Program in Biological System Sciences Graduate School of Comprehensive Scientific Research, Prefectural University of Hiroshima, 5562, Nanatsuka, Shobara, Hiroshima 727-0023, Japan
| | - Koichi Okawachi
- Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562, Nanatsuka, Shobara, Hiroshima 727-0023, Japan
| | - Yusuke Tanimura
- Program in Biological System Sciences Graduate School of Comprehensive Scientific Research, Prefectural University of Hiroshima, 5562, Nanatsuka, Shobara, Hiroshima 727-0023, Japan
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Liveraro GS, Takahashi ME, Lascala F, Lopes LR, Andreollo NA, Mendes MC, Takahashi J, Carvalheira JB. Improving resectable gastric cancer prognosis prediction: A machine learning analysis combining clinical features and body composition radiomics. INFORMATICS IN MEDICINE UNLOCKED 2025; 52:101608. [DOI: 10.1016/j.imu.2024.101608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
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Maruyama S, Imamura Y, Toihata T, Haraguchi I, Takamatsu M, Yamashita M, Nakashima Y, Oki E, Taguchi K, Yamamoto M, Mine S, Okamura A, Kanamori J, Nunobe S, Sano T, Kitano S, Noda T, Watanabe M. FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor. Cancer Sci 2025; 116:178-191. [PMID: 39440906 PMCID: PMC11711055 DOI: 10.1111/cas.16373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 09/21/2024] [Accepted: 10/03/2024] [Indexed: 10/25/2024] Open
Abstract
The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.
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Affiliation(s)
- Suguru Maruyama
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tasuku Toihata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ikumi Haraguchi
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Manabu Takamatsu
- Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makiko Yamashita
- Advanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuichiro Nakashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichi Taguchi
- Department of Pathology, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan
| | - Manabu Yamamoto
- Department of Gastroenterological Surgery, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan
| | - Shinji Mine
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, Tokyo, Japan
| | - Akihiko Okamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Jun Kanamori
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shigehisa Kitano
- Advanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tetsuo Noda
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
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Costa M, Lopes Fernandes C, Magalhães H. Perioperative Treatment in Gastric Cancer: A Fast-Changing Field. Cancers (Basel) 2024; 16:4036. [PMID: 39682222 DOI: 10.3390/cancers16234036] [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: 10/28/2024] [Revised: 11/21/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Gastric cancer is the fifth most common cancer worldwide and its incidence is rising. Surgery is the only curative strategy and its association with perioperative chemotherapy is now standard treatment for most resectable tumors. Despite treatment advances, disease relapse is high, even in early stages, and continued improvement in curative treatment is imperative. With deeper knowledge of gastric cancer heterogeneity, molecular subtypes, and the tumor immune microenvironment, new standard treatment strategies may emerge in the near future. This paper provides a comprehensive review of the current treatment landscape in resectable gastric cancer and future perspectives for the next decade regarding new agents such as targeted therapies, immunotherapy, antibody-drug conjugates, and the combination of multiple treatment modalities.
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Affiliation(s)
- Mafalda Costa
- Medical Oncology Department, Pedro Hispano Hospital, 4464-513 Matosinhos, Portugal
| | | | - Helena Magalhães
- Medical Oncology Department, Pedro Hispano Hospital, 4464-513 Matosinhos, Portugal
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Hui X, Zhou G, Zheng Y, Wang Y, Guo Q. Development and validation of a tumor size-stratified prognostic nomogram for patients with gastric signet ring cell carcinoma. Updates Surg 2024; 76:2813-2824. [PMID: 39495439 PMCID: PMC11628570 DOI: 10.1007/s13304-024-02020-0] [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: 04/25/2024] [Accepted: 09/28/2024] [Indexed: 11/05/2024]
Abstract
Gastric signet ring cell carcinoma (GSRC) is a rare malignancy without a commonly acknowledged prognostic assessment and treatment system. This study aimed to determine the optimal cut-off value of tumor size (TS), and construct a prognostic nomogram in combination with other independent prognostic factors (PFs) to predict 3 year and 5 year overall survival (OS) in GSRC patients. From the Surveillance, Epidemiology, and End Results (SEER) database, this study collected 4744 patients diagnosed with GSRC. These patients were randomized into a training cohort (n = 2320,) and a validation cohort (n = 1142). A restricted cubic spline (RCS) was used to determine the cut-off value for TS, and univariate and multivariate Cox regression analyses were performed in the training cohort to identified significant predictors. A prognostic nomogram was constructed to predict OS at 3 and 5 years. Concordance index (C index), receiver operating characteristics curve (ROC curve), area under curve (AUC), and calibration curve were used to test the predictive accuracy of the model. A non-linear relationship was observed between TS and the risk of OS in GSRC, with TS thresholds at 4.4 cm and 9.6 cm. Survival was significantly lower in GSRC patients with TS > 4.4 cm. Age, marriage, chemotherapy, surgery, TS, SEER stage, regional lymph node status, and total number were independent predictors of OS. The C index in the training cohort was 0.748, and the AUC values for both 3- and 5-year OS were higher than 0.80. Similar results were observed in the validation cohort. In addition, the calibration curves showed good agreement between the predicted 3 year and 5 year OS and the actual OS. TS is a key prognostic factor for patients with GSRC, and patients with a TS of 4.4-9.6 cm and > 9.6 cm may have a poorer prognosis than those with a TS of < 4.4 cm. The TS-stratified nomogram we constructed and validated has favorable accuracy and calibration precision, and may be helpful in predicting the survival rate of patients.
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Affiliation(s)
- Xin Hui
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
| | - Guangbo Zhou
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
| | - Ya Zheng
- Department of Gastroenterology, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China
| | - Qinghong Guo
- Department of Gastroenterology, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China.
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu Province, China.
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Del Carmen Fernández-Moreno M, Barrios-Carvajal ME, Martí-Obiol R, Gadea-Mateo R, Martín-Arévalo J, López-Mozos F. Prognostic insights after surgery for advances in understanding signet ring cell gastric cancer: a machine learning approach. J Gastrointest Surg 2024; 28:2055-2066. [PMID: 39368648 DOI: 10.1016/j.gassur.2024.09.030] [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: 07/10/2024] [Revised: 09/20/2024] [Accepted: 09/28/2024] [Indexed: 10/07/2024]
Abstract
BACKGROUND Signet ring cell (SRC) gastric carcinoma is traditionally associated with a poor prognosis. However, the literature has presented contradictory results. Linear models are the standard statistical tools typically used to study these conditions. However, machine learning (ML) models have the potential to replace or even outperform linear models in terms of predictive performance. METHODS This study analyzed 608 patients diagnosed with gastric cancer at our institution. The analysis compared traditional linear models and ML models. Variables examined included demographic data, presence of an SRC component, lymph nodes (LNs) resected and affected (ratio), stage of the disease, body mass index, pathologic features, type of surgery, tumor location, and carcinoembryonic antigen levels to evaluate their influence on 5-year mortality and 2-year recurrence rates. RESULTS SRC carcinoma was associated with poorer prognosis in terms of 5-year overall survival than non-SRC carcinoma. In addition, SRC exhibited higher rates of LN metastasis and a higher LN ratio (resected/affected) and was more prevalent in younger patients (<65 years). However, SRC was not an independent factor in the multivariate analysis. Linear models showed worse predictions for 5-year mortality and 2-year recurrence than ML models. The ML models did not consider the presence of the SRC component as an important variable. CONCLUSION SRC gastric carcinoma continues to present an uncertain prognosis. ML models can evaluate prognosis more accurately than traditional linear models. Large-scale studies using ML algorithms are necessary to elucidate the predictive potential of such models.
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Affiliation(s)
- María Del Carmen Fernández-Moreno
- Upper Gastrointestinal and Peritoneal Oncology Surgery Unit, Department of General Surgery, Universitat de Valencia, Valencia, Spain
| | - María Eugenia Barrios-Carvajal
- Upper Gastrointestinal and Peritoneal Oncology Surgery Unit, Department of General Surgery, Universitat de Valencia, Valencia, Spain
| | - Roberto Martí-Obiol
- Upper Gastrointestinal and Peritoneal Oncology Surgery Unit, Department of General Surgery, Universitat de Valencia, Valencia, Spain
| | - Ricardo Gadea-Mateo
- Upper Gastrointestinal and Peritoneal Oncology Surgery Unit, Department of General Surgery, Universitat de Valencia, Valencia, Spain
| | - Jose Martín-Arévalo
- Colorectal Surgery Unit, Department of General Surgery, Universitat de Valencia, Valencia, Spain; Investigation Quality Committee, Clinic University Hospital, Universitat de Valencia, Valencia, Spain
| | - Fernando López-Mozos
- Upper Gastrointestinal and Peritoneal Oncology Surgery Unit, Department of General Surgery, Universitat de Valencia, Valencia, Spain; Investigation Quality Committee, Clinic University Hospital, Universitat de Valencia, Valencia, Spain.
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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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11
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Yu C, Yang J, Li H, Wang J, Jin K, Li Y, Zhang Z, Zhou J, Tang Y. Prognostic prediction and treatment options for gastric signet ring cell carcinoma: a SEER database analysis. Front Oncol 2024; 14:1473798. [PMID: 39497709 PMCID: PMC11532132 DOI: 10.3389/fonc.2024.1473798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/02/2024] [Indexed: 11/07/2024] Open
Abstract
Background In recent years, the overall incidence of gastric cancer has decreased. However, the incidence of gastric signet ring cell carcinoma (SRCC) is still increasing year by year. Compared with other subtypes (non-SRCC) such as adenocarcinoma, SRCC usually exhibits a more aggressive biological behavior. Therefore, studying the prognostic differences and factors associated with SRCC is essential to improve the accuracy of diagnosis and prognosis. The purpose of this study was to investigate the prognostic factors influencing the prognosis of patients with SRCC and to develop personalized treatments for different subgroups of patients. Methods The data on gastric SRCC patients and gastric adenocarcinoma (AC) patients from 1992 to 2020 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The data of gastric SRCC as the external validation group was reviewed from the First Affiliated Hospital of Soochow University. The overall survival (OS) and cancer specific survival (CSS) at 1 and 2 years were predicted for SRCC patients by constructing prognostic nomograms. A series of validation methods, including Akaike information criterion (AIC), decision curve analysis (DCA), calibration curve analysis, the concordance index (C-index) and the area under the receiver operating characteristic (AUC) curve, were used to verify the accuracy and reliability of the models. Results In all, 549 patients with SRCC were included after propensity score matching (PSM). Multivariate Cox regression analysis showed that T stage, N stage, M stage and surgical approach were independent risk factors affecting the prognosis of SRCC patients. A prognostic nomogram was constructed and validated as an accurate model for SRCC patients after scoring by receiver operating characteristic curve (ROC) curves and calibration plots. The patients were further divided into high-risk and low-risk groups, and the Kaplan-Meier curves showed that SRCC patients in the low-risk group could receive only surgery without chemotherapy, while chemotherapy plus surgery was a better option for SRCC patients in the high-risk group. Conclusion The prognosis for SRCC was less favorable than that of AC in terms of CSS. The nomograms were developed and validated to predict OS and CSS in patients with SRCC, helping in developing appropriate individualized treatment schedules.
