|
1
|
Zhang P, Tao C, Xie H, Yang L, Lu Y, Xi Y, Yao S, Yuan L, Guo P, Cheng X. Identification of CD66c as a potential target in gastroesophageal junction cancer for antibody-drug conjugate development. Gastric Cancer 2025; 28:422-441. [PMID: 39918687 PMCID: PMC11993476 DOI: 10.1007/s10120-025-01584-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 12/27/2024] [Indexed: 04/13/2025]
Abstract
BACKGROUND Gastroesophageal junction (GEJ) cancer exhibits unique biological characteristics and currently lacks specific targeted therapies. Given the clinical efficacy of antibody-drug conjugates (ADCs) in solid tumor treatment, we aimed to identify a novel ADC target and suitable payload for GEJ-targeted therapy. METHODS In this study, we conducted bioinformatic analyses of multi-omics data, including transcriptomics, proteomics, and phosphoproteomics, to identify CD66c as a promising ADC target for GEJ cancer. We then engineered a CD66c-directed antibody-drug conjugate (CD66c-DXd) incorporating a GGFG linker. The preclinical efficacy of CD66c-DXd was determined in multi GEJ xenograft models. RESULTS Proteomic analyses of 103 cases of GEJ cancer revealed that CD66c expression was significantly higher in tumoral tissues compared to normal tissues. Proteomic and phosphoproteomic analyses identified deruxtecan (DXd) as a potentially potent payload for ADCs targeting GEJ cancer. Furthermore, high CD66c expression in GEJ was associated with a significantly lower proportion of plasma cells. The drug-to-antibody ratio (DAR) of CD66c-DXd was determined to be 3.6. CD66c-DXd effectively and selectively ablated multiple human GEJ cell lines (OE-19, OE33 and SK-GT-4) without affecting non-malignant cells (GES-1) in vitro. Eventually, CD66c-DXd mediated potent and durable tumor regression in vivo with excellent safety profiles. CONCLUSIONS This preclinical study provides a strong rationale for the further development of CD66c-DXd as promising therapeutic candidates to treat advanced GEJ cancer. Additionally, the study demonstrates the robustness of the multi-omics data in identifying novel potential ADC targets and payloads.
Collapse
Affiliation(s)
- Peng Zhang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, Hangzhou, 310022, Zhejiang, China
| | - Changjuan Tao
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China
| | - Hanfei Xie
- Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Postgraduate Training Base Alliance of Wenzhou Medical University, Hangzhou, 310022, Zhejiang, China
| | - Liu Yang
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, Hangzhou, 310022, Zhejiang, China
| | - Ye Lu
- Clinical and Translational Research Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
| | - Yun Xi
- Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China
| | - Shili Yao
- School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, China
| | - Li Yuan
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Peng Guo
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Clinical and Translational Research Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China.
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China.
| |
Collapse
|
|
2
|
Cheng N, Wang B, Xu J, Xue L, Ying J. Tumor stroma ratio, tumor stroma maturity, tumor-infiltrating immune cells in relation to prognosis, and neoadjuvant therapy response in esophagogastric junction adenocarcinoma. Virchows Arch 2025; 486:257-266. [PMID: 38383941 DOI: 10.1007/s00428-024-03755-2] [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: 10/31/2023] [Revised: 01/14/2024] [Accepted: 01/27/2024] [Indexed: 02/23/2024]
Abstract
Accurate predictions on prognosis and neoadjuvant therapy response are crucial for esophagogastric junction adenocarcinoma (EGJA) patients. Therefore, we aimed to investigate the predictive abilities of several indicators, including tumor stroma ratio (TSR), tumor stroma maturity (TSM), and the density and spatial distribution of tumor-infiltrating immune cells (TIICs), such as T cells, B cells, and tumor-associated macrophages (TAMs). Resection and biopsy specimens of a total of 695 patients were included, obtained from the National Cancer Center (NCC) and The Cancer Genome Atlas (TCGA) cohorts. TSR and TSM were evaluated based on histological assessment. TIICs were quantified by QuPath following immunohistochemical (IHC) staining in resection specimens, while the Klintrup-Mäkinen (KM) grade was employed for evaluating TIIC in biopsy specimens. Patients with high stromal levels or immature stroma had relatively worse prognoses. Furthermore, high CD8+T cell count in the tumor periphery, as well as low CD68+ TAM count either in the tumor center or in the tumor periphery, was an independent favorable prognostic factor. Significantly, the combination model incorporating TSM and CD163+TAMs emerged as an independent prognostic factor in both two independent cohorts (HR 3.644, 95% CI 1.341-9.900, p = 0.011 and HR 1.891, 95% CI 1.195-2.99, p = 0.006, respectively). Additionally, high stromal levels in preoperative biopsies correlated with poor neoadjuvant therapy response (p < 0.05). In conclusion, our findings suggest that TSR, TSM, CD8+T cell, CD68+TAMs, and CD163+TAMs predict the prognosis to some extent in patients with EGJA. Notably, the combined model incorporating TSM and CD163+TAM can contribute significantly to prognostic stratification. Additionally, high stromal levels evaluated in preoperative biopsy specimens correlated with poor neoadjuvant therapy response.
