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Núñez JC, Rivera MT, Stevens MA. Adenocarcinoma of the duodenal papilla with synchronous peritoneal metastases-5 years of overall survival: A case report. World J Clin Oncol 2025; 16:103651. [DOI: 10.5306/wjco.v16.i4.103651] [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: 11/25/2024] [Revised: 12/20/2024] [Accepted: 02/08/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Ampullary adenocarcinomas are a rare disease. They can be classified anatomically or according to their histology into intestinal, pancreatobiliary, and mixed subtypes, with different subtypes having distinct prognoses and potential treatments. We report a clinical case of a patient with mixed type adenocarcinoma of the ampulla of Vater, with predominantly intestinal histology, associated with an isolated and synchronous peritoneal carcinomatosis. It is the only case reported in the literature of duodenal ampulla cancer with synchronous peritoneal metastases, with long-term survival.
CASE SUMMARY A 53-year-old male patient with non-insulin-dependent diabetes presented with acute abdominal pain in the right hypochondrium. Images revealed dilatation of the biliary tract and the duct of Wirsung, without a clear obstructive factor. Upper gastrointestinal endoscopy revealed a tumor in the duodenal papilla. Biopsies confirmed an adenocarcinoma. In the first surgical step, a biliodigestive bypass was performed in association with resection of the carcinomatosis. Peritoneal metastases was found during the intraoperative period. Subsequently, chemotherapy with the folinic acid, fluorouracil, and oxaliplatin regimen was administered based on histology, and a favorable response was achieved. After a multidisciplinary discussion, the Whipple procedure was performed. A delayed biopsy showed disease-free margins. The patient achieved 5 years of overall survival in August 2024, and 4 years of disease-free survival in September 2024.
CONCLUSION We conclude that an important value of this work is showing individualized treatment for a patient with cancer.
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Affiliation(s)
- Julio César Núñez
- Department of Surgery, Hospital del Salvador, Santiago 7500922, Región Metropolitana, Chile
- Department of Surgery, Clínica Dávila-Vespucio, Santiago 8241479, Región Metropolitana, Chile
| | - María Teresa Rivera
- Department of Anatomic Pathology, Hospital del Salvador, Santiago 7500922, Región Metropolitana, Chile
| | - Mary Ann Stevens
- Department of Medical Oncology, Hospital del Salvador, Santiago 7500922, Región Metropolitana, Chile
- Department of Medical Oncology, Clínica Alemana, Santiago 7650568, Región Metropolitana, Chile
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Ou H, Zhuang J, Jian M, Zheng X, Wu T, Cheng H, Qian R. Perioperative versus adjuvant chemotherapy for resectable gastric cancer: a meta-analysis of randomized controlled trials. Front Oncol 2025; 15:1432596. [PMID: 40115020 PMCID: PMC11922704 DOI: 10.3389/fonc.2025.1432596] [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: 05/14/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
Objectives To report the latest systematic review and meta-analysis of randomized controlled trials (RCT) to compare perioperative versus adjuvant chemotherapy for resectable gastric cancer. Methods We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2024 for RCT which compared perioperative versus adjuvant chemotherapy for resectable gastric cancer. Outcomes measured were overall survival (OS) and progression-free survival (PFS). Results 5 RCTs including 2,735 patients were included for meta-analysis. Meta-analysis revealed a significant longer PFS in the neoadjuvant chemotherapy (NAC) group (HR: 0.77; 95% CI: 0.69, 0.85; P<0.00001) compared with adjuvant chemotherapy (AC) group. Subgroup analysis found that there was still a significant superiority of NAC in female (HR: 0.53; 95% CI: 0.40, 0.70; P<0.0001) and cN+ (HR: 0.77; 95% CI: 0.67, 0.89; P=0.0005) patients, while the superiority disappeared in male (HR: 0.87; 95% CI: 0.74, 1.01; P=0.07) and cN- patients (HR: 0.91; 95% CI: 0.46, 1.78; P=0.77). In addition, meta-analysis observed a trend towards improved OS with NAC (HR: 0.86; 95% CI: 0.70, 1.07; P = 0.17), and sensitivity analysis demonstrated instability in OS. Conclusions NAC can significantly prolong PFS in patients with resectable gastric cancer compared to AC, and the benefit is more significant in women and cN+ patients. Besides, our analysis indicated that NAC has a potential to improve OS compared with AC. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024546165.
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Affiliation(s)
- Haiya Ou
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Jiamei Zhuang
- Department of Nephrology, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Mingwei Jian
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xinyi Zheng
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Tingping Wu
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Honghui Cheng
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Rui Qian
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
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Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Wang Y, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E J, Ying X, Yao C, Shen L, Ji J. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): final report of a randomised, open-label, phase 3 trial. Lancet Oncol 2025; 26:312-319. [PMID: 39952264 DOI: 10.1016/s1470-2045(24)00676-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/21/2024] [Accepted: 11/22/2024] [Indexed: 02/17/2025]
Abstract
BACKGROUND The multicentre RESOLVE trial examined the efficacy of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in gastric or gastro-oesophageal junction cancer. Initial analyses did not encompass overall survival owing to the immature data. This paper provides an updated analysis of the survival data from the RESOLVE trial. METHODS In this randomised, open-label, phase 3 study, participants aged 18 years or older with cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma who were feasible for D2 lymphadenectomy and had a Karnofsky performance score of 70 or higher were enrolled. Participants were randomly assigned in a 1:1:1 ratio via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral capecitabine 1000 mg/m2 twice a day on days 1-14, adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day on days 1-14), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy. The primary endpoint, assessed in the modified intention-to-treat population, was 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-CapOx and the non-inferiority (hazard ratio [HR] non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx, and has been reported previously. This final report focuses on the secondary endpoint of 5-year overall survival, also assessed in the modified intention-to-treat population. Other secondary endpoints-R0 resection rate and safety-were not updated in this analysis. The study is registered at ClinicalTrials.gov, NCT01534546, and is complete. FINDINGS Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were enrolled and randomly assigned, of whom 1022 participants were included in the modified intention-to-treat population: 345 (259 male, 86 female) in the adjuvant-CapOx group, 340 (238 male, 102 female) in the adjuvant-SOX group, and 337 (271 male, 66 female) in the perioperative-SOX group. As of April 7, 2022, the median duration of follow-up was 62·8 months (IQR 52·0-75·1). The 5-year overall survival rates were 52·1% (95% CI 46·3-57·5) for the adjuvant-CapOx group, 61·0% (55·3-66·2) for the adjuvant-SOX group, and 60·0% (54·2-65·3), for the perioperative-SOX group. Overall survival was significantly prolonged with perioperative-SOX (HR 0·79; 95% CI 0·62-1·00, p=0·049) and adjuvant-SOX (HR 0·77, 0·61-0·98, p=0·033), compared with adjuvant-CapOx. INTERPRETATION Consistent with the initial analysis of 3-year disease-free survival, the extended 5-year overall survival analysis from the RESOLVE trial confirmed the survival advantage of perioperative-SOX and adjuvant-SOX compared with the standard adjuvant-CapOx regimen. The SOX regimen, given perioperatively or as an adjuvant treatment, emerges as a potential standard treatment modality for locally advanced gastric or gastro-oesophageal junction cancer management in Asian patients. FUNDING The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, the Beijing Natural Science Foundation, National Natural Science Foundation of China, the Beijing Natural Science Foundation, Taiho, Hengrui Pharmaceutical and Sanofi-Aventis. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
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Affiliation(s)
- Xiaotian Zhang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Han Liang
- Department of Abdominal Oncology Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yingwei Xue
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yanong Wang
- Department of Stomach Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jiren Yu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhaode Bu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lin Chen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China; Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yian Du
- Department of General Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xinbao Wang
- Department of Hepatopancreatobiliary Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Aiwen Wu
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Guoli Li
- Department of General Surgery, Jinling Hospital, Nanjing, China
| | - Xiangqian Su
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Gang Xiao
- Department of General Surgery, Beijing Hospital, Beijing, China
| | - Ming Cui
- Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Dan Wu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Li Chen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China; Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaojiang Wu
- Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yanbing Zhou
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lianhai Zhang
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Chengxue Dang
- Department of Oncology Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yulong He
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Li
- Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Huanqiu Chen
- Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, China
| | - Yuxian Bai
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yakun Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Peiwu Yu
- Department of General Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Guanbao Zhu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jian Suo
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Baoqing Jia
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Jinan, China
| | - Changming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital Capital Medical University, Beijing, China
| | - Yingjiang Ye
- Department of General Surgery, Peking University People's Hospital, Beijing, China
| | - Huimian Xu
- Department of Gastrointestinal Oncology Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Xin Wang
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Yannan Yuan
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jianyu E
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Xiangji Ying
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Chen Yao
- Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China
| | - Lin Shen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Jiafu Ji
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China.