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Affiliation(s)
- Chengqing Yu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Yang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Haoran Li
- Department of Gastrointestinal Surgery, Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou, China
| | - Jie Wang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Kanghui Jin
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yifan Li
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zixiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Zhou
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Yuchen Tang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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12
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Xu J, Yu B, Wang F, Yang J. Single-cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy. Cancer Immunol Immunother 2024; 73:233. [PMID: 39271545 PMCID: PMC11399521 DOI: 10.1007/s00262-024-03820-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024]
Abstract
Gastric cancer (GC) is a highly heterogeneous disease with a complex tumor microenvironment (TME) that encompasses multiple cell types including cancer cells, immune cells, stromal cells, and so on. Cancer-associated cells could remodel the TME and influence the progression of GC and therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into the complicated biological composition and characteristics of TME at the molecular, cellular, and immunological resolutions, offering a new idea for GC studies. In this review, we discuss the novel findings from scRNA-seq datasets revealing the origin and evolution of GC, and scRNA-seq is a powerful tool for investigating transcriptional dynamics and intratumor heterogeneity (ITH) in GC. Meanwhile, we demonstrate that the vital immune cells within TME, including T cells, B cells, macrophages, and stromal cells, play an important role in the disease progression. Additionally, we also overview that how scRNA-seq facilitates our understanding about the effects on individualized therapy of GC patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution and capture local intercellular communication networks, enabling a further understanding of the relationship between the spatial background of a particular cell and its functions. In summary, scRNA-seq and other single-cell technologies provide a valuable perspective for molecular and pathological disease characteristics and hold promise for advancing basic research and clinical practice in GC.
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Affiliation(s)
- Jiao Xu
- Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Bixin Yu
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Fan Wang
- Phase I Clinical Trial Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
| | - Jin Yang
- Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China.
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China.
- Phase I Clinical Trial Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
- Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
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13
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Guío-Ávila JI, Soler-Perilla AY, Briceño-Morales X, Briceño-Morales C. Gastric signet ring cell adenocarcinoma metastatic to the breast. Systematic review of the literature, regarding a case. REVISTA COLOMBIANA DE OBSTETRICIA Y GINECOLOGIA 2024; 75:4187. [PMID: 39470266 PMCID: PMC11584199 DOI: 10.18597/rcog.4187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 09/02/2024] [Indexed: 10/30/2024]
Abstract
Objectives To determine the general state of scientific evidence published in the last 20 years on gastric signet ring cell (SRC) adenocarcinoma metastatic to the breast, and present a case. Material and methods The case of a patient who attended a high-complexity reference institution in Bogotá for a breast metastasis from a gastric SRC adenocarcinoma is reported. A Systematic Review of the literature was carried out, including cohort studies, reports and case series of patients with gastric SRC adenocarcinoma metastatic to the breast, which will present information on the epidemiology, clinical, radiological and histopathological characteristics, and the treatment and prognostic of this disease. Results There were identified 363 references, twenty-six of which met the eligibility criteria. Gastric SRC adenocarcinoma metastatic to the breast predominated in the Asian continent (75.9%). The mean age at presentation was 42.5 years. In 62% (n=18) of cases this condition manifested clinically as a breast mass. From a radiological point of view, the majority of breast lesions presented as one or several nodules with suspicious characteristics (55.2%; n=16). In the biopsy of breast lesions, positivity for cytokeratin 7 and cytokeratin 20 occurred in 41.4% (n=12) and 37.9% (n=11) of cases, respectively. Only nine patients (31%) underwent any type of breast surgery. There is a lack of information on the treatment and prognosis of gastric SRC adenocarcinoma metastatic to the breast. Conclusions The frequency of cases of gastric SRC adenocarcinoma metastatic to the breast published in the last 20 years is low. The general practitioner and the gynecologist could be the first medical professionals to face this rare condition, so knowing it and suspecting it is essential, especially if we take into account that the median overall survival of these patients is low.
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Affiliation(s)
- José Ismael Guío-Ávila
- Profesor Titular, Departamento de Ginecología y Obstetricia, Hospital de San José de Bogotá, Fundación Universitaria de Ciencias de la Salud. Bogotá (Colombia)
| | - Adriana Yulieth Soler-Perilla
- Residente de cuarto año de Ginecología y Obstetricia, Hospital de San José de Bogotá, Fundación Universitaria de Ciencias de la Salud. Bogotá (Colombia)
| | - Ximena Briceño-Morales
- Especialista en Mastología, Instituto Nacional de Cancerología. Bogotá (Colombia); Departamento de Obstetricia y Ginecología, Facultad de Medicina, Universidad Nacional de Colombia. Bogotá (Colombia)
| | - Clara Briceño-Morales
- Especialista en Cirugía Oncológica. Grupo de Investigación en Ciencias Quirúrgicas, Universidad Tecnológica de Pereira. Pereira (Colombia); Institución Universitaria Visión de las Américas. Pereira (Colombia)
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14
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Perrot-Applanat M, Pimpie C, Vacher S, Pocard M, Baud V. High Expression of AhR and Environmental Pollution as AhR-Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients with Gastric Cancer-A Pilot Study. Biomedicines 2024; 12:1905. [PMID: 39200369 PMCID: PMC11351739 DOI: 10.3390/biomedicines12081905] [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: 06/16/2024] [Revised: 07/29/2024] [Accepted: 08/02/2024] [Indexed: 09/02/2024] Open
Abstract
The vast majority of gastric cancer (GC) cases are adenocarcinomas including intestinal and diffuse GC. The incidence of diffuse GC, often associated with poor overall survival, has constantly increased in Western countries. Epidemiological studies have reported increased mortality from GC after occupational exposure to pro-carcinogens that are metabolically activated by cytochrome P450 enzymes through aryl hydrocarbon receptor (AhR). However, little is known about the role of AhR and environmental AhR ligands in diffuse GC as compared to intestinal GC in Western patients. In a cohort of 29, we demonstrated a significant increase in AhR protein and mRNA expression levels in GCs independently of their subtypes and clinical parameters. AhR and RHOA mRNA expression were correlated in diffuse GC. Further, our study aimed to characterize in GC how AhR and the AhR-related genes cytochrome P450 1A1 (CYP1A1) and P450 1B1 (CYP1B1) affect the mRNA expression of a panel of genes involved in cancer development and progression. In diffuse GC, CYP1A1 expression correlated with genes involved in IGF signaling, epithelial-mesenchymal transition (Vimentin), and migration (MMP2). Using the poorly differentiated KATO III epithelial cell line, two well-known AhR pollutant ligands, namely 2-3-7-8 tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (BaP), strongly increased the expression of CYP1A1 and Interleukin1β (IL1B), and to a lesser extend UGT1, NQO1, and AhR Repressor (AhRR). Moreover, the increased expression of CYP1B1 was seen in diffuse GC, and IHC staining indicated that CYP1B1 is mainly expressed in stromal cells. TCDD treatment increased CYP1B1 expression in KATO III cells, although at lower levels as compared to CYP1A1. In intestinal GC, CYP1B1 expression is inversely correlated with several cancer-related genes such as IDO1, a gene involved in the early steps of tryptophan metabolism that contributes to the endogenous AhR ligand kynurenine expression. Altogether, our data provide evidence for a major role of AhR in GC, as an environmental xenobiotic receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support the continued efforts to clarify the identity of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.
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Affiliation(s)
- Martine Perrot-Applanat
- INSERM U1275, Peritoneal Carcimomatosis Paris-Technologies, Hôpital Lariboisiere, Université Paris Cité, 75010 Paris, France; (C.P.); (M.P.)
| | - Cynthia Pimpie
- INSERM U1275, Peritoneal Carcimomatosis Paris-Technologies, Hôpital Lariboisiere, Université Paris Cité, 75010 Paris, France; (C.P.); (M.P.)
| | - Sophie Vacher
- Department of Genetics, Curie Institute, PSL Research University, 75005 Paris, France;
| | - Marc Pocard
- INSERM U1275, Peritoneal Carcimomatosis Paris-Technologies, Hôpital Lariboisiere, Université Paris Cité, 75010 Paris, France; (C.P.); (M.P.)