Collapse
Affiliation(s)
- Na Cheng
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China
| | - Bingzhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China
| | - Jiaqi Xu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China.
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China.
| |
Collapse
|
|
3
|
Su PJ, Huang YT, Liao TK, Lu WH, Wang CJ, Chao YJ, Shan YS. Comparing survival after proximal gastrectomy vs. total gastrectomy in advanced gastric cancer: A systematic review and meta‑analysis. Oncol Lett 2024; 28:427. [PMID: 39021734 PMCID: PMC11253084 DOI: 10.3892/ol.2024.14560] [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: 02/21/2024] [Accepted: 06/18/2024] [Indexed: 07/20/2024] Open
Abstract
The present systematic review and meta-analysis aimed to compare long-term survival after proximal gastrectomy (PG) and total gastrectomy (TG) for locally advanced proximal gastric cancer (GC). The PubMed, EMBASE and Cochrane CENTRAL databases were searched from their inception to May 2023. Only published two-arm prospective or retrospective studies were included. The selected studies included patients with locally advanced GC who underwent PG or TG and reported quantitative survival outcomes. The primary outcome was overall survival (OS) after gastrectomy. Three studies involving a total of 4,815 patients met the inclusion criteria. The age of the patients ranged from 57.03-64.46 years and 78.80% were male. The estimated 5-year OS probability after TG varied from 30.14 to 72.0%, and from 42.06 to 74.9% after PG. Results of the meta-analyses revealed a significant association between PG and improved OS compared with that of TG, with a pooled hazard ratio of 1.15 (95% CI, 1.05-1.25). No heterogeneity was observed in the included studies (I2=0%). Overall, in managing locally advanced GC, PG demonstrated comparable or marginally improved OS compared with TG during postoperative follow-up; however, further meta-analyses are required to provide stronger evidence.
Collapse
Affiliation(s)
- Ping-Jui Su
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
| | - Yen-Ta Huang
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
| | - Ting-Kai Liao
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
| | - Wei-Hsun Lu
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
| | - Chih-Jung Wang
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
| | - Ying-Jui Chao
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
| | - Yan-Shen Shan
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C
| |
Collapse
|
|
4
|
Tian Y, Lv H, Wang M, Tian Z. A retrospective analysis of lymph node dissection in Siewert II adenocarcinoma of the esophagogastric junction. J Cardiothorac Surg 2024; 19:460. [PMID: 39026299 PMCID: PMC11264608 DOI: 10.1186/s13019-024-02897-3] [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: 01/29/2024] [Accepted: 06/15/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND Analyze the pattern of lymph node metastasis in Siewert II adenocarcinoma of the esophagogastric junction (AEG) and provide a basis for the principles of surgical access. METHODS The clinical data of 112 Siewert type II AEG patients admitted to the Fifth Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2020 to 2022 were retrospectively collected. The probability of lymph node metastasis in each site and the clearance rate of lymph nodes in each site by different surgical approaches were analyzed. RESULTS The lymph node metastasis rates in the middle and upper mediastinum group, the lower mediastinum group, the upper perigastric + supra pancreatic group, and the lower perigastric + hepatoduodenal group were 0.0%, 5.4%, 61.6%, and 17.1%, (P < 0.001). The number of lymph nodes cleared in the middle and upper mediastinum group was 0.00, 0.00, 4.00 in the transabdominal approach (TA), left thoracic approach (LT), and Ivor-Lewis (IL) group, (P < 0.001); The number of lymph nodes cleared in the lower mediastinal group was 0.00, 2.00, 2.00, (P < 0.001); The number of lymph node dissection in the perigastric + hepatoduodenal group was 3.00, 0.00, and 8.00, (P < 0.001). The overall complication rates were 25.7%, 12.5%, and 36.4%, (P = 0.058). CONCLUSION Siewert II AEG has the highest rate of lymph node metastasis in the upper perigastric + supra-pancreatic region, followed by the lower perigastric + hepatoduodenal, lower mediastinal, middle, and upper mediastinal regions. Ivor-Lewis can be used for both thoracic and abdominal lymph node dissection and does not increase the incidence of postoperative complications.
Collapse
Affiliation(s)
- Yang Tian
- Department of Thoracic and Cardiac Surgery, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Hiulai Lv
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO. 12, JianKang Road, Shijiazhuang, China
- Hebei Provincial Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Esophageal Cancer, Hebei, China
| | - Mingbo Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO. 12, JianKang Road, Shijiazhuang, China
- Hebei Provincial Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Esophageal Cancer, Hebei, China
| | - Ziqiang Tian
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO. 12, JianKang Road, Shijiazhuang, China.