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Liu Y, Bian B, Chen S, Zhou B, Zhang P, Shen L, Chen H. Identification and Validation of Four Serum Biomarkers With Optimal Diagnostic and Prognostic Potential for Gastric Cancer Based on Machine Learning Algorithms. Cancer Med 2025; 14:e70659. [PMID: 40084401 PMCID: PMC11907202 DOI: 10.1002/cam4.70659] [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: 10/23/2024] [Revised: 01/20/2025] [Accepted: 01/26/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is considered a highly heterogeneous disease, and currently, a comprehensive approach encompassing molecular data from various biological levels is lacking. METHODS This study conducted different analyses, including the identification of differentially expressed genes (DEGs), weighted correlation networks (WGCNA), single-cell RNA sequencing (scRNA-seq), mRNA expression-based stemness index (mRNAsi), and multiCox analysis, utilizing data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, the machine learning algorithms including least absolute shrinkage and selection operator (LASSO) regression and random forest (RF), combined with multiCox analysis were exploited to identify hub genes. These findings were then validated through the receiver operating characteristic (ROC) curve and Kaplan-Meier analysis, and were experimentally confirmed in GC samples by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS Integrated analysis of TCGA and GEO databases, coupled with LASSO regression and RF algorithms, allowed us to identify 18 hub genes encoding differentially expressed secreted proteins in GC. The results of RT-PCR and bioinformatics analysis revealed four promising biomarkers with optimal diagnostic and prognostic potential. ROC analysis and Kaplan-Meier curves highlighted CHI3L1, FCGBP, VSIG2, and TFF2 as promising biomarkers for GC, offering superior modeling accuracy. These findings were further confirmed by RT-PCR and ELISA, affirming the clinical utility of these four biomarkers. Additionally, CIBERSORT analysis indicated a potential correlation between the four biomarkers and the infiltration of B memory cells and Treg cells. CONCLUSION This study unveiled four promising biomarkers present in the serum of patients with GC, which could serve as powerful indicators of GC and provide valuable insights for further research into GC pathogenesis.
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Affiliation(s)
- Yi Liu
- Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Artificial Intelligence Medicine, Shanghai Academy of Experimental Medicine, Shanghai, China
| | - Bingxian Bian
- Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shiyu Chen
- Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bingqian Zhou
- Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peng Zhang
- Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lisong Shen
- Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Artificial Intelligence Medicine, Shanghai Academy of Experimental Medicine, Shanghai, China
- Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Chen
- Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Artificial Intelligence Medicine, Shanghai Academy of Experimental Medicine, Shanghai, China
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Song Y, Liu S, Liu X, Jia H, Shi H, Liu X, Hao D, Wang H, Xing X. An Integrated Radiopathomics Machine Learning Model to Predict Pathological Response to Preoperative Chemotherapy in Gastric Cancer. Acad Radiol 2025; 32:134-145. [PMID: 39214816 DOI: 10.1016/j.acra.2024.08.014] [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: 05/21/2024] [Revised: 08/06/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
RATIONALE AND OBJECTIVES Accurately predicting the pathological response to chemotherapy before treatment is important for selecting the appropriate treatment groups, formulating individualized treatment plans, and improving the survival rates of patients with gastric cancer (GC). METHODS We retrospectively enrolled 151 patients diagnosed with GC who underwent preoperative chemotherapy and surgical resection at the Affiliated Hospital of Qingdao University between January 2015 and June 2023. Both pretreatment-enhanced computer technology images and whole slide images of pathological hematoxylin and eosin-stained sections were available for each patient. The image features were extracted and used to construct an ensemble radiopathomics machine learning model. In addition, a nomogram was developed by combining the imaging features and clinical characteristics. RESULTS In total, 962 radiomics and 999 pathomics signatures were extracted from 106 patients in the training cohort. A fusion radiopathomics model was constructed using 13 radiomics and 5 pathomics signatures. The fusion model showed favorable performance compared to single-omics models, with an area under the curve (AUC) of 0.789 in the validation cohort. Moreover, a combined radiopathomics nomogram (RPN) was developed based on radiopathomics features and the Borrmann type, which is a classification method for advanced GC according to tumor growth pattern and gross morphology. The RPN showed superior predictive performance in the training (AUC 0.880) and validation cohorts (AUC 0.797). The decision curve analysis showed that RPN could provide favorable clinical benefits to patients with GC. CONCLUSIONS RPN was able to predict the pathological response to preoperative chemotherapy with high accuracy, and therefore provides a novel tool for personalized treatment of GC.
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Affiliation(s)
- Yaolin Song
- Department of Pathology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Shunli Liu
- Department of Radiology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Xinyu Liu
- Department of Pathology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Huiqing Jia
- Department of Pathology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Hailei Shi
- Department of Pathology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Xianglan Liu
- Department of Pathology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Dapeng Hao
- Department of Radiology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Hexiang Wang
- Department of Radiology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China
| | - Xiaoming Xing
- Department of Pathology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, China.