- Department of Digestive and Oncology Surgery, Hôpital Lariboisiere, Université Paris Cité, 75010 Paris, France
| | - Véronique Baud
- NF-kappaB, Differentiation and Cancer, Faculty of Pharmacy, Université Paris Cité, 75006 Paris, France
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15
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Chu Y, Long F, Ding X, Tian S. The effect of surgery and metastatic risk prediction in patients with gastrointestinal tract signet-ring cell carcinoma. J Gastrointest Surg 2024; 28:1234-1241. [PMID: 38740257 DOI: 10.1016/j.gassur.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/12/2024] [Accepted: 05/08/2024] [Indexed: 05/16/2024]
Abstract
PURPOSE This study aimed to assess the efficacy of surgery as a treatment option for patients with signet-ring cell carcinoma (SRCC) in the gastrointestinal tract (GI-SRCC). METHODS Using the Surveillance, Epidemiology, and End Results database, patients with GI-SRCC who underwent surgery or received nonsurgical treatment were included. Propensity score matching (PSM) analysis was used to balance baseline characteristics and reduce bias. Overall survival (OS) was calculated in matching cohorts to estimate prognosis for patients with GI-SRCC. Nomogram was established to predict metastasis for patients with GI-SRCC. RESULTS The study enrolled a total of 9428 patients with GI-SRCC, with 1689 patients in the nonsurgery group and 7739 patients in the surgery group. After 1:1 PSM, we analyzed 743 patients from each group. Our survival analyses revealed that surgery independently correlated with improved OS for patients with GI-SRCC (hazard ratio, 0.37; 95% CI, 0.33-0.42; P < .001). Subgroup analysis further confirmed the positive impact of surgery on the prognosis of patients with nonmetastatic GI-SRCC. Notably, distinct subsets of patients with metastasis, particularly those originating from the upper GI (esophagus, proximal stomach, and distal stomach) and left colon, demonstrated a significant improvement in OS after surgery. However, no significant survival difference was observed for patients with metastatic right colon and rectum SRCC. Using nomogram, we quantitatively assessed the risk of metastasis in patients with right colon and rectum SRCC, which exhibited robust predictive accuracy, with area under the curve values of 0.829. CONCLUSION Our study highlighted surgery's positive impact on prognosis for both patients with nonmetastatic and metastatic upper GI-SRCC and left colon SRCC. Hence, we recommend surgery as a treatment option for these groups. In addition, for patients with metastatic right colon and rectum SRCC ineligible for surgery, our predictive nomogram can offer a convenient tool to aid early intervention and improve prognosis.
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Affiliation(s)
- Yanan Chu
- Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fei Long
- Laboratory of Pediatric Hematology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xueliang Ding
- Department of Clinical Laboratory, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China
| | - Shaobo Tian
- Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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16
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Chow TK. Isolated Diffuse Bone Marrow Metastases From Signet-ring Cell Gastric Carcinoma. Mol Imaging Radionucl Ther 2024; 33:132-133. [PMID: 38949558 PMCID: PMC11589268 DOI: 10.4274/mirt.galenos.2023.17037] [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: 10/17/2023] [Accepted: 12/29/2023] [Indexed: 07/02/2024] Open
Abstract
A 71-year-old female patient with a known history of signet-ring cell carcinoma presented with diffuse bone pain and anemic symptoms. An 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography study revealed diffuse heterogeneous hypermetabolic sclerotic lesions in the axial and proximal appendicular skeleton. No other 18F-FDG-avid lesions were detected. Subsequent bone marrow biopsy confirmed the diagnosis of metastatic carcinoma originating from the gastric primary site. Palliative treatment was initiated; however, the patient's condition deteriorated, and she succumbed to the disease two months later.
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Affiliation(s)
- Tsz-Kit Chow
- Tuen Mun Hospital Clinic of Radiology and Nuclear Medicine, Nuclear Medicine Unit, Hong Kong, China
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17
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Grinlinton M, Furkert C, Maurice A, Angelo N, Booth M. Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review. World J Gastrointest Surg 2024; 16:1629-1636. [PMID: 38983359 PMCID: PMC11230026 DOI: 10.4240/wjgs.v16.i6.1629] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/23/2024] [Accepted: 04/28/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Upper gastrointestinal (GI) signet ring cell carcinomas (SRCC) confer a poor prognosis. The benefit of operative intervention for this patient group is controversial in terms of overall survival. AIM To investigate factors relating to survival in patients with upper GI SRCC. METHODS A retrospective, tertiary, single-centre review of patients who were diagnosed with oesophageal, gastroesophageal junction and gastric SRCC was performed. The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management. Secondary outcomes included assessing the relationship between demographic and histopathological factors, and survival. RESULTS One hundred and thirty-one patients were included. The one-year survival for the operative group was 81% and for the nonoperative group was 19.1%. The five-year survival in the operative group was 28.6% vs 1.5% in the nonoperative group. The difference in overall survival between groups was statistically significant (HR 0.19, 95%CI (0.13-0.30), P < 0.001). There was no difference in survival when adjusting for age, smoking status or gender. On multivariate analysis, patients who underwent surgical management, those with a lower stage of disease, and those with a lower Charlson Comorbidity Index (CCI) had significantly improved survival. CONCLUSION Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery. Offering surgery to a carefully selected patient group may improve the outcome for this disease.
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Affiliation(s)
- Megan Grinlinton
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
| | - Chris Furkert
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
| | - Andrew Maurice
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
| | - Neville Angelo
- Department of Pathology, North Shore Hospital, Auckland 0620, New Zealand
| | - Michael Booth
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
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Abboretti F, Mantziari S, Didisheim L, Schäfer M, Teixeira Farinha H. Prognostic value of tumor regression grade (TRG) after oncological gastrectomy for gastric cancer. Langenbecks Arch Surg 2024; 409:199. [PMID: 38935163 PMCID: PMC11211110 DOI: 10.1007/s00423-024-03388-8] [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: 03/30/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024]
Abstract
PURPOSE Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression score (TRG) is widely used to evaluate pathological response to neoadjuvant treatment. The aim of this study was to assess the prognostic value of TRG in terms of overall survival (OS) and disease-free (DFS). METHODS Retrospective analysis of all consecutive patients who underwent oncological gastrectomy after neoadjuvant chemotherapy from January 2007 to December 2019 for gastric adenocarcinoma was performed. Based on their TRG status they were categorized into two groups: good responders (TRG 1-2) and poor responders (TRG 3-5). Subsequent multivariable analyses were conducted. RESULTS Seventy-four patients were included, whereby 15 (20.3%) were TRG 1-2. Neoadjuvant regimens for TRG 1-2 vs. TRG 3-5 were similar: MAGIC (53% vs. 39%), FLOT (40% vs. 36%), FOLFOX (7% vs. 15%, p = 0.462). Histologic types according to Lauren classification for TRG 1-2 vs. TRG 3-5 were: 13% vs. 29% intestinal, 53% vs. 44% diffuse and 34% vs. 27% indeterminate (p = 0.326). TRG 1-2 group exhibited significantly less advanced ypT (46% vs. 10%, p = 0.001) and ypN stages (66% vs. 37%, p = 0.008), alongside a diminished recurrence rate (20% vs. 42%, p = 0.111). The 3-year DFS was significantly better in this group (81% vs. 47%, p = 0.041) whereas the disparity in three-year OS (92% vs. 55%, p = 0.054) did not attain statistical significance. CONCLUSIONS TRG 1-2 was associated with less advanced ypT and ypN stage and better DFS compared to TRG 3-5 patients, without a significant impact on OS.
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Affiliation(s)
- Francesco Abboretti
- Department of Visceral Surgery, Lausanne University Hospital, CHUV Rue du Bugnon 46, Lausanne, 1011, Switzerland
- Faculty of Biology and Medicine, University of Lausanne (UNIL), Lausanne, 1015, Switzerland
| | - Styliani Mantziari
- Department of Visceral Surgery, Lausanne University Hospital, CHUV Rue du Bugnon 46, Lausanne, 1011, Switzerland
- Faculty of Biology and Medicine, University of Lausanne (UNIL), Lausanne, 1015, Switzerland
| | - Laura Didisheim
- Department of Visceral Surgery, Lausanne University Hospital, CHUV Rue du Bugnon 46, Lausanne, 1011, Switzerland
| | - Markus Schäfer
- Department of Visceral Surgery, Lausanne University Hospital, CHUV Rue du Bugnon 46, Lausanne, 1011, Switzerland.
- Faculty of Biology and Medicine, University of Lausanne (UNIL), Lausanne, 1015, Switzerland.
| | - Hugo Teixeira Farinha
- Department of Visceral Surgery, Lausanne University Hospital, CHUV Rue du Bugnon 46, Lausanne, 1011, Switzerland
- Faculty of Biology and Medicine, University of Lausanne (UNIL), Lausanne, 1015, Switzerland
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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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Lin J, Chen ZF, Guo GD, Chen X. Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma. World J Gastrointest Oncol 2024; 16:687-698. [PMID: 38577442 PMCID: PMC10989384 DOI: 10.4251/wjgo.v16.i3.687] [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: 11/27/2023] [Revised: 12/27/2023] [Accepted: 02/06/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special staining methods used to detect acidic mucus and neutral mucus, respectively. However, the clinical importance of the special combined AB and PAS stain is unclear. AIM To investigate AB expression, PAS expression and the AB-to-PAS (A/P) ratio in gastric SRCC patients and to assess patient prognosis. METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS, and signet ring cell positivity was assessed quantitatively. Immunohistochemical staining for Ki67, protein 53 (P53) and human epidermal growth factor receptor 2 (HER2) was performed simultaneously. The cancer-specific survival (CSS) rate was estimated via Kaplan-Meier analysis. Cox proportional hazards models were used for univariate and multivariate survival analyses. RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup (P < 0.001). The 3-year CSS rate in the A/P ≤ 0.5 group was significantly greater than that in the A/P > 0.5 group (P = 0.042). Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter, lymph node metastasis, vessel carcinoma embolus, tumor stage, the A/P ratio and the expression of Ki67, P53 and the PAS. Cox multivariate regression analysis confirmed that low PAS expression [hazard ratio (HR) = 3.809, 95% confidence interval (CI): 1.563-9.283, P = 0.003] and large tumor diameter (HR = 2.761, 95%CI: 1.086-7.020, P = 0.033) were independent risk factors for poor prognosis. CONCLUSION A/P > 0.5 is potentially a risk factor for prognosis, and low PAS expression is an independent risk factor in the prognosis of gastric SRCC. PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.
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Affiliation(s)
- Juan Lin
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian Province, China
- Department of Pathology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
| | - Zhu-Feng Chen
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian Province, China
- Department of Internal Medicine, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
| | - Guo-Dong Guo
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian Province, China
- Department of Pathology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
| | - Xin Chen
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian Province, China
- Department of Pathology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
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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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22
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Hong W, Hu Q, Tan Y, Duan Q, Zhang Q, Chen D, Qi C, Wang D. Gastrointestinal signet ring cell malignancy: current advancement and future prospects. Invest New Drugs 2023; 41:861-869. [PMID: 37864727 DOI: 10.1007/s10637-023-01403-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 10/18/2023] [Indexed: 10/23/2023]
Abstract
Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation.