- Hebei Provincial Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Esophageal Cancer, Hebei, China.
| |
Collapse
|
|
5
|
Dong H, Yao L, Fan J, Gao P, Yang X, Yuan Z, Zhang T, Lu M, Chen X, Suo C. Characteristics of auto-quantified tumor-infiltrating lymphocytes and the prognostic value in adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, and esophageal squamous cell carcinoma. Aging (Albany NY) 2024; 16:11027-11061. [PMID: 38975889 PMCID: PMC11272125 DOI: 10.18632/aging.205999] [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: 10/04/2023] [Accepted: 06/10/2024] [Indexed: 07/09/2024]
Abstract
BACKGROUND Adenocarcinoma of the esophagogastric junction (AEGJ) with a specific pathological profile and poor prognosis has limited therapeutic options. Previous studies have found that TILs exhibit distinct characteristics in different tumors and are correlated with tumor prognosis. We established cellular training sets to obtain auto-quantified TILs in pathological images. And we compared the characteristics of TILs in AEGJ with those in esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GAC) to gain insight into the unique immune environments of these three tumors and investigate the prognostic value of TILs in these three tumors. METHODS Utilizing a case-control study design, we analyzed 214 AEGJ, 256 GAC, and 752 ESCC cases. The TCGA dataset was used to validate prognostic value of auto-quantified TILs. The specific cellular training sets were established by experienced pathologists to determine TILs counts. Kruskal-Wallis test and multi-variable linear regression were conducted to explore TILs characteristics. Survival analyses were performed with Kaplan-Meier method and Cox proportional hazards model. RESULTS The three cellular training sets of these cancers achieved a classification accuracy of 87.55 at least. The median auto-quantified TILs of AEGJ, GAC, and ESCC cases were 4.82%, 1.92%, and 0.12%, respectively. The TILs demonstrated varied characteristics under distinctive clinicopathological traits. The higher TILs proportion was associated with better prognosis in esophagogastric cancers (all P < 0.05) and was an independent prognostic biomarker on AEGJ in both datasets (Taixing: HR = 0.965, 95% CI = 0.938-0.994; TCGA: HR = 0.811, 95% CI = 0.712-0.925). CONCLUSIONS We found variations in TILs across ESCC, GAC, and AEGJ, as assessed by image processing algorithms. Additionally, TILs in these three cancers are an independent prognostic factor. This enhances our understanding of the unique immune characteristics of the three tumors, improving patient outcomes.
Collapse
Affiliation(s)
- Hao Dong
- Department of Epidemiology and Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China
| | - Longqing Yao
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China
| | - Jiahui Fan
- Department of Clinical Laboratory, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
| | - Peipei Gao
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Xiaorong Yang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China
| | - Ziyu Yuan
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Department of Epidemiology and Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Ming Lu
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China
| | - Chen Suo
- Department of Epidemiology and Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| |
Collapse
|
|
6
|
Tian C, Li Y, Li M. Risk, Predictive Factors, and Nomogram of Liver Metastatic Gastroesophageal Junction Cancer: A New Study Based on the Surveillance, Epidemiology, and End Results Database. Cureus 2024; 16:e63429. [PMID: 39077222 PMCID: PMC11284346 DOI: 10.7759/cureus.63429] [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: 06/28/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Liver metastases are associated with a poor prognosis in gastroesophageal junction (GEJ) cancer patients. The high rate of liver involvement is attributed to the unique anatomical location of the GEJ, which is close to the liver. Patients with liver metastasis typically have advanced, unresectable disease and limited treatment options. Therefore, early detection and prediction are crucial to guide appropriate treatment planning and improve the outcomes for patients with GEJ cancer at risk of liver metastases. Using data from the Surveillance, Epidemiology, and End Results (SEER) database, the present study aimed to elucidate the incidence and risk factors of liver metastases in GEJ cancer patients diagnosed between 2010 and 2019. METHODS This research employed univariable and multivariable logistic regression models to identify risk factors for the development of liver metastases. A predictive nomogram for liver metastases was developed and assessed. Patients' overall survival (OS) with liver metastases was analyzed using the Kaplan-Meier method. RESULTS The study included 1,322 eligible patients with GEJ cancer, 181 (13.6%) of whom were diagnosed with liver metastases. The median overall survival (mOS) for patients with liver metastasis was approximately eight months, compared to a shorter mOS for patients without liver metastasis (P < 0.001). Factors significantly associated with the occurrence of liver metastasis included N3 stage (OR: 1.84; 95% CI: (1.13-2.96); P < 0.001), surgery (OR: 0.09; 95% CI: (0.06-0.14); P < 0.001), lung metastasis (OR: 2.88; 95% CI: (1.78-4.63); P < 0.001), chemotherapy (OR: 0.54; 95% CI: (0.32-0.87); P < 0.001), and radiation therapy (OR: 0.33; 95% CI: (0.25-0.45); P < 0.001). The nomogram demonstrated good performance in predicting liver metastases in GEJ cancer patients (c-index: 0.820). CONCLUSIONS The study identified lymph node status, surgical, lung metastasis, chemotherapy, and radiation as important predictors of outcomes for patients with GEJ cancer. The developed nomogram might be a valuable tool for predicting the risk of liver metastases in GEJ cancer patients, potentially enhancing clinical decision-making processes. By predicting the risk of liver metastasis occurrence, clinicians might intervene in patients with GEJ cancers as early as possible.