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Lee CL, Saborowski A, Vogel A. Systemic approaches in biliary tract cancers: a review in the era of multidirectional precision medicine. Expert Opin Pharmacother 2024; 25:2385-2397. [PMID: 39560069 DOI: 10.1080/14656566.2024.2432488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 11/20/2024]
Abstract
INTRODUCTION Despite a rising incidence, biliary tract cancers (BTCs) are still considered a rare tumor entity. The disease's subtle clinical presentation and lack of effective early detection strategies often lead to a diagnosis at an advanced or unresectable stage, where curative options are limited. AREAS COVERED This review provides an overview of current systemic therapies and emerging novel approaches for BTC. For decades, the combination of gemcitabine with cisplatin (GemCis) has been the standard of care for palliative treatment. However, since 2020, the diagnostic and therapeutic landscape for BTC has evolved considerably, not only in the first-line setting but also beyond, driven by the development of clinical trials exploring immunotherapy and molecularly targeted agents. Due to the high frequency of targetable genetic alterations in BTC patients, there is a growing emphasis on obtaining tissue or liquid biopsy samples to identify markers like microsatellite instability and other actionable oncogenic driver genes. EXPERT OPINION Early initiation of systemic therapies in combination with multimodal approaches is essential for maximizing survival outcomes in patients with BTC.
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Affiliation(s)
- Cha Len Lee
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Ontario, Canada
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Arndt Vogel
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Ontario, Canada
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada
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Lu Y, Wang H, Chen S, Yang B, Li Y, Li Y. Cystatin SA attenuates gastric cancer cells growth and increases sensitivity to oxaliplatin via PI3K/AKT signaling pathway. J Cancer Res Clin Oncol 2024; 150:244. [PMID: 38717526 PMCID: PMC11078793 DOI: 10.1007/s00432-024-05780-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 05/03/2024] [Indexed: 05/12/2024]
Abstract
PURPOSE Cystatin SA (CST2) belongs to the superfamily of cysteine protease inhibitors. Emerging research indicates that CST2 is often dysregulated across various cancers. Its role and molecular mechanisms in gastric cancer remain underexplored. This study aims to explore the expression and function of CST2 in gastric cancer. METHODS CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed. In addition, multiple assays, including cell proliferation, colony formation, wound-healing, and transwell migration/invasion, were considered to ascertain the influence of CST2 overexpression on gastric cancer. The cell cycle and apoptosis were detected by flow cytometry. RESULTS CST2 expression at the protein level was decreased to be reduced in both gastric cancer tissues and cell lines, and CST2 expression attenuate gastric cancer growth, an effect restricted to gastric cancer cells and absent in gastric epithelial GES-1 cells. Furthermore, CST2 was demonstrated to improve chemosensitivity to Oxaliplatin in gastric cancer cells through the PI3K/AKT signaling pathway. CONCLUSION These findings indicate that CST2 is downregulated at the protein level in gastric cancer tissues and cell lines. Additionally, CST2 was found to attenuate the growth of gastric cancer cells and to enhance sensitivity to Oxaliplatin through the PI3K/AKT signaling pathway, specific to gastric cancer cell lines. CST2 may serve as a tumor suppressor gene increasing sensitivity to Oxaliplatin in gastric cancer.
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Affiliation(s)
- Yida Lu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China
| | - Huizhen Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China
| | - Sihan Chen
- Taikang Ningbo Hospital, Ningbo, Zhejiang, 315000, People's Republic of China
| | - Bo Yang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China
| | - Yaxian Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China
| | - Yongxiang Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.
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Zeng J, Song D, Li K, Cao F, Zheng Y. Deep learning model for predicting postoperative survival of patients with gastric cancer. Front Oncol 2024; 14:1329983. [PMID: 38628668 PMCID: PMC11018873 DOI: 10.3389/fonc.2024.1329983] [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: 11/02/2023] [Accepted: 03/18/2024] [Indexed: 04/19/2024] Open
Abstract
Background Prognostic prediction for surgical treatment of gastric cancer remains valuable in clinical practice. This study aimed to develop survival models for postoperative gastric cancer patients. Methods Eleven thousand seventy-five patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and 122 patients from the Chinese database were used for external validation. The training cohort was created to create three separate models, including Cox regression, RSF, and DeepSurv, using data from the SEER database split into training and test cohorts with a 7:3 ratio. Test cohort was used to evaluate model performance using c-index, Brier scores, calibration, and the area under the curve (AUC). The new risk stratification based on the best model will be compared with the AJCC stage on the test and Chinese cohorts using decision curve analysis (DCA), the net reclassification index (NRI), and integrated discrimination improvement (IDI). Results It was discovered that the DeepSurv model predicted postoperative gastric cancer patients' overall survival (OS) with a c-index of 0.787; the area under the curve reached 0.781, 0.798, 0.868 at 1-, 3- and 5- years, respectively; the Brier score was below 0.25 at different time points; showing an advantage over the Cox and RSF models. The results are also validated in the China cohort. The calibration plots demonstrated good agreement between the DeepSurv model's forecast and actual results. The NRI values (test cohort: 0.399, 0.288, 0.267 for 1-, 3- and 5-year OS prediction; China cohort:0.399, 0.288 for 1- and 3-year OS prediction) and IDI (test cohort: 0.188, 0.169, 0.157 for 1-, 3- and 5-year OS prediction; China cohort: 0.189, 0.169 for 1- and 3-year OS prediction) indicated that the risk score stratification performed significantly better than the AJCC staging alone (P < 0.05). DCA showed that the risk score stratification was clinically useful and had better discriminative ability than the AJCC staging. Finally, an interactive native web-based prediction tool was constructed for the survival prediction of patients with postoperative gastric cancer. Conclusion In this study, a high-performance prediction model for the postoperative prognosis of gastric cancer was developed using DeepSurv, which offers essential benefits for risk stratification and prognosis prediction for each patient.