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Affiliation(s)
- Weiping Hong
- Department of Oncology, Guangdong Sanjiu Brain Hospital, 578 Shatai Road, Baiyun District, Guangzhou City, Guangdong Province, China
| | - Qingjun Hu
- Department of Oncology, Guangdong Sanjiu Brain Hospital, 578 Shatai Road, Baiyun District, Guangzhou City, Guangdong Province, China
| | - Yuan Tan
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Qianqian Duan
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Qin Zhang
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Dongsheng Chen
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Chuang Qi
- The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China
| | - Da Wang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Rd., Hangzhou, China.
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Wang W, Xia Y, He C. Development and validation of a predictive model associated with lymph node metastasis of gastric signet ring carcinoma patients. Medicine (Baltimore) 2023; 102:e36002. [PMID: 37960779 PMCID: PMC10637419 DOI: 10.1097/md.0000000000036002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 10/17/2023] [Indexed: 11/15/2023] Open
Abstract
The risk factors for lymph node metastasis (LNM) in patients with gastric signet ring cell carcinoma (GSRC) have not been well-defined. This study was designed to prognosticate LNM in patients with GSRC by constructing and verifying a nomogram. A total of 2789 patients with GSRC from the Surveillance, Epidemiology, and End Results (SEER) database and Yijishan Hospital of Wannan Medical College (YJS) were retrospectively reviewed. A predictive model was established using logistic regression based on the SEER cohort. The performance of the model was evaluated using the concordance index (C-index) and decision curve analysis (DCA). In addition, its robustness was validated using the YJS cohort. Four independent predictors of LNM were identified in the SEER cohort. Next, a nomogram was constructed by incorporating these predictors. The C-index were 0.800 (95% confidence interval [CI] = 0.781-0.819) and 0.837 (95% CI = 0.784-0.890) in the training and external validation cohorts, respectively. The outcomes of DCA supported good clinical benefits. The proposed model for evaluating the LNM in patients with GSRC can help to avoid the misdiagnosis risk of N-stage, assist to screen the population suitable for neoadjuvant therapy and help clinicians to optimize clinical decisions.
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Affiliation(s)
- Wei Wang
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China
| | - Yang Xia
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China
| | - Chiyi He
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China
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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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Ma Y, Wang Y, Hu C, Zi M, Chen J, Cao M, Yuan L, Yang L, Du Y. The percentages of signet-ring cells (SRCs) affects the prognosis after radical gastrectomy for advanced gastric cancer. Langenbecks Arch Surg 2023; 408:376. [PMID: 37743407 DOI: 10.1007/s00423-023-03114-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 09/19/2023] [Indexed: 09/26/2023]
Abstract
PURPOSE Only recently has the percentage of signet-ring cells (SRCs) been shown to affect the prognosis following gastric cancer surgery. It is uncertain whether the SRC percentage has a role in tumour biology or prognosis of gastric signet-ring cell carcinoma (GSRCC). For this research, we assessed the effect of the SRC percentage on the clinicopathological and prognostic characteristics of gastric cancer (GC) tumours and created and verified a prognostic nomogram to assess the overall survival (OS) of GSRCC patients. METHODS In our study, 1100 GC patients with signet-ring cell carcinoma (SRCC) at Zhejiang Cancer Hospital from December 2013 to December 2018 who underwent curative gastric cancer resection were retrospectively analysed. The patients were separated into two groups: those with SRCC (SRC percentage >50%; n = 157) and those with partial signet-ring cell carcinoma (PSRCC) (SRC percentage ≤50%; n = 943). We compared the clinicopathological characteristics of both groups. To estimate OS and determine correlations with the SRC percentage, the Kaplan-Meier method and log-rank test were used. To develop the prognostic nomogram, independent prognostic indicators for OS were identified using Cox regression analyses. Predictions were assessed using the calibration curve and C-index. RESULTS Our research showed that there was no discernible difference in OS between the two groups. The preoperative CA242 level, pT stage, pN stage, age, nerve invasion, neoadjuvant chemotherapy, postoperative chemotherapy, and maximum tumour diameter were independent prognostic risk factors for OS for GC (all p < 0.05). However, for advanced GC, the SRC percentage (HR = 1.571, 95% CI 1.072-2.302, p = 0.020) was an independent prognostic factor of OS. Other independent prognostic risk factors were age, pT stage, pN stage, nerve invasion, tumour location, neoadjuvant chemotherapy, postoperative chemotherapy, preoperative CA50 level, and preoperative CEA level (all p < 0.05). On these bases, nomograms were constructed for GC and advanced GC, with C-indexes of 0.806 (95%CI 0.782-0.830) and 0.728 (95%CI 0.697-0.759), respectively. CONCLUSIONS In cases of advanced gastric cancer, the SRC percentage served as a standalone prognostic indicator for OS. An effective tool for assessing the prognosis of GSRCC was offered by the nomogram.
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Affiliation(s)
- Yubo Ma
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Zhejiang, 310053, Hangzhou, China
| | - Yi Wang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Can Hu
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Zhejiang, 310053, Hangzhou, China
| | - Mengli Zi
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Jinxia Chen
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Mengxuan Cao
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China
| | - Li Yuan
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China.
| | - Litao Yang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China.
| | - Yian Du
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, 310022, Hangzhou, China.
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Shen Y, Li Y, Wang Z, Xu W, Wang W, Chen X. The prognostic value of FAR and a novel FAR-CA125 score in resectable gastric signet ring cell carcinoma patients. J Cancer Res Clin Oncol 2023; 149:9597-9608. [PMID: 37222811 DOI: 10.1007/s00432-023-04870-4] [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: 04/12/2023] [Accepted: 05/19/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND The fibrinogen to albumin ratio (FAR) is increasingly regarded as a potential biomarker for predicting prognosis in variety of malignant tumors, but not in gastric signet ring cell carcinoma (GSRC). This study seeks to examine the prognostic value of the FAR and explore a novel FAR-CA125 score (FCS) in resectable GSRC patients. METHODS A retrospective cohort was conducted including 330 GSRC patients who underwent curative resection. Kaplan-Meier (K-M) and Cox regression were used to analysis the prognostic value of FAR and FCS. And a predictive nomogram model was developed. RESULTS The optimal cut-off values for CA125 and FAR were 9.88 and 0.0697, respectively, according to the receiver operating characteristic curve (ROC). Th area under the ROC curve of FCS is higher than CA125 and FAR. 330 patients were grouped into three groups according to the FCS. High FCS was related to males, anemia, tumor size, TNM stage, lymph node metastasis, tumor invasion depth, SII, and pathological subtypes. K-M analysis showed that high FCS and FAR were associated with poor survival. In the multivariate analysis, FCS, TNM stage, and SII were independent prognostic factors for poor OS in resectable GSRC patients. And the predictive accuracy of clinical nomogram contained FCS was better than TNM stage. CONCLUSION This study indicated that the FCS is a prognostic, and effective biomarker for patients with surgically resectable GSRC. Such developed FCS-based nomogram could be effective tools to assist the clinicians to determine the treatment strategy.
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Affiliation(s)
- Yimin Shen
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Yuanyuan Li
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Zhou Wang
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Wei Xu
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Wenjie Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China
| | - Xiao Chen
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China.
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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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Cruz D, Pinto Silva C, Marques C, Pereira FM, Leitão A, Ogando A. Lower Limb Edema Caused by Metastatic Signet Ring Cell Stomach Cancer. Eur J Case Rep Intern Med 2023; 10:003848. [PMID: 37680782 PMCID: PMC10482131 DOI: 10.12890/2023_003848] [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: 03/04/2023] [Accepted: 03/12/2023] [Indexed: 09/09/2023] Open
Abstract
Overall gastric cancer incidence is decreasing, but incidence of gastric signet ring cell carcinoma has been rising. The diagnosis can be challenging. It has a poorer prognosis because it tends to be diagnosed at advanced stages. Lymphedema is a rare presentation. We report a rare presentation of signet ring cell carcinoma in a 49-year old male, with no underlying medical condition. The patient presented with lymphedema of lower limbs, scrotum and abdominal wall. LEARNING POINTS Signet ring cell carcinoma tends to have an infiltrative behavior. Endoscopic analysis may not lead to any macroscopic finding.In highly suspicious cases, endoscopic exploration should be complemented with an endoscopic ultrasound or blind random biopsies.
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Affiliation(s)
- Dany Cruz
- Internal Medicine Department at Hospital Santa Maria Maior, Portugal
| | | | - Cristina Marques
- Internal Medicine Department at Hospital Santa Maria Maior, Portugal
| | | | - Alexandra Leitão
- Internal Medicine Department at Hospital Santa Maria Maior, Portugal
| | - Ana Ogando
- Internal Medicine Department at Hospital Santa Maria Maior, Portugal
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Lehnen N, Hallek M. [Sex-specific differences of special tumor diseases]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023; 64:717-726. [PMID: 37458764 PMCID: PMC10366284 DOI: 10.1007/s00108-023-01551-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/02/2023] [Indexed: 07/25/2023]
Abstract
BACKGROUND Numerous data show that sex and gender have gained increasing importance in precision medicine as relevant modulators of specific oncological and hematological diseases. The purpose of this article is to provide a summary of the current state of knowledge on sex differences in the incidence and outcome of specific malignancies and to further elucidate possible underlying causes. MATERIAL AND METHODS Evaluation and discussion of basic research studies, meta-analyses, and clinical trials. RESULTS There are significant sex-specific differences in the incidence, response rates, and mortality for a variety of oncological diseases. For the most part, men have poorer outcomes, whereas women have higher treatment-associated toxicities and distinct presentations at younger ages. Hormonal, immunological, and pharmacological causes are suspected. CONCLUSION Advanced patient-individualized treatment in oncology and hematology will be measured in the future by the implementation of the existing relevant sex differences in the clinical practice and further investigations on underlying mechanisms in studies in order to guarantee and to optimize the best possible treatment for oncological patients in the future.