Collapse
Affiliation(s)
- Chenrui Tian
- Oncology, Xinxiang Medical University, Xinxiang, CHN
| | - Yang Li
- Oncology, Xinxiang Medical University, Xinxiang, CHN
| | - Min Li
- Pathogenic Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, CHN
| |
Collapse
|
|
7
|
Xu Z, Lin W, Yan S, Chen S, Chen J, Hong Q, Lin H, Xiao L, Zhu J, Bai H, Yu X, You J. The Short-Term and Long-Term Outcomes of Laparoscopy-Assisted Proximal Gastrectomy with Double-Tract Reconstruction versus Laparoscopy-Assisted Total Gastrectomy with Roux-en-Y Reconstruction for Adenocarcinoma of the Esophagogastric Junction: A Multicenter Study Based on Propensity Score Matching Analysis. Gastroenterol Res Pract 2024; 2024:5517459. [PMID: 38882392 PMCID: PMC11178406 DOI: 10.1155/2024/5517459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 11/12/2023] [Accepted: 04/12/2024] [Indexed: 06/18/2024] Open
Abstract
Purpose To compare the antireflux effect, long-term nutritional levels, and quality of life (QoL) between laparoscopy-assisted proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction (LTG-RY) for adenocarcinoma of the esophagogastric junction (AEG). Methods This multicenter retrospective cohort study collected clinicopathological and follow-up data of AEG patients from January 2016 to January 2021 at five high-volume surgery centers. The study included patients who underwent digestive tract reconstruction with LPG-DTR or LTG-RY after tumor resection. Propensity score matching (PSM) was utilized to minimize confounding factors. The comparison after PSM included postoperative complications, reflux esophagitis, long-term nutritional levels, and QoL. Results A total of 151 consecutive patients underwent either LPG-DTR or LTG-RY. After PSM, 50 patients from each group were included in the analysis. The frequency of reflux esophagitis and Clavien-Dindo classification did not significantly differ between the two groups (P > 0.05). At 1 year after surgery, the LPG-DTR group showed significantly higher weight and hemoglobin levels than the LTG-RY group (P < 0.05). The overall postoperative Visick grade differed significantly between the groups (P < 0.05), but there was no significant difference in the proportion of patients with Visick≥III (P > 0.05). Conclusion Both LPG-DTR and LTG-RY are safe and feasible methods for digestive tract reconstruction in patients with AEG. Both methods have similar antireflux effects and postoperative QoL. However, LPG-DTR resulted in superior nutritional levels compared to LTG-RY. Therefore, LPG-DTR is considered a relatively effective method for digestive tract reconstruction in AEG patients.
Collapse
Affiliation(s)
- Zhiwen Xu
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| | - Wei Lin
- Department of Gastrointestinal Surgery The Affiliated Hospital of Putian College, Putian, China
| | - Su Yan
- Department of Gastrointestinal Oncology Surgery The Affiliated Hospital of Qinghai University, Xining, China
| | - Shaoqin Chen
- Department of Gastrointestinal Surgery The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jinping Chen
- Department of Gastrointestinal Surgery The First Hospital of Quanzhou, Quanzhou, China
| | - Qingqi Hong
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| | - Hexin Lin
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| | - Liangbin Xiao
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| | - Jingtao Zhu
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| | - Haoyu Bai
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| | - Xuejun Yu
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| | - Jun You
- Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University, Xiamen, China
| |
Collapse
|
|
8
|
Wang Z, Li X, Hu J, Guo X, Gao B, Zhu B. Bibliometric and visual analysis of esophagogastric junction cancer research from 2002 to 2021. Medicine (Baltimore) 2024; 103:e38100. [PMID: 38758908 PMCID: PMC11098202 DOI: 10.1097/md.0000000000038100] [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: 11/07/2023] [Accepted: 04/11/2024] [Indexed: 05/19/2024] Open
Abstract
Numerous studies related to esophagogastric junction cancer (EGC) have been published, and bibliometric analysis of these publications may be able to identify research hotspots and frontiers of EGC. Studies published on EGC between 2002 and 2021 were retrieved from the Web of Science Core Collection. The collaboration network of countries/regions, institutions, authors, co-citation network of journals, co-occurrence network, and overlay visualization of keywords were analyzed using the VOSviewer software. Cluster and timeline analyses of references were performed using the CiteSpace software. A total of 5109 English articles were published across 691 journals by authors affiliated with 4727 institutions from 81 countries/regions. The annual number of publications related to EGC research has exhibited an increasing trend. The United States, China, and Japan emerged as the top 3 prolific countries/regions. Institutions in the United States, Japan, and South Korea exhibited significant collaboration with one another. Diseases of the Esophagus was the most prolific journal, and Annals of Surgical Oncology, World Journal of Gastroenterology, and Gastric Cancer had also published more than 100 studies. Jaffer A Ajani was the most productive author while David Cunningham ranked the first in terms of total citations and average citations per article. Barrett's esophagus, gastroesophageal reflux disease, Helicobacter pylori, and obesity were common topics in earlier research, and recent years had seen a shift towards the topics of immunotherapy, targeted therapy, and neoadjuvant chemotherapy. In conclusion, growing attention is paid to EGC research, especially in terms of immunotherapy, targeted therapy, and neoadjuvant chemotherapy.