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Affiliation(s)
| | | | | | | | - Yongbin Zheng
- Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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9
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Adili D, Mohetaer A, Zhang W. Diagnostic accuracy of radiomics-based machine learning for neoadjuvant chemotherapy response and survival prediction in gastric cancer patients: A systematic review and meta-analysis. Eur J Radiol 2024; 173:111249. [PMID: 38382422 DOI: 10.1016/j.ejrad.2023.111249] [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: 07/24/2023] [Revised: 11/07/2023] [Accepted: 11/30/2023] [Indexed: 02/23/2024]
Abstract
BACKGROUND In recent years, researchers have explored the use of radiomics to predict neoadjuvant chemotherapy outcomes in gastric cancer (GC). Yet, a lingering debate persists regarding the accuracy of these predictions. Against this backdrop, this study was conducted to examine the accuracy of radiomics in predicting the response to neoadjuvant chemotherapy in GC patients. METHODS An exhaustive search of relevant studies was conducted in PubMed, Cochrane, Embase, and Web of Science databases up to February 21, 2023. The radiomics quality scoring (RQS) tool was employed to assess study quality. Tumor response to neoadjuvant chemotherapy and survival outcomes were examined as outcome measures. RESULTS Fourteen studies involving 3,373 GC patients who had received neoadjuvant chemotherapy were incorporated in our meta-analysis. The mean RQS score across all studies was 36.3%, ranging between 0 and 63.9%. On the validation cohort, when the modeling variables were restricted to radiomic features alone, the predictive performance was characterized by a c-index of 0.750 (95% CI: 0.710-0.790), with a sensitivity of 0.67 (95% CI: 0.58-0.75) and a specificity of 0.77 (95% CI: 0.69-0.84) for the prediction of neoadjuvant chemotherapy response. When clinical data was integrated with radiomic features as modeling variables, the predictive performance improved, yielding a c-index of 0.814 (95% CI: 0.780-0.847), a sensitivity of 0.78 [95% CI: 0.70-0.84], and a specificity of 0.73 [95% CI: 0.67-0.79]. CONCLUSIONS Radiomics holds promise to noninvasively predict neoadjuvant chemotherapy response and survival outcomes among patients with locally advanced GC. Additionally, we underscore the need for future multicenter studies and the development of imaging-sourced tools for risk stratification in this patient population.
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Affiliation(s)
- Diliyaer Adili
- Department of Gastrointestinal (Oncology) Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 China
| | - Aibibai Mohetaer
- Department of Cardiology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, 830063 China
| | - Wenbin Zhang
- Department of Gastrointestinal (Oncology) Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 China
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10
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Mithany RH, Shahid MH, Manasseh M, Saeed MT, Aslam S, Mohamed MS, Daniel N. Gastric Cancer: A Comprehensive Literature Review. Cureus 2024; 16:e55902. [PMID: 38595903 PMCID: PMC11003650 DOI: 10.7759/cureus.55902] [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] [Accepted: 03/10/2024] [Indexed: 04/11/2024] Open
Abstract
Gastric cancer stands as a significant global health concern, particularly prevalent in Eastern Asia, with high mortality rates urging urgent attention and research efforts. This article comprehensively explores the epidemiology, anatomy, risk factors, pathophysiology, clinical presentation, diagnosis, staging, treatment modalities, prevention strategies, and survival rates associated with gastric cancer. Notably, Helicobacter pylori infection, dietary choices, and intricate stomach anatomy play pivotal roles in disease development. Early detection, utilizing staging, grading, and genetic testing for personalized treatment approaches is emphasized. Treatment modalities encompass surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Prevention strategies involve lifestyle changes, screening, and genetic counseling. Survival rates vary by stage, highlighting the need for individualized care. In conclusion, a collaborative global effort is essential to address the impact of gastric cancer and improve outcomes.
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Affiliation(s)
- Reda H Mithany
- Laparoscopic Colorectal Surgery, Kingston Hospital NHS Foundation Trust, Kingston Upon Thames, GBR
| | | | - Mina Manasseh
- General Surgery, Torbay and South Devon NHS Foundation Trust, Torquay, GBR
| | | | - Samana Aslam
- General Surgery, Lahore General Hospital, Lahore, PAK
| | | | - Nesma Daniel
- Medical Laboratory Science, Ain Shams University Specialized Hospital, Cairo, EGY
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11
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Liu X, Ou J. The development of prognostic gene markers associated with disulfidptosis in gastric cancer and their application in predicting drug response. Heliyon 2024; 10:e26013. [PMID: 38384541 PMCID: PMC10878937 DOI: 10.1016/j.heliyon.2024.e26013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/24/2023] [Accepted: 02/06/2024] [Indexed: 02/23/2024] Open
Abstract
Background Gastric cancer (GC) is a malignancy known for its high fatality rate. Disulfidptosis, a potentially innovative therapeutic strategy for cancer treatment, has been proposed. Nevertheless, the specific involvement of disulfidptosis in the context of GC remains uncertain. Methods The mRNA expression profiles were obtained from the TCGA and GEO databases. Univariate and LASSO Cox regression analyses were employed to identify differentially expressed genes and develop a risk model for disulfidptosis-related genes. The performance of the model was evaluated using Kaplan-Meier curve, ROC curve, and nomogram. Univariate and multivariate Cox regression analyses were conducted to determine if the risk model could serve as an independent prognostic factor. The biological function of the identified genes was assessed through GO, KEGG, and GSEA analyses. The prediction of drug response was conducted employing the package "pRRophetic". Furthermore, gene expression was determined using qRT-PCR. Results An eight-gene signature were identified and utilized to categorize patients into low- and high-risk groups. Survival, receiver operating characteristic (ROC) curve, and Cox analyses provided clarification that these eight hub genes served as a favorable independent prognostic factor for patients with GC. A nomogram was constructed by integrating clinical parameters with the risk signatures, demonstrating high precision in predicting 1-, 3-, and 5-year survival rates. Additionally, drug sensitivity was different in the high-risk and low-risk groups, and the expression of three genes was verified by qRT-PCR. Conclusion The prognostic risk model developed in this study demonstrates the potential to accurately forecast the prognosis of patients with GC.
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Affiliation(s)
- Xing Liu
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Jianghong Ou
- Department of Integrated Chinese and Western Medicine, Changsha Central Hospital, Nanhua University, Changsha, 410000, China
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12
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Zhong W, Lin J, Wu C, Wang J, Chen J, Zheng H, Ye K. Efficacy and safety of camrelizumab combined with oxaliplatin and S-1 as neoadjuvant treatment in locally advanced gastric or gastroesophageal junction cancer: A phase II, single-arm study. Cancer Med 2024; 13:e7006. [PMID: 38400680 PMCID: PMC10891470 DOI: 10.1002/cam4.7006] [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: 07/25/2023] [Revised: 11/02/2023] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
PURPOSE In the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S-1 in patients with resectable gastric or gastroesophageal junction cancer. METHODS In this single-arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S-1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event-free survival (EFS), overall survival (OS), and safety. RESULTS Between September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2-27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment-emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune-related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred. CONCLUSION The neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S-1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer.