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Affiliation(s)
- Nathalie Lehnen
- Klinik I für Innere Medizin, Universitätsklinikum Köln (AöR), Kerpener Str. 62, 50937, Köln, Deutschland.
| | - Michael Hallek
- Klinik I für Innere Medizin, Universitätsklinikum Köln (AöR), Kerpener Str. 62, 50937, Köln, Deutschland
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Graziosi L, Marino E, Natalizi N, Donini A. Prognostic Survival Significance of Signet Ring Cell (SRC) Gastric Cancer: Retrospective Analysis from a Single Western Center. J Pers Med 2023; 13:1157. [PMID: 37511770 PMCID: PMC10382060 DOI: 10.3390/jpm13071157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/07/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
INTRODUCTION Signet ring cell carcinoma accounts for 35% to 45% of all gastric cancer. Despite the acknowledgment of its more aggressive pathological features, various controversies surrounding this topic still exist. Thus, we investigate the clinical pathological characteristics and survival prognostic significance of signet ring cell components in patients affected by gastric cancer. METHODS From January 2004 to December 2020, in a retrospective study, we enrolled 404 patients with gastric cancer who were curatively treated in our department. The male-to-female ratio was 249/142, and the median age was 75 (range 37-94). We dichotomized patients into two groups (75 patients vs. 316 patients) based on the signet ring cell presence; according to preoperative, operative, and postoperative characteristics, we performed a univariate and multivariate analysis for overall survival. RESULTS Signet ring cell carcinoma indicated an increasing incidence trend over the time analyzed. Overall median survival of signet ring cell and non-signet ring cell carcinoma were, respectively, 16 vs. 35 months, p < 0.05. In early gastric cancer, the prognosis of the signet ring cell is better than that of the non-signet ring cell, as opposed to advanced cancer. Among the entire population in the multivariate analysis, the only independent factors were preoperative serum albumin level, complete surgical resection, level of lymphadenectomy, and pathological stage. Recurrence occurred more frequently in patients affected by signet ring cell, but in our data, we could not identify a peculiar site of recurrence. CONCLUSIONS Signet ring cell carcinoma has a specific oncogenetic phenotype and treatment resistance heterogeneity; however, it is not always associated with poor prognosis. According to our results, a radical surgical procedure associated with an adequate lymphadenectomy should be advocated to improve patients survival. Gastric cancer patients with signet ring cell components should draw clinicians' attention.
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Affiliation(s)
- Luigina Graziosi
- General and Emergency Surgery of Santa Maria della Misericordia Hospital, University of Perugia, 06132 Perugia, Italy
| | - Elisabetta Marino
- General and Emergency Surgery of Santa Maria della Misericordia Hospital, University of Perugia, 06132 Perugia, Italy
| | - Nicola Natalizi
- General and Emergency Surgery of Santa Maria della Misericordia Hospital, University of Perugia, 06132 Perugia, Italy
| | - Annibale Donini
- General and Emergency Surgery of Santa Maria della Misericordia Hospital, University of Perugia, 06132 Perugia, Italy
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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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Zhao W, Jia Y, Sun G, Yang H, Liu L, Qu X, Ding J, Yu H, Xu B, Zhao S, Xing L, Chai J. Single-cell analysis of gastric signet ring cell carcinoma reveals cytological and immune microenvironment features. Nat Commun 2023; 14:2985. [PMID: 37225691 DOI: 10.1038/s41467-023-38426-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 05/03/2023] [Indexed: 05/26/2023] Open
Abstract
Gastric signet ring cell carcinoma (GSRC) is a special subtype of gastric cancer (GC) associated with poor prognosis, but an in-depth and systematic study of GSRC is lacking. Here, we perform single-cell RNA sequencing to assess GC samples. We identify signet ring cell carcinoma (SRCC) cells. Microseminoprotein-beta (MSMB) can be used as a marker gene to guide the identification of moderately/poorly differentiated adenocarcinoma and signet ring cell carcinoma (SRCC). The upregulated differentially expressed genes in SRCC cells are mainly enriched in abnormally activated cancer-related signalling pathways and immune response signalling pathways. SRCC cells are also significantly enriched in mitogen-activated protein kinase and oestrogen signalling pathways, which can interact and promote each other in a positive feedback loop. SRCC cells are shown to have lower cell adhesion and higher immune evasion capabilities as well as an immunosuppressive microenvironment, which may be closely associated with the relatively poor prognosis of GSRC. In summary, GSRC exhibits unique cytological characteristics and a unique immune microenvironment, which may be advantageous for accurate diagnosis and treatment.
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Affiliation(s)
- Weizhu Zhao
- Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, China
- Department of Radialogy Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Department of Oncology, Binzhou People's Hospital Affiliated to Shandong First Medical University, Binzhou, Shandong, China
| | - Yanfei Jia
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, Shandong, China
| | - Guangyu Sun
- Department of Oncology, Binzhou People's Hospital Affiliated to Shandong First Medical University, Binzhou, Shandong, China
| | - Haiying Yang
- Department of Cardiology, Binzhou People's Hospital Affiliated to Shandong First Medical University, Binzhou, Shandong, China
| | - Luguang Liu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xianlin Qu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Jishuang Ding
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Hang Yu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Botao Xu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Siwei Zhao
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Ligang Xing
- Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, China.
- Department of Radialogy Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
| | - Jie Chai
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
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Chen C, Wang Z, Qin Y. Prognosis prediction in esophageal signet-ring-cell carcinoma: a competing risk analysis. BMC Gastroenterol 2023; 23:178. [PMID: 37221531 DOI: 10.1186/s12876-023-02818-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/13/2023] [Indexed: 05/25/2023] Open
Abstract
OBJECTIVE This study aims to construct and validate a competing risk nomogram model to predict 1-year, 3-year, and 5-year cancer-specific survival (CSS) for patients with esophageal signet-ring-cell carcinoma. METHODS Patients diagnosed with esophageal signet-ring-cell carcinoma (ESRCC) between 2010 and 2015 were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database. We performed the competing risk model to select significant variables to build a competing risk nomogram, which was used to estimate 1-year, 3-year, and 5-year CSS probability. The C-index, receiver operating characteristic (ROC) curve, calibration plot, Brier score, and decision curve analysis were performed in the internal validation. RESULTS A total of 564 patients with esophageal signet-ring-cell carcinoma fulfilled the eligibility criteria. The competing risk nomogram identified 4 prognostic variables, involving the gender, lung metastases, liver metastases, and receiving surgery. The C indexes of nomogram were 0.61, 0.75, and 0.70, respectively for 5-year, 3-year, and 1-year CSS prediction. The calibration plots displayed high consistency. The Brier scores and decision curve analysis respectively favored good prediction ability and clinical utility of the nomogram. CONCLUSIONS A competing risk nomogram for esophageal signet-ring-cell carcinoma was successfully constructed and internally validated. This model is expected to predict 1-year, 3-year, and 5-year CSS, and help oncologists and pathologists in clinical decision making and health care management for esophageal signet-ring-cell carcinoma patients.
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Affiliation(s)
- Chen Chen
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key, Zhengzhou University, Zhengzhou, China
| | - Zehua Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key, Zhengzhou University, Zhengzhou, China
| | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key, Zhengzhou University, Zhengzhou, China.
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Mantziari S, St Amour P, Abboretti F, Teixeira-Farinha H, Gaspar Figueiredo S, Gronnier C, Schizas D, Demartines N, Schäfer M. A Comprehensive Review of Prognostic Factors in Patients with Gastric Adenocarcinoma. Cancers (Basel) 2023; 15:cancers15051628. [PMID: 36900419 PMCID: PMC10000968 DOI: 10.3390/cancers15051628] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/25/2023] [Accepted: 03/02/2023] [Indexed: 03/09/2023] Open
Abstract
Gastric adenocarcinoma remains associated with a poor long-term survival, despite recent therapeutical advances. In most parts of the world where systematic screening programs do not exist, diagnosis is often made at advanced stages, affecting long-term prognosis. In recent years, there is increasing evidence that a large bundle of factors, ranging from the tumor microenvironment to patient ethnicity and variations in therapeutic strategy, play an important role in patient outcome. A more thorough understanding of these multi-faceted parameters is needed in order to provide a better assessment of long-term prognosis in these patients, which probably also require the refinement of current staging systems. This study aims to review existing knowledge on the clinical, biomolecular and treatment-related parameters that have some prognostic value in patients with gastric adenocarcinoma.
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Affiliation(s)
- Styliani Mantziari
- Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne (UNIL), 1015 Lausanne, Switzerland
- Correspondence: ; Tel.: +41-21-3141-111
| | - Penelope St Amour
- Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
| | - Francesco Abboretti
- Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
| | - Hugo Teixeira-Farinha
- Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne (UNIL), 1015 Lausanne, Switzerland
| | - Sergio Gaspar Figueiredo
- Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
| | - Caroline Gronnier
- Oeso-Gastric Surgery Unit, Department of Digestive Surgery, Magellan Center, Bordeaux University Hospital, 33600 Pessac, France
- Faculty of Medicine, Bordeaux Ségalen University, 33000 Bordeaux, France
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Nicolas Demartines
- Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne (UNIL), 1015 Lausanne, Switzerland
| | - Markus Schäfer
- Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne (UNIL), 1015 Lausanne, Switzerland
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Subasinghe D, Acott N, Mahesh PKB, Sivaganesh S, Munasinghe S, Kumarasinghe MP, Samarasekera DN, Lokuhetty MDS. Human epidermal growth factor receptor-2 gene expression positivity determined by silver in situ hybridization/immunohistochemistry methods and associated factors in a cohort of Sri Lankan patients with gastric adenocarcinoma: a prospective study. J Int Med Res 2023; 51:3000605231154403. [PMID: 36814374 PMCID: PMC9950620 DOI: 10.1177/03000605231154403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023] Open
Abstract
OBJECTIVE Positive human epidermal growth factor 2 (HER2) expression and its predictive clinicopathological features remain unclear in Sri Lankan gastric cancer (GC) patients. Here, we aimed to determine GC HER2 status predictors by analyzing associations between clinicopathological features and HER2 expression using immunohistochemistry (IHC) and silver in situ hybridization (SISH). METHODS During this 4-year prospective study, clinicopathological data were collected from participants in the National Hospital of Sri Lanka. HER2 IHC and SISH were performed using commercial reagents. Using chi-square tests, associations of HER2-IHC/SISH with clinicopathological features were analyzed. RESULTS Overall, 145 GC patients were included, 69 had gastrectomies and 76 had biopsies. Positive HER2 expression by IHC was associated with age <60 years, high T stage (assessed pathologically in resections and radiologically in biopsies), high nuclear grade, tumor necrosis, mitosis >5/high-power field, with additional perineural invasion and lymphovascular invasion in resections. These features, excluding lymphovascular invasion but including male sex, were associated with HER2 expression by SISH. CONCLUSIONS Age <60 years, high nuclear grade, tumor necrosis, and perineural invasion are associated factors of HER2 status. These could be used to triage GC patients for HER2 status testing in limited resource settings where IHC/SISH analysis is costly.