Collapse
Affiliation(s)
- Zhuoyin Wang
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Xinming Li
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Jili Hu
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Xu Guo
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Bulang Gao
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Bin Zhu
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
9
|
Kuang ZY, Sun QH, Cao LC, Ma XY, Wang JX, Liu KX, Li J. Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials. World J Gastrointest Oncol 2024; 16:1046-1058. [PMID: 38577462 PMCID: PMC10989386 DOI: 10.4251/wjgo.v16.i3.1046] [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: 12/21/2023] [Revised: 01/14/2024] [Accepted: 02/04/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.
Collapse
Affiliation(s)
- Zi-Yu Kuang
- Graduate College, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
| | - Qian-Hui Sun
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Lu-Chang Cao
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xin-Yi Ma
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Jia-Xi Wang
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ke-Xin Liu
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Jie Li
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| |
Collapse
|
|
10
|
Tjandra D, Boussioutas A. Li Fraumeni Syndrome predisposes to gastro-esophageal junction tumours. Fam Cancer 2024; 23:29-33. [PMID: 38206485 PMCID: PMC10869364 DOI: 10.1007/s10689-023-00353-0] [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: 08/28/2023] [Accepted: 12/04/2023] [Indexed: 01/12/2024]
Abstract
Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.
Collapse
Affiliation(s)
- Douglas Tjandra
- Familial Cancer Centre, The Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Department of Gastroenterology, Alfred Hospital, 99 Commercial Rd, Melbourne, VIC, 3004, Australia
- Department of Gastroenterology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Alex Boussioutas
- Familial Cancer Centre, The Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
- Department of Gastroenterology, Alfred Hospital, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.
- Department of Gastroenterology, Central Clinical School, Monash University, Melbourne, VIC, Australia.
| |
Collapse
|
|
11
|
Zhou CQ, Gao D, Gui Y, Li NP, Guo WW, Zhou HY, Li R, Chen J, Zhang XM, Chen TW. Computed tomography-based nomogram of Siewert type II/III adenocarcinoma of esophagogastric junction to predict response to docetaxel, oxaliplatin and S-1. World J Radiol 2024; 16:9-19. [PMID: 38312347 PMCID: PMC10835430 DOI: 10.4329/wjr.v16.i1.9] [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: 10/04/2023] [Revised: 12/13/2023] [Accepted: 01/08/2024] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) has become the standard care for advanced adenocarcinoma of esophagogastric junction (AEG), although a part of the patients cannot benefit from NAC. There are no models based on baseline computed tomography (CT) to predict response of Siewert type II or III AEG to NAC with docetaxel, oxaliplatin and S-1 (DOS). AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS. METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS, and were randomly and consecutively assigned to the training cohort (TC) (n = 94) and the validation cohort (VC) (n = 34). Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors (version 1.1) criteria. Possible prognostic factors associated with responses after DOS treatment including Siewert classification, gross tumor volume (GTV), and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age. Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS. A nomogram was established based on independent factors to predict the response. The predictive performance of the nomogram was evaluated by Concordance index (C-index), calibration and receiver operating characteristics curve in the TC and VC. RESULTS Univariate analysis showed that Siewert type (52/55 vs 29/39, P = 0.005), pretherapeutic cT stage (57/62 vs 24/32, P = 0.028), GTV (47.3 ± 27.4 vs 73.2 ± 54.3, P = 0.040) were significantly associated with response to DOS in the TC. Multivariate analysis of the TC also showed that the pretherapeutic cT stage, GTV and Siewert type were independent predictive factors related to response to DOS (odds ratio = 4.631, 1.027 and 7.639, respectively; all P < 0.05). The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC (C-index: 0.838 and 0.824), with area under the receiver operating characteristic curve of 0.838 and 0.824, respectively. The calibration curves showed that the practical and predicted response to DOS effectively coincided. CONCLUSION A novel nomogram developed with pretherapeutic cT stage, GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.