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Affiliation(s)
- Wen‐Jin Zhong
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Jian‐An Lin
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Chu‐Ying Wu
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Jiantian Wang
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Jun‐Xing Chen
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Huida Zheng
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Kai Ye
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
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13
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Li B, Geng X. The impact of neoadjuvant chemotherapy on the clinical efficacy and serum tumor marker levels in patients undergoing radical surgery for gastric cancer. Medicine (Baltimore) 2024; 103:e36040. [PMID: 38215107 PMCID: PMC10783286 DOI: 10.1097/md.0000000000036040] [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: 07/23/2023] [Accepted: 10/19/2023] [Indexed: 01/14/2024] Open
Abstract
The objective of this article is to study the impact of neoadjuvant chemotherapy (NAC) on the clinical efficacy and serum tumor marker levels in patients undergoing radical surgery for gastric cancer (GC). Thirty patients who underwent routine radical surgery for GC in our hospital from January 2020 to June 2021 were included in the control group. Thirty patients who underwent radical surgery for GC after receiving NAC from July 2021 to December 2022 were included in the observation group. The treatment outcomes of the observation group were assessed and analyzed. The surgical indicators, tumor markers, Karnofsky Performance Status (KPS), and occurrence of adverse reactions were compared between the 2 groups. Comparisons were made between the 2 groups in terms of surgical duration, number of lymph node dissections, intraoperative blood loss, time to postoperative ambulation, length of hospital stay, and time to postoperative passage of flatus (P > .05). The observation group had a higher proportion of R0 resection at the surgical margin compared to the control group (P < .05). The serum tumor markers of the 2 groups were compared before treatment (P > .05). After treatment, the levels of serum carcinoembryonic antigen, alpha-fetoprotein, cancer antigen 125, and carbohydrate antigen 72-4 decreased in both groups, and the observation group showed a greater reduction in these tumor marker levels compared to the control group (P < .05). The KPS scores of the 2 groups were compared before treatment (P > .05). After treatment, the KPS scores increased in both groups, with the observation group showing a higher improvement compared to the control group (P < .05). The overall incidence of adverse reactions, including incision infection, pleural effusion, pulmonary infection, intestinal obstruction, and gastric emptying disorders, was lower in the observation group (6.67%) compared to the control group (26.67%) (P < .05). The combination of NAC with radical surgery for GC is safe and feasible. It can significantly increase the R0 resection rate, effectively improve the levels of serum tumor markers, enhance patient's quality of life, and result in fewer surgical adverse reactions.
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Affiliation(s)
- Bingqiang Li
- Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu Province, China
| | - Xuan Geng
- Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu Province, China
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14
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Jeong SA, Kim S, Lee IS, Yoo MW, Kim BS. Does total omentectomy prevent peritoneal seeding for advanced gastric cancer with serosal invasion? Surg Endosc 2024; 38:97-104. [PMID: 37917161 DOI: 10.1007/s00464-023-10514-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: 04/25/2023] [Accepted: 10/08/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND Radical gastrectomy is composed of gastrectomy, lymph node dissection, and omentectomy. Total omentectomy (TO) is expected to reduce the incidence of peritoneal recurrence. We aimed to investigate the necessity of TO for advanced gastric cancer (AGC) with serosal invasion. METHODS We retrospectively reviewed 310 patients who underwent radical gastrectomy with TO and 93 patients who underwent partial omentectomy (PO) for gastric cancer with serosal invasion between August, 2005 and December, 2017. Finally, 91 patients in the PO group and 91 in the TO group were enrolled based on a 1:1 propensity-score matching analysis. We evaluated surgical and oncological outcomes, including 5-year overall and recurrence-free survival rates. RESULTS There was no statistically significant difference between the two groups in postoperative complications. Recurrence sites showed similar patterns in both groups, including peritoneal recurrence (PO vs. TO, 18.7% vs. 28.6%; p = 0.188). Five-year overall survival was better in the PO group (p = 0.018), while 5-year recurrence-free survival was similar in both groups (p = 0.066). CONCLUSION TO might not be an essential part of preventing peritoneal recurrence for AGC with serosal invasion. PO could be considered a radical gastrectomy for T4a gastric cancer.
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Affiliation(s)
- Seong-A Jeong
- Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, 25440, Korea
| | - Sehee Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - In-Seob Lee
- Department of Gastrointestinal Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Moon-Won Yoo
- Department of Gastrointestinal Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Beom Su Kim
- Department of Gastrointestinal Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
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15
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Li J, Ma C. Anxiety and depression during 3-year follow-up period in postoperative gastrointestinal cancer patients: prevalence, vertical change, risk factors, and prognostic value. Ir J Med Sci 2023; 192:2621-2629. [PMID: 36862310 DOI: 10.1007/s11845-023-03318-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 02/13/2023] [Indexed: 03/03/2023]
Abstract
BACKGROUND Anxiety and depression are common issues in gastrointestinal cancer, bringing negative impacts on patients' quality of life and long-term prognosis. This study aimed to identify the prevalence, longitudinal variation, risk factors, and prognostic value of anxiety and depression in postoperative gastrointestinal cancer patients. METHODS A total of 320 gastrointestinal cancer patients after surgical resection (210 colorectal cancer (CRC) patients and 110 gastric cancer (GC) patients) were enrolled in this study. During the 3-year follow-up period, Hospital Anxiety and Depression Scale (HADS)-anxiety (HADS-A) and HADS-depression (HADS-D) scores were determined at baseline, 12th month (M12), 24th month (M24), and 36th month (M36). RESULTS The prevalence of anxiety and depression at baseline was 39.7% and 33.4% in postoperative gastrointestinal cancer patients, respectively. Female (vs. male), single/divorced/widowed (vs. married), CRC (vs. GC), hypertension, higher TNM stage, neoadjuvant chemotherapy, and postoperative complications were independent risk factors of anxiety or depression in patients with gastrointestinal cancer (all P < 0.050). Furthermore, anxiety (P = 0.014) and depression (P < 0.001) were associated with shortened overall survival (OS); after further adjustment, depression was independently linked with shortened OS (P < 0.001), while anxiety was not. During the follow-up period, HADS-A score (from 7.78 ± 3.180 to 8.57 ± 2.854, P < 0.001), HADS-D score (from 7.23 ± 2.711 to 8.01 ± 2.786, P < 0.001), anxiety rate (from 39.7 to 49.2%, P = 0.019), and depression rate (from 33.4 to 42.6%, P = 0.023) were all gradually increased from baseline to M36. CONCLUSION Anxiety and depression gradually exacerbate and relate to poor survival in postoperative gastrointestinal cancer patients.
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Affiliation(s)
- Jiaying Li
- Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China
| | - Chongyi Ma
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, Heilongjiang, 150086, China.
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Stüben BO, Plitzko GA, Stern L, Li J, Neuhaus JP, Treckmann JW, Schmeding R, Saner FH, Hoyer DP. Prognostic factors of poor postoperative outcomes in gastrectomies. Front Surg 2023; 10:1324247. [PMID: 38107405 PMCID: PMC10722220 DOI: 10.3389/fsurg.2023.1324247] [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: 10/19/2023] [Accepted: 11/21/2023] [Indexed: 12/19/2023] Open
Abstract
Background Gastric cancer is one of the most common cancers worldwide and is the third most common cause of cancer related death. Improving postoperative results by understanding risk factors which impact outcomes is important. The current study aimed to compare immediate perioperative outcomes following gastrectomy. Methods 302 patients following gastric resections over a 10-year period (January 2009-January 2020) were identified in a database and retrospectively analysed. Epidemiological as well as perioperative data was analysed, and a univariate and multivariate analysis performed to identify risk factors for in-hospital mortality. Results In general, gastrectomies were mainly performed electively (total vs. subtotal 95% vs. 85%, p = 0.004). Patients having subtotal gastrectomy needed significantly more PRBC transfusions compared to total gastrectomy (p = 0.039). Most emergency surgeries were performed for benign diseases, such as ulcer perforations or bleeding and gastric ischaemia. Only emergency surgery was significantly associated with poorer overall survival (HR 2.68, 95% CI 1.32-5.05, p = 0.003). Conclusion In-hospital mortality was comparable between total and subtotal gastrectomies. Only emergency interventions increased postoperative fatality risk.