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Affiliation(s)
- Duminda Subasinghe
- Department of Surgery, Faculty of Medicine, University of
Colombo, University Surgical Unit, The National Hospital of Sri Lanka, Colombo,
Sri Lanka,PathWest Laboratory Medicine, Perth, & School of Pathology
and Laboratory Medicine, University of Western Australia, Perth, Australia,Duminda Subasinghe, Department of Surgery,
Faculty of Medicine, University of Colombo, University Surgical Unit, The
National Hospital of Sri Lanka, Colombo 00800, Sri Lanka.
| | - Nathan Acott
- PathWest Laboratory Medicine, Perth, & School of Pathology
and Laboratory Medicine, University of Western Australia, Perth, Australia
| | | | - Sivasuriya Sivaganesh
- Department of Surgery, Faculty of Medicine, University of
Colombo, University Surgical Unit, The National Hospital of Sri Lanka, Colombo,
Sri Lanka
| | - Sithum Munasinghe
- Translational Health Research Institute, Western Sydney
University, Campbelltown Campus, Campbelltown, New South Wales, Australia
| | - Mariyan Priyanthi Kumarasinghe
- PathWest Laboratory Medicine, Perth, & School of Pathology
and Laboratory Medicine, University of Western Australia, Perth, Australia
| | - Dharmabandu Nandaveva Samarasekera
- Department of Surgery, Faculty of Medicine, University of
Colombo, University Surgical Unit, The National Hospital of Sri Lanka, Colombo,
Sri Lanka
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Survival Outcome of Gastric Signet Ring Cell Carcinoma Based on the Optimal Number of Examined Lymph Nodes: A Nomogram- and Machine-Learning-Based Approach. J Clin Med 2023; 12:jcm12031160. [PMID: 36769809 PMCID: PMC9918112 DOI: 10.3390/jcm12031160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/27/2023] [Accepted: 01/29/2023] [Indexed: 02/05/2023] Open
Abstract
The optimal number of examined lymph nodes (ELNs) for gastric signet ring cell carcinoma recommended by National Comprehensive Cancer Network guidelines remains unclear. This study aimed to determine the optimal number of ELNs and investigate its prognostic significance. In this study, we included 1723 patients diagnosed with gastric signet ring cell carcinoma in the Surveillance, Epidemiology, and End Results database. X-tile software was used to calculate the cutoff value of ELNs, and the optimal number of ELNs was found to be 32 for adequate nodal staging. In addition, we performed propensity score matching (PSM) analysis to compare the 1-, 3-, and 5-year survival rates; 1-, 3-, and 5-year survival rates for total examined lymph nodes (ELNs < 32 vs. ELNs ≥ 32) were 71.7% vs. 80.1% (p = 0.008), 41.8% vs. 51.2% (p = 0.009), and 27% vs. 30.2% (p = 0.032), respectively. Furthermore, a predictive model based on 32 ELNs was developed and displayed as a nomogram. The model showed good predictive ability performance, and machine learning validated the importance of the optimal number of ELNs in predicting prognosis.
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Effects of Tumor Localization, Age, and Stage on the Outcomes of Gastric and Colorectal Signet Ring Cell Adenocarcinomas. Cancers (Basel) 2023; 15:cancers15030714. [PMID: 36765680 PMCID: PMC9913295 DOI: 10.3390/cancers15030714] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/17/2023] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
Signet ring cell adenocarcinomas (SRCCs) are a rare histological adenocarcinoma subtype, classically thought to have a worse prognosis than conventional adenocarcinomas. The majority of these cancers occur in the stomach, colon, and rectum. Their rarity means that most epidemiological studies into their pathology are often underpowered, and interpretations from these reports are mixed. In this study, we use the Surveillance, Epidemiology, and End Results Program (SEER) database to examine the effects of tumor localization, age, and stage on gastric and colorectal cancer outcomes. For early onset localized and regional gastric cancers, SRCCs have the same overall risk of mortality compared to conventional adenocarcinomas. Over the age of 50 years, SRCCs have worse outcomes across all stages. Gastric SRCCs are 2-3-fold more likely in younger patients, and more heavily favor the distal stomach. Like conventional adenocarcinomas, proximal gastric SRCCs have decreased survival. Across all ages, stages, and locations, colorectal SRCCs have worse outcomes. SRCCs favor the right colon, but outcomes are significantly worse for the left colon and rectal cancers. Relative to adenocarcinomas, colorectal SRCCs have the worst outcomes in younger patients. Overall, these results provide insights into SRCC disease patterns that cannot be surmised outside of population-level data.
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Epidemiology and Characteristics of Gastric Carcinoma in Childhood-An Analysis of Data from Population-Based and Clinical Cancer Registries. Cancers (Basel) 2023; 15:cancers15010317. [PMID: 36612313 PMCID: PMC9818931 DOI: 10.3390/cancers15010317] [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: 11/25/2022] [Revised: 12/29/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023] Open
Abstract
(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz−Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments.
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Xu J, Zhu J, Lin L, Li Z, Gu F, Wang F, Zhai H. Endoscopic and clinicopathologic features of early gastric signet ring cell carcinoma ≤20 mm: a retrospective observational study. Scand J Gastroenterol 2023; 58:38-44. [PMID: 35850581 DOI: 10.1080/00365521.2022.2100227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Limited literature exists on the characteristics of early gastric signet ring cell carcinoma (GSRCC) within 20 mm. This study aimed to explore this type of cancer from several aspects, to provide guidance for early detection and intervention of GSRCC. METHODS We retrospectively collected data from 24 patients diagnosed with early GSRCC ≤20 mm in Beijing Friendship Hospital from 2016 to 2021. According to tumor size, those lesions were divided into three groups: diminutive group (1-5 mm, n = 4), small group (6-10 mm, n = 12) and intermediate group (11-20 mm, n = 8). The clinicopathologic and endoscopic characteristics of GSRCC were compared among the three groups. RESULTS Treatment strategies for lesions differed according to the size (p<.05). There were no significant differences among the three groups with regard to age, sex, Helicobacter pylori infection, tumor location and macroscopic type. Lesions were often flat type and more likely to present with discoloration, uneven color, ulceration and submucosal invasion with the increase of diameter. Almost all cases showed abnormal intervening part (IP) under magnifying endoscopy. CONCLUSIONS The location of early signet ring cell carcinoma is not specific, and the diminutive lesions are often flat. Abnormal IP may be the early endoscopic feature of early GSRCC.
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Affiliation(s)
- Jianing Xu
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Jingyi Zhu
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Lanhui Lin
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Zhiyu Li
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Feng Gu
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Fangning Wang
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Huihong Zhai
- Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
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Corredor-Orlandelli D, Vargas L. Lymphangitic carcinomatosis as the initial manifestation of primary signet-ring cell adenocarcinoma of the lung: A case report. Rare Tumors 2023; 15:20363613231164017. [PMID: 36937819 PMCID: PMC10014970 DOI: 10.1177/20363613231164017] [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: 08/03/2022] [Accepted: 02/28/2023] [Indexed: 03/15/2023] Open
Abstract
Signet-ring cell carcinomas are an aggressive, poorly differentiated, and highly invasive adenocarcinoma carrying a poor prognosis. Most of these tumors originate in gastrointestinal organs; however, primary lung signet-ring cell adenocarcinomas can rarely occur. Tumoral lymphatic infiltration is a complication of these tumors and can cause phenomena such as lymphangitic carcinomatosis, characterized by a nodular thickening of the pleura, pleural effusions, and mediastinal lymphadenopathies. We report a case of a 63-year-old ex-smoker with a 2-week clinical course of dyspnea and pleuritic chest pain in which a nodular thickening of the pleura and pleural effusion were documented and led to the diagnosis of a primary signet-ring cell adenocarcinoma of the lung with lymphangitic carcinomatosis. This complication has never been described in the context of a primary lung tumor of this subtype. Both entities carry a high mortality and have no therapeutical options. This report adds to the information available about them.
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Affiliation(s)
- David Corredor-Orlandelli
- School of Medicine and Health
Sciences, Universidad del Rosario, Bogotá, Colombia
- David Corredor-Orlandelli, School of
Medicine and Health Sciences, Universidad del Rosario, Carrera 24 #63C-69,
Bogotá 110111, Colombia.
| | - Lina Vargas
- Internal Medicine Department, Fundación Cardioinfantil -
LaCardio, Bogotá, Colombia
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Çağlar R. The relationship of different preoperative inflammatory markers with the prognosis of gastric carcinoma. Asian J Surg 2023; 46:360-365. [PMID: 35589478 DOI: 10.1016/j.asjsur.2022.04.075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 03/15/2022] [Accepted: 04/21/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND It is aimed to determine the prognostic values of preoperative inflammatory biomarkers in patients undergoing curative surgery for gastric carcinoma and to contribute to the development of prognostic modeling. OBJECTIVE To investigate the effect of various different preoperative inflammatory markers on the prognosis of gastric carcinoma. MATERIAL AND METHOD The medical data and the mortality status of 91 patients who underwent total or subtotal gastrectomy operation for gastric carcinoma at Mersin City Training and Research Hospital between 2016 and 2020 were retrospectively reviewed from the hospital records and patient files. The patients' demographic characteristics, tumor location, histopathological diagnosis, pathological stage, tumor markers, and preoperative inflammatory and hematological markers were analyzed. Based on these data, tumor stage, metastatic lymph node ratio (MLR), lactate dehydrogenase albumin ratio (LAR), neutrophil-lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) were calculated. The relationship between these parameters and postoperative survival was analyzed. Statistical analyses were performed with IBM SPSS for Windows, version 17.0 (IBM Corporation, Armonk, New York, United States). RESULTS The correlation analysis of the parameters affecting survival showed that, in addition to an advanced tumor stage, inflammatory parameters like NLR, PLR, and LAR adversely affected survival. CONCLUSION Preoperative NLR, PLR, LAR, and advanced tumor stage may help determine the survival of gastric carcinoma patients. Multiple studies with larger series are needed on this subject.