Collapse
Affiliation(s)
- Chuan-Qinyuan Zhou
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Dan Gao
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Yan Gui
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Ning-Pu Li
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Wen-Wen Guo
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Hai-Ying Zhou
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Rui Li
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Jing Chen
- Department of Radiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan Province, China
| | - Xiao-Ming Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Tian-Wu Chen
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| |
Collapse
|
|
12
|
Zhu M, Zhang X, Gao K, Zhang L, Feng X, Wang H, Li J, Jia J. Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/β-catenin Signaling Pathway. Comb Chem High Throughput Screen 2024; 27:611-620. [PMID: 37170988 DOI: 10.2174/1386207326666230426112941] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 02/22/2023] [Accepted: 03/06/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND Structural maintenance of chromosome protein 4 (SMC4) is crucial for chromosome assembly and separation, but its role and mechanism in cardia adenocarcinoma (CA) are unknown. METHODS SMC4 expression levels were initially detected by protein profiling in 20 pairs of CA tumor tissues and adjacent normal tissues. The level of SMC4 expression in CA cells was then evaluated using a western blot analysis. Cell proliferation was evaluated by CCK-8 and clone formation tests. Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the Wnt/β- catenin pathway were investigated using western blot. A tumorigenesis experiment was used to investigate the influence of SMC4 on tumor development in nude mice. RESULTS This study showed overexpression of SMC4 in CA tissues and cells. Knockdown of SMC4 can significantly inhibit the proliferation, migration and invasion, stimulate cell apoptosis, induce cell cycle arrest in the G0/G1 phase of CA cells, and inhibit tumor growth in vivo. In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, β-catenin, phosphorylated GSK-3β, N-cadherin, and Vimentin, with an increased level of proteins, i.e., Bax, cleaved-caspase3, and E-cadherin. When SMC4 was overexpressed, these effects were reversed. CONCLUSION SMC4 can facilitate the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.
Collapse
Affiliation(s)
- Mengqi Zhu
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Xinxin Zhang
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Kaiji Gao
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Lingmei Zhang
- Department of Gynecological Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Xiaojia Feng
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Hui Wang
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Jing Li
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Jianguang Jia
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| |
Collapse
|
|
13
|
Jasani B, Taniere P, Schildhaus HU, Blighe K, Parry S, Wilkinson D, Atkey N, Clare-Antony S, McCabe C, Quinn C, Dodson A. Global Ring Study to Investigate the Comparability of Total Assay Performance of Commercial Claudin 18 Antibodies for Evaluation in Gastric Cancer. J Transl Med 2024; 104:100284. [PMID: 37949357 DOI: 10.1016/j.labinv.2023.100284] [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: 07/28/2023] [Revised: 10/23/2023] [Accepted: 11/06/2023] [Indexed: 11/12/2023] Open
Abstract
Claudin 18.2 (CLDN18.2), the dominant isoform of CLDN18 in gastric tissues, is a highly specific tight junction protein of the gastric mucosa with variably retained expressions in gastric and gastroesophageal junction cancers. Additionally, CLDN18.2-targeted treatment with zolbetuximab, in combination with chemotherapy, has recently been assessed in 2 phase-III studies of patients with HER2-negative, locally advanced, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma. These trials used the investigational VENTANA CLDN18 (43-14A) RxDx immunohistochemistry (IHC) assay on the Ventana BenchMark platform to identify patients eligible for CLDN18.2-targeted treatment. We report the findings of a global ring study evaluating the analytical comparability of concordance of the results of 3 CLDN18 antibodies (Ventana, LSBio, and Novus) stained on 3 IHC-staining platforms (Ventana, Dako, and Leica). A tissue microarray (TMA), comprising 15 gastric cancer cases, was stained by 27 laboratories across 11 countries. Each laboratory stained the TMAs using at least 2 of the 3 evaluated CLDN18 antibodies. Stained TMAs were assessed and scored using an agreed IHC-scoring algorithm, and the results were collated for statistical analysis. The data confirmed a high level of concordance for the VENTANA CLDN18 (43-14A; Ventana platform only) and LSBio antibodies on both the Dako and Leica platforms, with accuracy, precision, sensitivity, and specificity rates all reaching a minimum acceptable ≥85% threshold and good-to-excellent levels of concordance as measured by Cohen's kappa coefficient. The Novus antibody showed the highest level of variability against the reference central laboratory results for the same antibody/platform combinations. It also failed to meet the threshold for accuracy and sensitivity when used on either the Dako or Leica platform. These results demonstrated the reliability of IHC testing for CLDN18 expression in gastric tumor samples when using commercially available platforms with an appropriate methodology and primary antibody selection.