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Affiliation(s)
- B. O. Stüben
- Department of General, Visceral and Transplant Surgery, Medical Centre University Duisburg-Essen, Essen, Germany
| | - G. A. Plitzko
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - L. Stern
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - J. Li
- Department of Surgery, Jiahui International Hospital, Shanghai, China
| | - J. P. Neuhaus
- Department of General, Visceral and Transplant Surgery, Medical Centre University Duisburg-Essen, Essen, Germany
| | - J. W. Treckmann
- Department of General, Visceral and Transplant Surgery, Medical Centre University Duisburg-Essen, Essen, Germany
| | - R. Schmeding
- Department of General, Visceral and Transplant Surgery, Medical Centre University Duisburg-Essen, Essen, Germany
| | - F. H. Saner
- Department of General, Visceral and Transplant Surgery, Medical Centre University Duisburg-Essen, Essen, Germany
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - D. P. Hoyer
- Department of General, Visceral and Transplant Surgery, Medical Centre University Duisburg-Essen, Essen, Germany
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Chen H, Hu Y, Zhuang Z, Wang D, Ye Z, Jing J, Cheng X. Advancements and Obstacles of PARP Inhibitors in Gastric Cancer. Cancers (Basel) 2023; 15:5114. [PMID: 37958290 PMCID: PMC10647262 DOI: 10.3390/cancers15215114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 11/15/2023] Open
Abstract
Gastric cancer (GC) is a common and aggressive cancer of the digestive system, exhibiting high aggressiveness and significant heterogeneity. Despite advancements in improving survival rates over the past few decades, GC continues to carry a worrisome prognosis and notable mortality. As a result, there is an urgent need for novel therapeutic approaches to address GC. Recent targeted sequencing studies have revealed frequent mutations in DNA damage repair (DDR) pathway genes in many GC patients. These mutations lead to an increased reliance on poly (adenosine diphosphate-ribose) polymerase (PARP) for DNA repair, making PARP inhibitors (PARPi) a promising treatment option for GC. This article presents a comprehensive overview of the rationale and development of PARPi, highlighting its progress and challenges in both preclinical and clinical research for treating GC.
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Affiliation(s)
- Hongjie Chen
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; (H.C.); (Y.H.); (D.W.)
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Yangchan Hu
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; (H.C.); (Y.H.); (D.W.)
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Zirui Zhuang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences (UCAS), Hangzhou 310024, China
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Dingyi Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; (H.C.); (Y.H.); (D.W.)
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Zu Ye
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Hangzhou 310022, China
| | - Ji Jing
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Hangzhou 310022, China
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Hangzhou 310022, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, China
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Collatuzzo G, Pelucchi C, Negri E, Kogevinas M, Huerta JM, Vioque J, de la Hera MG, Tsugane S, Shigueaki Hamada G, Hidaka A, Zhang ZF, Camargo MC, Curado MP, Lunet N, La Vecchia C, Boffetta P. Sleep Duration and Stress Level in the Risk of Gastric Cancer: A Pooled Analysis of Case-Control Studies in the Stomach Cancer Pooling (StoP) Project. Cancers (Basel) 2023; 15:4319. [PMID: 37686594 PMCID: PMC10486543 DOI: 10.3390/cancers15174319] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 08/17/2023] [Accepted: 08/24/2023] [Indexed: 09/10/2023] Open
Abstract
The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23-2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22-2.08, and cardia OR = 1.63, 95% CI = 0.97-2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14-2.40 and intestinal OR = 1.24, 95% CI = 0.91-1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18-1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12-1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11-1.58) and intestinal type (OR = 1.23, 95% CI = 1.07-1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and <0.001, respectively). In conclusion, long sleep duration (≥9 h) was associated with GC and its subtype categories. Stress linearly increased the risk of GC and was related to noncardia GC.
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Affiliation(s)
- Giulia Collatuzzo
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy (E.N.)
| | - Claudio Pelucchi
- Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology “G.A. Maccacaro”, University of Milan, 20133 Milan, Italy; (C.P.); (C.L.V.)
| | - Eva Negri
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy (E.N.)
- Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology “G.A. Maccacaro”, University of Milan, 20133 Milan, Italy; (C.P.); (C.L.V.)
| | - Manolis Kogevinas
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (M.K.); (J.V.); (M.G.d.l.H.)
- Barcelona Institute for Global Health—ISGlobal, 08036 Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
- Department de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
| | - José María Huerta
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (M.K.); (J.V.); (M.G.d.l.H.)
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, 30120 Murcia, Spain
| | - Jesus Vioque
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (M.K.); (J.V.); (M.G.d.l.H.)
- Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernandez (ISABIAL-UMH), 03010 Alicante, Spain
| | - Manoli García de la Hera
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (M.K.); (J.V.); (M.G.d.l.H.)
- Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernandez (ISABIAL-UMH), 03010 Alicante, Spain
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo 104-0045, Japan
- National Institute of Biomedical Innovation, Health and Nutrition, Tokyo 566-0002, Japan
| | | | - Akihisa Hidaka
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo 104-0045, Japan
| | - Zuo-Feng Zhang
- Department of Epidemiology, UCLA Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA;
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA
| | - Maria Paula Curado
- Centro Internacional de Pesquisas, A.C.Camargo Cancer Center, São Paulo 01509-010, Brazil
| | - Nuno Lunet
- EPIUnit—Instituto de Saúde Pública da Universidade do Porto, 4050-091 Porto, Portugal;
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), 4050-600 Porto, Portugal
- Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina da Universidade do Porto, 4200-450 Porto, Portugal
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology “G.A. Maccacaro”, University of Milan, 20133 Milan, Italy; (C.P.); (C.L.V.)
| | - Paolo Boffetta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy (E.N.)
- Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA
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19
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Jiang C, Zhang J, Wang W, Shan Z, Sun F, Tan Y, Tong Y, Qiu Y. Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets. Front Physiol 2023; 14:1158839. [PMID: 37664422 PMCID: PMC10469264 DOI: 10.3389/fphys.2023.1158839] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease.