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Affiliation(s)
- Recep Çağlar
- Mersin City Training and Research Hospital, Department of General Surgery/ Gastroenterological Surgery, Mersin, Turkey.
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Huang J, Wang H, Xu Y, Li C, Lv X, Han X, Chen X, Chen Y, Yu Z. The Role of CTNNA1 in Malignancies: An Updated Review. J Cancer 2023; 14:219-230. [PMID: 36741258 PMCID: PMC9891874 DOI: 10.7150/jca.79236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 12/15/2022] [Indexed: 01/04/2023] Open
Abstract
Catenin alpha 1 (CTNNA1), encoding α-catenin, is involved in several physiological activities, such as adherens junction synthesis and signal transduction. Recent studies have suggested additional functions for CTNNA1 malignancies. This review systematically summarizes the varying functions of CTNNA1 in different tumors and briefly describes the diverse pathways and mechanisms involved in different types of tumors. CTNNA1 is abnormally expressed in leukemia and solid tumor such as cancers of digestive system, genitourinary system and breast, and it's related to the occurrence, development, and prognosis of tumors. In addition, the possible physiological processes involving CTNNA1, such as methylation, miRNA interference, or regulatory axes, similar to those of CDH1, SETD2, and hsa-miR-30d-5p/GJA1 are also summarized here. The precise mechanism of CTNNA1 in most cancers remains uncertain; hence, additional pre-clinical studies of CTNNA1 are warranted for potential early tumor diagnosis, prognosis, and treatment.
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Affiliation(s)
- Jinhua Huang
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China.,College of Medicine, Shantou University, Shantou, 515041, Guangdong, China
| | - Huihui Wang
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230023, China
| | - Yuting Xu
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China.,College of Medicine, Shantou University, Shantou, 515041, Guangdong, China
| | - Chunhua Li
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China
| | - Xinyue Lv
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China
| | - Xintong Han
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China
| | - Xiaochun Chen
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China
| | - Yu Chen
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China
| | - Zhiying Yu
- Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China.,✉ Corresponding author: Zhiying Yu, Shenzhen Second People's Hospital, 3002 Sungang West Road, Shenzhen, Guangdong, China, 518035. Tel: 0755-83366388; Fax: +86 83366388-3048; E-mail:
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Di L, Wu X, Tuo B. Endoscopic and pathohistologic features of early gastric signet ring cell carcinoma presented as elevated type: A case report. Front Oncol 2022; 12:1015989. [PMID: 36568238 PMCID: PMC9772830 DOI: 10.3389/fonc.2022.1015989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 11/21/2022] [Indexed: 12/14/2022] Open
Abstract
Background Almost all early gastric signet ring cell carcinomas (SRCCs) are the flat or depressed type, and the elevated type is rare. Here, we report the endoscopic and pathohistologic features of a rare case of SRCCs presented as the elevated type. Case presentation A 54-year-old man underwent esophagogastroduodenoscopy in our hospital because of intermittent upper abdominal pain for 6 years. White light endoscopy revealed an elevated lesion that is smooth and reddish and covered with normal mucosa and looked like a polyp. Magnifying endoscopy with narrow-band imaging showed broadened intervening parts, an elongated pit, and a dense microvascular network with focal irregularity. The lesion was considered as early gastric cancer and completely resected with endoscopic submucosal dissection. Pathohistological examination confirmed that the lesion was pure early SRCC that was limited within the mucosal lamina propria (T1a). Conclusion Elevated pure gastric SRCC is rare. This is a report of early pure gastric SRCC presented as the elevated type and the description of its endoscopic and pathohistologic features, which will contribute to the early detection of gastric SRCC.
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Affiliation(s)
- Lianjun Di
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xinglong Wu
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Biguang Tuo
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China,*Correspondence: Biguang Tuo,
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Yu X, Chen Y, Lu J, He K, Chen Y, Ding Y, Jin K, Wang H, Zhang H, Wang H, Teng L. Patient-derived xenograft models for gastrointestinal tumors: A single-center retrospective study. Front Oncol 2022; 12:985154. [PMID: 36465411 PMCID: PMC9716308 DOI: 10.3389/fonc.2022.985154] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 10/28/2022] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Patient-derived xenograft (PDX) models have shown a great efficiency in preclinical and translational applications. Gastrointestinal (GI) tumors have a strong heterogeneity, and the engraftment rate of PDX models remarkably vary. However, the clinicopathological and molecular characteristics affecting the engraftment rate still remain elusive. METHODS A total of 312 fresh tumor tissue samples from patients with GI cancer were implanted into immunodeficient mice. The median follow-up time of patients was 37 months. Patients' characteristics were compared in terms of PDX growth and overall survival. PDX models of 3-6 generations were used for drug evaluation. RESULTS In total, 171 (54.8%, 171/312) PDX models were established, including 85 PDX models of colorectal cancer, 21 PDX models of esophageal cancer, and 65 PDX models of gastric cancer. Other than tumor site, histology, differentiation degree, and serum alpha-fetoprotein (AFP) level, no significant differences were found between transplantation of xenografts and patients' characteristics. For patients who had undergone neoadjuvant therapy, the incidence of tumor formation was higher in those with progressive disease (PD) or stable disease (SD). In gastric cancer, the results showed a higher transplantation rate in deficient mismatch repair (dMMR) tumors, and Ki-67 could be an important factor affecting the engraftment rate. The gene mutation status of RAS and BRAF, two important molecular markers in colorectal cancer, showed a high degree of consistency between patients' tumors and PDXs. However, no significant effects of these two mutations on PDX engraftment rate were observed. More importantly, in this study although KRAS mutations were detected in two clinical cases, evident tumor inhibition was still observed after cetuximab treatment in both PDX models and patients. CONCLUSION A large-scale PDX model including 171 cases was successfully established for GI tumors in our center. The relationship between clinicopathological and molecular features and engraftment rates were clarified. Furthermore, this resource provides us with profound insights into tumor heterogeneity, making these models valuable for PDX-guided treatment decisions, and offering the PDX model as a great tool for personalized treatment and translation research.
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Affiliation(s)
- Xiongfei Yu
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yiran Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jun Lu
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Kuifeng He
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yanyan Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yongfeng Ding
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Ketao Jin
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Haiyong Wang
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Haibin Zhang
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Haohao Wang
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Lisong Teng
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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Chen Y, Chen Y, Wen L, Tou L, Wang H, Teng L. PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study. Front Surg 2022; 9:986696. [PMID: 36439539 PMCID: PMC9684711 DOI: 10.3389/fsurg.2022.986696] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 10/24/2022] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND The clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC. METHODS Among 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis. RESULTS Borrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis. CONCLUSIONS Borrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.
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Affiliation(s)
- Yiran Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yanyan Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Liping Wen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Laizhen Tou
- Department of Gastrointestinal Surgery, Lishui Hospital, College of Medicine, Zhejiang University, Lishui, China
| | - Haiyong Wang
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lisong Teng
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Tavakkoli A, Pruitt SL, Hoang AQ, Zhu H, Hughes AE, McKey TA, Elmunzer BJ, Kwon RS, Murphy CC, Singal AG. Ethnic Disparities in Early-Onset Gastric Cancer: A Population-Based Study in Texas and California. Cancer Epidemiol Biomarkers Prev 2022; 31:1710-1719. [PMID: 35732290 PMCID: PMC9444918 DOI: 10.1158/1055-9965.epi-22-0210] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/04/2022] [Accepted: 06/15/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Incidence rates of gastric cancer are increasing in young adults (age <50 years), particularly among Hispanic persons. We estimated incidence rates of early-onset gastric cancer (EOGC) among Hispanic and non-Hispanic White persons by census tract poverty level and county-level metro/nonmetro residence. METHODS We used population-based data from the California and Texas Cancer Registries from 1995 to 2016 to estimate age-adjusted incidence rates of EOGC among Hispanic and non-Hispanic White persons by year, sex, tumor stage, census tract poverty level, metro versus nonmetro county, and state. We used logistic regression models to identify factors associated with distant stage diagnosis. RESULTS Of 3,047 persons diagnosed with EOGC, 73.2% were Hispanic White. Incidence rates were 1.29 [95% confidence interval (CI), 1.24-1.35] and 0.31 (95% CI, 0.29-0.33) per 100,000 Hispanic White and non-Hispanic White persons, respectively, with consistently higher incidence rates among Hispanic persons at all levels of poverty. There were no statistically significant associations between ethnicity and distant stage diagnosis in adjusted analysis. CONCLUSIONS There are ethnic disparities in EOGC incidence rates that persist across poverty levels. IMPACT EOGC incidence rates vary by ethnicity and poverty; these factors should be considered when assessing disease risk and targeting prevention efforts.