Collapse
Affiliation(s)
- Bharat Jasani
- Discovery Life Sciences (DLS) Biomarker Services GmbH, Kassel, Germany
| | - Philippe Taniere
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Kevin Blighe
- Clinical Bioinformatics Research Ltd, London, UK
| | - Suzanne Parry
- UK National External Quality Assessment Scheme for Immunocytochemistry & In-Situ Hybridisation, London, UK
| | - Dawn Wilkinson
- UK National External Quality Assessment Scheme for Immunocytochemistry & In-Situ Hybridisation, London, UK
| | | | | | | | | | - Andrew Dodson
- UK National External Quality Assessment Scheme for Immunocytochemistry & In-Situ Hybridisation, London, UK
| |
Collapse
|
|
14
|
Zajkowska M, Mroczko B. The Role of Pentraxin 3 in Gastrointestinal Cancers. Cancers (Basel) 2023; 15:5832. [PMID: 38136377 PMCID: PMC10741769 DOI: 10.3390/cancers15245832] [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: 11/10/2023] [Revised: 12/06/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
Gastrointestinal cancers have become a huge problem worldwide as the number of new cases continues to increase. Due to the growing need to explore new biomarkers and therapeutic targets for the detection and treatment of cancerous lesions, we sought to elucidate the role of Pentraxin-3 in the progression of cancerous lesions, as it is involved in the process of angiogenesis and inflammation. Statistically significant changes in the concentration of this parameter have emerged in many gastrointestinal cancer patients. Moreover, it is related to the advancement of cancer, as well as processes leading to the development of those changes. In the case of studies concerning tissue material, both increased and decreased tissue expression of the tested parameter were observed and were dependent on the type of cancer. In the case of cell lines, both human and animal, a significant increase in Pentraxin 3 gene expression was observed, which confirmed the changes observed at the protein level. In conclusion, it can be assumed that PTX3, both at the level of gene expression and protein concentrations, is highly useful in the detection of gastrointestinal cancers, and its use as a biomarker and/or therapeutic target may be useful in the future.
Collapse
Affiliation(s)
- Monika Zajkowska
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland;
| | - Barbara Mroczko
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland;
- Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
| |
Collapse
|
|
15
|
Bîrlă R, Hoara P, Achim F, Dinca V, Ciuc D, Constantinoiu S, Constantin A. Minimally invasive surgery for gastro-oesophageal junction adenocarcinoma: Current evidence and future perspectives. World J Gastrointest Oncol 2023; 15:1675-1690. [PMID: 37969407 PMCID: PMC10631441 DOI: 10.4251/wjgo.v15.i10.1675] [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: 07/05/2023] [Revised: 09/04/2023] [Accepted: 09/22/2023] [Indexed: 10/10/2023] Open
Abstract
Minimally invasive surgery is increasingly indicated in the management of malignant disease. Although oesophagectomy is a difficult operation, with a long learning curve, there is actually a shift towards the laparoscopic/thoracoscopic/ robotic approach, due to the advantages of visualization, surgeon comfort (robotic surgery) and the possibility of the whole team to see the operation as well as and the operating surgeon. Although currently there are still many controversial topics, about the surgical treatment of patients with gastro-oesophageal junction (GOJ) adenocarcinoma, such as the type of open or minimally invasive surgical approach, the type of oesophago-gastric resection, the type of lymph node dissection and others, the minimally invasive approach has proven to be a way to reduce postoperative complications of resection, especially by decreasing pulmonary complications. The implementation of new technologies allowed the widening of the range of indications for this type of surgical approach. The short-term and long-term results, as well as the benefits for the patient - reduced surgical trauma, quick and easy recovery - offer this type of surgical treatment the premises for future development. This article reviews the updates and perspectives on the minimally invasive approach for GOJ adenocarcinoma.