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Affiliation(s)
- Chengyao Jiang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Jianjun Zhang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Wentao Wang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Zexing Shan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Fan Sun
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yuen Tan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yilin Tong
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yue Qiu
- Medical Oncology Department of Gastrointestinal Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
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20
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Pang HY, Chen XF, Chen LH, Yan MH, Chen ZX, Sun H. Comparisons of perioperative and long-term outcomes of laparoscopic versus open gastrectomy for advanced gastric cancer after neoadjuvant therapy: an updated pooled analysis of eighteen studies. Eur J Med Res 2023; 28:224. [PMID: 37408041 DOI: 10.1186/s40001-023-01197-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Accepted: 06/25/2023] [Indexed: 07/07/2023] Open
Abstract
BACKGROUND Outcomes of laparoscopic surgery in advanced gastric cancer patients who received neoadjuvant therapy represent a controversial issue. We performed an updated meta-analysis to evaluate the perioperative and long-term survival outcomes of laparoscopic gastrectomy (LG) versus conventional open gastrectomy (OG) in this subset of patients. METHODS Electronic databases including PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure were comprehensively searched up to May 2023. The short-term and long-term outcomes of LG versus OG in advanced gastric cancer patients undergoing neoadjuvant therapy were evaluated. Effect sizes with 95% confidence intervals were always assessed using random-effects model. The prospective protocol was registered with PROSPERO (CRD42022359126). RESULTS Eighteen studies (2 randomized controlled trials and 16 cohort studies) involving 2096 patients were included. In total, 933 patients were treated with LG and 1163 patients were treated with OG. In perioperative outcomes, LG was associated with less estimated blood loss (MD = - 65.15; P < 0.0001), faster time to flatus (MD = - 0.56; P < 0.0001) and liquid intake (MD = - 0.42; P = 0.02), reduced hospital stay (MD = - 2.26; P < 0.0001), lower overall complication rate (OR = 0.70; P = 0.002) and lower minor complication rate (OR = 0.69; P = 0.006), while longer operative time (MD = 25.98; P < 0.0001). There were no significant differences between the two groups in terms of proximal margin, distal margin, R1/R2 resection rate, retrieved lymph nodes, time to remove gastric tube and drainage tube, major complications and other specific complications. In survival outcomes, LG and OG were not significantly different in overall survival, disease-free survival and recurrence-free survival. CONCLUSION LG can be a safe and feasible technique for the treatment of advanced gastric cancer patients receiving neoadjuvant therapy. However, more high-quality randomized controlled trials are still needed to further validate the results of our study.
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Affiliation(s)
- Hua-Yang Pang
- Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Xiu-Feng Chen
- Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Li-Hui Chen
- Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Meng-Hua Yan
- Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Zhi-Xiong Chen
- Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Hao Sun
- Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
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21
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Liu T, Zhou X, Zhang Z, Qin Y, Wang R, Qin Y, Huang Y, Mo Y, Huang T. The role of EBV-encoded miRNA in EBV-associated gastric cancer. Front Oncol 2023; 13:1204030. [PMID: 37388232 PMCID: PMC10301731 DOI: 10.3389/fonc.2023.1204030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 05/31/2023] [Indexed: 07/01/2023] Open
Abstract
Epstein-Barr virus (human herpesvirus 4, EBV) is a linear double-stranded DNA virus that infects over 90% of the population worldwide. However, our understanding of EBV's contribution to tumorigenesis of EBV-associated GC (EBVaGC) remains incomplete. Recent advancements in EBVaGC research have highlighted that EBV-encoded microRNAs (miRNAs) play prominent roles in critical cellular processes such as migration, cell cycle, apoptosis, cell proliferation, immune response, and autophagy. Notably, the largest group of EBV-encoded miRNAs, known as BamHI-A rightward transcripts (BARTs), exhibit bidirectional effects in EBVaGC. For instance, they present both anti-apoptotic and pro-apoptotic functions and enhance chemosensitivity while also conferring resistance to 5-fluorouracil. Despite these findings, the comprehensive mechanisms through which miRNAs contribute to EBVaGC are yet to be fully elucidated. In this work, we summarize the current evidence of the roles of miRNA in EBVaGC, particularly with the application of multi-omic techniques. Additionally, we discuss the application of miRNA in EBVaGC in retrospective analyses and provide novel perspectives on the use of miRNA in EBVaGC in translational medicine.
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Affiliation(s)
- Ting Liu
- Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiaoying Zhou
- Guangxi Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Ministry of Education, Guangxi Medical University, Nanning, China
| | - Zhe Zhang
- Guangxi Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Ministry of Education, Guangxi Medical University, Nanning, China
- Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yutao Qin
- Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Rensheng Wang
- Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Ministry of Education, Guangxi Medical University, Nanning, China
| | - Yanning Qin
- School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Yuqi Huang
- School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Yingxi Mo
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Tingting Huang
- Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Ministry of Education, Guangxi Medical University, Nanning, China
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22
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Development and Experimental Validation of a Novel Prognostic Signature for Gastric Cancer. Cancers (Basel) 2023; 15:cancers15051610. [PMID: 36900401 PMCID: PMC10000504 DOI: 10.3390/cancers15051610] [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: 11/11/2022] [Revised: 01/18/2023] [Accepted: 02/16/2023] [Indexed: 03/08/2023] Open
Abstract
BACKGROUND Gastric cancer is a malignant tumor with high morbidity and mortality. Therefore, the accurate recognition of prognostic molecular markers is the key to improving treatment efficacy and prognosis. METHODS In this study, we developed a stable and robust signature through a series of processes using machine-learning approaches. This PRGS was further experimentally validated in clinical samples and a gastric cancer cell line. RESULTS The PRGS is an independent risk factor for overall survival that performs reliably and has a robust utility. Notably, PRGS proteins promote cancer cell proliferation by regulating the cell cycle. Besides, the high-risk group displayed a lower tumor purity, higher immune cell infiltration, and lower oncogenic mutation than the low-PRGS group. CONCLUSIONS This PRGS could be a powerful and robust tool to improve clinical outcomes for individual gastric cancer patients.
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23
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Sato Y, Okamoto K, Kida Y, Mitsui Y, Kawano Y, Sogabe M, Miyamoto H, Takayama T. Overview of Chemotherapy for Gastric Cancer. J Clin Med 2023; 12:jcm12041336. [PMID: 36835872 PMCID: PMC9959005 DOI: 10.3390/jcm12041336] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 01/22/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Gastric cancer (GC) is one of the most clinically challenging cancers worldwide. Over the past few years, new molecular-targeted agents and immunotherapy have markedly improved GC prognosis. Human epidermal growth factor receptor 2 (HER2) expression is a key biomarker in first-line chemotherapy for unresectable advanced GC. Further, the addition of trastuzumab to cytotoxic chemotherapy has extended the overall survival of patients with HER2-positive advanced GC. In HER2-negative GC, the combination of nivolumab, an immune checkpoint inhibitor, and a cytotoxic agent has been demonstrated to prolong the overall survival of GC patients. Ramucirumab and trifluridine/tipiracil, which are second- and third-line treatments for GC, and trastuzumab deruxtecan, an antibody-drug conjugate for HER2-positive GC, have been introduced in clinics. New promising molecular-targeted agents are also being developed, and combination therapy comprising immunotherapy and molecular-targeted agents is expected. As the number of available drugs increases, it is important to understand the target biomarkers and drug characteristics and select the optimal therapy for each patient. For resectable disease, differences in the extent of standard lymphadenectomy between Eastern and Western countries have led to different standard treatments: perioperative (neoadjuvant) and adjuvant therapy. This review aimed to summarize recent advances in chemotherapy for advanced GC.