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Affiliation(s)
- Anna Tavakkoli
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas,Department of Population and Data Sciences, University of Texas Southwestern, Dallas, Texas,Simmons Comprehensive Cancer Center, University of Texas Southwestern, Dallas, Texas
| | - Sandi L Pruitt
- Department of Population and Data Sciences, University of Texas Southwestern, Dallas, Texas,Simmons Comprehensive Cancer Center, University of Texas Southwestern, Dallas, Texas
| | - Anh Q. Hoang
- Natural Sciences and Mathematics, The University of Texas at Dallas, Dallas, Texas
| | - Hong Zhu
- Simmons Comprehensive Cancer Center, University of Texas Southwestern, Dallas, Texas
| | - Amy E Hughes
- Department of Population and Data Sciences, University of Texas Southwestern, Dallas, Texas,Simmons Comprehensive Cancer Center, University of Texas Southwestern, Dallas, Texas
| | - Thomas A. McKey
- Department of Population and Data Sciences, University of Texas Southwestern, Dallas, Texas
| | - B. Joseph Elmunzer
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Richard S. Kwon
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Caitlin C. Murphy
- School of Public Health, University of Texas Health Science Center at Houston, Houston, TX
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas,Department of Population and Data Sciences, University of Texas Southwestern, Dallas, Texas,Simmons Comprehensive Cancer Center, University of Texas Southwestern, Dallas, Texas
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Predictors of Long-Time Survivors in Nonmetastatic Colorectal Signet Ring Cell Carcinoma: A Large Population-Based Study. Gastroenterol Res Pract 2022; 2022:5393571. [PMID: 36032271 PMCID: PMC9402301 DOI: 10.1155/2022/5393571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 07/12/2022] [Indexed: 11/18/2022] Open
Abstract
Background Colorectal signet ring cell carcinoma (SRCC) is a rare and distinct subtype of colorectal cancer (CRC), with extremely poor prognosis and aggressive tumor biological behavior. In this study, we aimed to analyze the clinicopathological characteristics and to identify the independent predictors of long-time survivors (LTSs) of nonmetastatic colorectal SRCC. Methods Patients diagnosed with nonmetastatic colorectal SRCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared and analyzed the clinicopathological characteristics between LTSs (patients survived over 5 years) and non-LTSs (patients survived of or less than 5 years). Afterwards, multivariate logistic regression analysis was used to identify independent predictors of LTSs, which were further used to construct a nomogram model to predict the probability of being LTSs. Results We enrolled 2050 patients with nonmetastatic colorectal SRCC, consisting of 1441 non-LTSs and 609 LTSs. Multivariate logistic regression analysis revealed that race, marital status, tumor infiltration, lymph node involvement, and primary tumor treatment were independent predictors of LTSs. In addition, these five parameters were incorporated into a nomogram model to predict the probability of being LTSs. In terms of the model performance, the calibration curve revealed good agreement between observed and predicted probability of LTSs, and receiving operator characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. Conclusion Collectively, we analyzed and profiled the clinicopathological characteristics of LTSs in patients with nonmetastatic colorectal SRCC. Race, marital status, T stage, N stage, and primary tumor treatment were independent predictors of LTSs.
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Drubay V, Nuytens F, Renaud F, Adenis A, Eveno C, Piessen G. Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management. World J Gastrointest Oncol 2022; 14:1406-1428. [PMID: 36160745 PMCID: PMC9412924 DOI: 10.4251/wjgo.v14.i8.1406] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 05/08/2022] [Accepted: 07/17/2022] [Indexed: 02/05/2023] Open
Abstract
While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.
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Affiliation(s)
- Vincent Drubay
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- Department of Digestive Surgery, Cambrai Hospital Center and Sainte Marie, Group of Hospitals of The Catholic Institute of Lille, Cambrai 59400, France
| | - Frederiek Nuytens
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, AZ Groeninge Hospital, Kortrijk 8500, Belgium
| | - Florence Renaud
- Department of Pathology, University Lille Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
| | - Antoine Adenis
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
- Department of Medical Oncology, Montpellier Cancer Institute, Monpellier 34000, France
- IRCM, Inserm, University of Monpellier, Monpellier 34000, France
| | - Clarisse Eveno
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
- FREGAT Network, Claude Huriez University Hospital, Lille 59000, France
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Guo Y, Wang Q, Tian Q, Bo C, Li N, Zhang S, Li P. Clinicopathological Features and Prognostic-Related Risk Factors of Gastric Signet Ring Cell Carcinoma: A Meta-Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3473445. [PMID: 36035278 PMCID: PMC9410921 DOI: 10.1155/2022/3473445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/06/2022] [Accepted: 07/17/2022] [Indexed: 11/23/2022]
Abstract
Background Gastric signet ring cell carcinoma (SRCC) has shown a growth growing trend worldwide, but its clinicopathological features and prognostic-related risk factors have not been systematically studied. This systematic review was devoted to this. Method PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved, and retrospective cohort studies comparing clinicopathological features and related risk factors in SRCC patients were included. Results In SRCC patient population, males were more than females (male, OR = 1.38, 95% CI: 1.20-1.60); N3 patients were more than N0-2 patients (N0-2, OR = 3.19, 95% CI: 1.98-5.15); M1 patients were more than M0 patients (M0, OR = 3.30, 95% CI: 1.88-5.80); patients with tumor > 5 cm were more than those with tumor (≤5 cm, OR = 7.36, 95% CI: 1.33-40.60). Patients with age < 60 years (age ≥ 60 years, OR = 1.03, 95% CI: 1.01-1.05), lymphatic vessel invasion (no, OR = 1.74, 95% CI: 1.03-2.45), T2 (T1, OR = 1.17, 95% CI: 1.07-1.28) and T4 (T1, OR = 2.55, 95% CI: 2.30-2.81) stages, and N1 (N0, OR = 1.73, 95% CI: 1.08-2.38), N2 (N0, OR = 2.24, 95% CI: 1.12-3.36), and N3 (N0, OR = 3.45, 95% CI: 1.58-5.32) stages had higher hazard ratio (HR). Conclusion SRCC may occur frequently in male. Age, lymphatic vessel invasion, TN, and M stage may be risk factors for poor prognoses of SRCC patients.
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Affiliation(s)
- Ying Guo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qian Wang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qing Tian
- Thoracic Surgery Department, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Changwen Bo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Na Li
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Sujing Zhang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Peishun Li
- Department of Oncology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, China
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Zaafouri H, Jouini R, Khedhiri N, Khanchel F, Cherif M, Mesbahi M, Daghmouri A, Mahmoudi W, Akremi S, Sabbah M, Benzarti Y, Hadded D, Gargouri D, Bader MB, Maamer AB. Comparison between signet-ring cell carcinoma and non-signet-ring cell carcinoma of the stomach: clinicopathological parameters, epidemiological data, outcome, and prognosis-a cohort study of 123 patients from a non-endemic country. World J Surg Oncol 2022; 20:238. [PMID: 35858903 PMCID: PMC9297662 DOI: 10.1186/s12957-022-02699-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 06/29/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Signet-ring cell carcinoma of the stomach (SRCC) is a particular gastric cancer entity. Its incidence is increasing. Its diagnosis is pathological; it corresponds to adenocarcinoma with a majority of signet-ring cells component (> 50%). These histological features give it its aggressiveness characteristics. This has repercussions on the prognostic level and implications for the alternatives of therapy, especially since some authors suggest a potential chemoresistance. This survey aimed to identify the epidemiological, pathological, therapeutic, and prognostic characteristics of SRCC as a separate disease entity. METHODS This was a retrospective study of 123 patients admitted for gastric adenocarcinoma to Habib Thameur Hospital in Tunis over 11 years from January 2006 to December 2016. A comparative study was performed between 2 groups: the SRCC group with 62 patients and the non-SRCC (non-signet-ring cell carcinoma of the stomach) with 61 patients. RESULTS The prevalence of SRCC in our series was 50%. SRCC affected significantly younger patients (55 vs 62 years; p = 0.004). The infiltrative character was more common in SRCC tumors (30.6 vs 14.8%; p = 0.060), whereas the budding character was more often noted in non-SRCC tumors (78.7 vs 58.1%; p = 0.039). There was no significant difference in tumor localization between both groups. Linitis plastica was noted in 14 patients with SRCC against a single patient with non-SRCC (p = 0.001). The tumor size was more important in the non-SRCC group (6.84 vs 6.39 cm; p = 0.551). Peritoneal carcinomatosis was noted in 4.3% of cases in the SRCC group versus 2.2% of cases in the NSRCC group (p = 0.570). Total gastrectomy was more often performed in the SRCC group (87 vs 56%; p = 0.001). Resection was more often curative in the non-SRCC group (84.4 vs 78.3%; p = 0.063). Postoperative chemotherapy was more commonly indicated in the SRCC group (67.4 vs 53.3%; p = 0.339). Tumor recurrence was more common in the non-SRCC group (35.7 vs 32%; p = 0.776). The most common type of recurrence was peritoneal carcinomatosis in the SRCC group (62.5%) and hepatic metastasis in the non-SRCC group (60%; p = 0.096). The overall 5-year survival in the SRCC group was lower than in the non-SRCC group, with no statistically significant difference (47.1 vs 51.5%; p = 0.715). The overall survival was more important for SRCC in early cancer (100 vs 80%; p = 0.408), whereas it was higher for non-SRCC in advanced cancer (48.1 vs 41.9%; p = 0.635). CONCLUSION Apart from its epidemiological and pathological features, SRCC seems to have a worse prognosis. Indeed, it is diagnosed at a more advanced stage and has a worse prognosis in advanced cancer than non-SRCC. It is therefore to be considered as a particular entity of gastric adenocarcinoma requiring a specific therapeutic protocol where the place of chemotherapy remains to be more investigated.
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Affiliation(s)
- Haithem Zaafouri
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia.
| | - Raja Jouini
- Department of Cytopathology, Habib Thameur Hospital, Tunis, Tunisia
| | - Nizar Khedhiri
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Fatma Khanchel
- Department of Cytopathology, Habib Thameur Hospital, Tunis, Tunisia
| | - Mona Cherif
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Meryam Mesbahi
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Aziz Daghmouri
- Department of Anesthesiology, Habib Thameur Hospital, Tunis, Tunisia
| | - Wiem Mahmoudi
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Soumaya Akremi
- Department of Anesthesiology, Habib Thameur Hospital, Tunis, Tunisia
| | - Meriam Sabbah
- Department of Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia
| | - Yazid Benzarti
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Dhafer Hadded
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Dalila Gargouri
- Department of Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia
| | - Mourad Ben Bader
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Anis Ben Maamer
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
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