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Affiliation(s)
- Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
- Correspondence: ; Tel.: +81-88-633-7124
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Yoshifumi Kida
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Yasuhiro Mitsui
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Yutaka Kawano
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Masahiro Sogabe
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
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24
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Beyer K. Surgery Matters: Progress in Surgical Management of Gastric Cancer. Curr Treat Options Oncol 2023; 24:108-129. [PMID: 36656504 PMCID: PMC9883345 DOI: 10.1007/s11864-022-01042-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2022] [Indexed: 01/20/2023]
Abstract
OPINION STATEMENT The surgical treatment of gastric carcinoma has progressed significantly in the past few decades. A major milestone was the establishment of multimodal therapies for locally advanced tumours. Improvements in the technique of endoscopic resection have supplanted surgery in the early stages of many cases of gastric cancer. In cases in which an endoscopic resection is not possible, surgical limited resection procedures for the early stages of carcinoma are an equal alternative to gastrectomy in the field of oncology. Proximal gastrectomy is extensively discussed in this context. Whether proximal gastrectomy leads to a better quality of life and better nutritional well-being than total gastrectomy depends on the reconstruction chosen. The outcome cannot be conclusively assessed at present. For locally advanced stages, total or subtotal gastrectomy with D2 lymphadenectomy is now the global standard. A subtotal gastrectomy requires sufficiently long tumour-free proximal resection margins. Recent data indicate that proximal margins of at least 3 cm for tumours with an expansive growth pattern and at least 5 cm for those with an infiltrative growth pattern are sufficient. The most frequently performed reconstruction worldwide following gastrectomy is the Roux-en-Y reconstruction. However, there is evidence that pouch reconstruction is superior in terms of quality of life and nutritional well-being. Oncological gastric surgery is increasingly being performed laparoscopically. The safety and oncological equivalency were first demonstrated for early carcinomas and then for locally advanced tumours, by cohort studies and RCTs. Some studies suggest that laparoscopic procedures may be advantageous in early postoperative recovery. Robotic gastrectomy is also increasing in use. Preliminary results suggest that robotic gastrectomy may have added value in lymphadenectomy and in the early postoperative course. However, further studies are needed to substantiate these results. There is an ongoing debate about the best treatment option for gastric cancer with oligometastatic disease. Preliminary results indicate that certain patient groups could benefit from resection of the primary tumour and metastases following chemotherapy. However, the exact conditions in which patients may benefit have yet to be confirmed by ongoing trials.
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Affiliation(s)
- Katharina Beyer
- Department of General and Visceral Surgery, Charité University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
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25
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Usman M, Beilerli A, Sufianov A, Kudryashov V, Ilyasova T, Balaev P, Danilov A, Lu H, Gareev I. Investigations into the impact of non-coding RNA on the sensitivity of gastric cancer to radiotherapy. Front Physiol 2023; 14:1149821. [PMID: 36909247 PMCID: PMC9998927 DOI: 10.3389/fphys.2023.1149821] [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: 01/23/2023] [Accepted: 02/16/2023] [Indexed: 02/26/2023] Open
Abstract
Non-coding RNAs (ncRNAs) are a newly discovered functional RNA different from messenger RNA, which can participate in regulating the occurrence and development of tumors. More and more research results show that ncRNAs can participate in the regulation of gastric cancer (GC) radiotherapy response, and its mechanism may be related to its effect on DNA damage repair, gastric cancer cell stemness, cell apoptosis, activation of epidermal growth factor receptor signaling pathway, etc. This article summarizes the relevant mechanisms of ncRNAs regulating the response to radiotherapy in gastric cancer, which will be directly important for the introduction of ncRNAs particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) into clinical medicine as biomarkers and therapeutic targets.
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Affiliation(s)
- Muhammad Usman
- Department of Medical Imaging, Central Hospital Affiliated to Chongqing University of Technology, Chongqing, China
| | - Aferin Beilerli
- Department of Obstetrics and Gynecology, Tyumen State Medical University, Tyumen, Russia
| | - Albert Sufianov
- Department of Neurosurgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.,Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Valentin Kudryashov
- Gastric Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Tatiana Ilyasova
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Pavel Balaev
- Department of Oncology and Radiology, Ural State Medical University, Yekaterinburg, Russia
| | - Andrei Danilov
- Department of Clinical Pharmacology, Smolensk State Medical University, Smolensk, Russia
| | - Hong Lu
- Department of Medical Imaging, Central Hospital Affiliated to Chongqing University of Technology, Chongqing, China
| | - Ilgiz Gareev
- Educational and Scientific Institute of Neurosurgery, Рeoples' Friendship University of Russia (RUDN University), Moscow, Russia
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26
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Gastrectomy with or without Complete Omentectomy for Advanced Gastric Cancer: A Meta-Analysis. Medicina (B Aires) 2022; 58:medicina58091241. [PMID: 36143918 PMCID: PMC9503724 DOI: 10.3390/medicina58091241] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/01/2022] [Accepted: 09/06/2022] [Indexed: 02/03/2023] Open
Abstract
Background and Objectives: Surgery remains the only possible curative treatment for advanced gastric cancer (AGC). Peritoneal metastases are estimated to occur in approximately 55–60% AGC patients. Greater omentum is the most common metastatic area in AGC. At present, omentectomy alone or bursectomy are usually carried out during gastric cancer surgery. We performed a meta-analysis in order to evaluate long-term and short-term outcomes among AGC patients, who have undergone radical gastrectomy with or without complete omentectomy (CO). Materials and Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed by use of RevMan (Computer program) Version 5.4. Results: The eight included studies covered an approximately 20 years long study period (2000–2018). Almost all included studies were retrospective ones and originated from Asian countries. Meta-analysis indicated gastrectomy without CO as significantly associated with longer 3-year (RR: 0.94, 95% CI: 0.90–0.98, p = 0.005) and 5-year overall survivals (OS) (RR: 0.93, 95% CI: 0.88–0.98, p = 0.007). Moreover, we found longer operative time (MD: 24.00, 95% CI: −0.45–48.45, p = 0.05) and higher estimated blood loss (MD: 194.76, 95% CI: 96.40–293.13, p = 0.0001) in CO group. Conclusions: Non-complete omentectomy (NCO) group had a statistically greater rate in 3-year and 5-year OSs than the CO group, while the CO group had significantly longer operative time and higher estimated blood loss than the NCO group. Further randomized, possibly multi-center trials may turn out of paramount importance in confirming our results.
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