Collapse
Affiliation(s)
- Rodica Bîrlă
- Department of General Surgery, Carol Davila University, Bucharest 011172, Romania
| | - Petre Hoara
- Department of General Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Florin Achim
- Department of General Surgery, Carol Davila University, Bucharest 011172, Romania
| | - Valeriu Dinca
- Faculty of Medicine, “Titu Maiorescu” University, Bucharest 031593, Romania
| | - Diana Ciuc
- Faculty of Medicine, “Titu Maiorescu” University, Bucharest 031593, Romania
| | - Silviu Constantinoiu
- Department of General Surgery, Carol Davila University, Bucharest 011172, Romania
| | - Adrian Constantin
- Department of General Surgery, Carol Davila University, Bucharest 011172, Romania
| |
Collapse
|
|
16
|
Sun CB, Han XQ, Wang H, Zhang YX, Wang MC, Liu YN. Effect of two surgical approaches on the lung function and prognosis of patients with combined esophagogastric cancer. World J Gastrointest Surg 2023; 15:1986-1994. [PMID: 37901732 PMCID: PMC10600760 DOI: 10.4240/wjgs.v15.i9.1986] [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: 05/24/2023] [Revised: 07/04/2023] [Accepted: 07/31/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND Adenocarcinoma of the esophagogastric junction has a center of origin within 5 cm of the esophagogastric junction. Surgical resection remains the main treatment. A transthoracic approach is recommended for Siewert I adenocarcinoma of the esophagogastric junction and a transabdominal approach is recommended for Siewert III adenocarcinoma of the esophagogastric junction. However, there is a need to determine the optimal surgical approach for Siewert II adenocarcinoma of the esophagogastric junction to improve lung function and the prognosis of patients. AIM To investigate and compare the surgical effects, postoperative changes in pulmonary function, and prognoses of two approaches to treating combined esophagogastric cancer. METHODS One hundred and thirty-eight patients with combined esophagogastric cancer treated by general and thoracic surgeries in our hospital were selected. They were divided into group A comprising 70 patients (transabdominal approach) and group B comprising 68 patients (transthoracic approach) based on the surgical approach. The indexes related to surgical trauma, number of removed lymph nodes, indexes of lung function before and after surgery, survival rate, and survival duration of the two groups were compared 3 years after surgery. RESULTS The duration of surgery, length of hospital stay, and postoperative drainage duration of the patients in group A were shorter than those of the patients in group B, and the volume of blood loss caused by surgery was lower for group A than for group B (P < 0.05). At the one-month postoperative review, the first second, maximum ventilation volume, forceful lung volume, and lung volume values were higher for group A than for group B (P < 0.05). Preoperatively, the QLQ-OES18 scale scores of the patients in group A were higher than those in group B on re-evaluation at 3 mo postoperatively (P < 0.05). The surgical complication rate of the patients in group A was 10.00%, which was lower than that of patients in group B, which was 23.53% (P < 0.05). CONCLUSION Transabdominal and transthoracic surgical approaches are comparable in treating combined esophagogastric cancer; however, the former results in lesser surgical trauma, milder changes in pulmonary function, and fewer complications.
Collapse
Affiliation(s)
- Chong-Bing Sun
- Department of General Surgery, Weifang People's Hospital, Weifang 261041, Shandong Province, China
| | - Xiao-Qing Han
- Department of Spinal Surgery, Weifang People's Hospital, Weifang 261041, Shandong Province, China
| | - Hao Wang
- Department of General Surgery, Weifang People's Hospital, Weifang 261041, Shandong Province, China
| | - Yi-Xuan Zhang
- Department of Medical, Weifang People's Hospital, Weifang 261041, Shandong Province, China
| | - Meng-Chun Wang
- Department of General Surgery, Weifang People's Hospital, Weifang 261041, Shandong Province, China
| | - Yong-Ning Liu
- Department of General Surgery, Weifang People's Hospital, Weifang 261041, Shandong Province, China
| |
Collapse
|
|
17
|
Wu K, Li Y, Li Z, Zhou Z, Ge X, Li Y, Han X, Chen P, Ren K. Transcatheter arterial chemoembolization combined with apatinib and camrelizumab for unresectable advanced gastric or gastroesophageal junction cancer: a single-arm, single-center, retrospective study. Front Oncol 2023; 13:1143578. [PMID: 37746269 PMCID: PMC10512224 DOI: 10.3389/fonc.2023.1143578] [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: 01/13/2023] [Accepted: 08/21/2023] [Indexed: 09/26/2023] Open
Abstract
Purpose This study aims to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with Apatinib and Camrelizumab for treating unresectable advanced gastric or gastroesophageal junction (G/GEJ) cancer. Material and methods In this study, data of patients with unresectable advanced G/GEJ cancer who received TACE combined with Apatinib and Camrelizumab from August 2018 to December 2021 was evaluated. After TACE, patients were given intravenous Camrelizumab 200mg every three weeks and oral apatinib 250mg/day for treatment. The primary endpoint was overall survival (OS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results A total of 49 patients were enrolled in this study. The median follow-up time was 14.0 months, and the median OS was 20.0 months (95% CI = 13.6-26.4). Two patients (4.08%) achieved complete remission, 28 patients (57.14%) achieved partial remission, 18 patients (36.73%) had stable disease, and 1 patient (2.04%) had disease progression. The ORR was 61.22%, and the DCR was 97.96%. Multivariate Cox regression analysis indicated that age (HR 4.74, 95% CI = 1.674-13.440, P=0.003) and multiple distant metastases (HR 20.916, 95% CI = 4.094-106.808, P = 0.001) were independent risk factors for OS. Most AEs were classified as grade 1-2, the most common being RCCEP (69.39%). There were 5 cases of grade 3-4 adverse events (10.20%). No patients discontinued or reduced the treatment dose due to AEs, and all patients received symptomatic treatment. Conclusion TACE combined with Apatinib and Camrelizumab is a safe and effective therapeutic option for patients with unresectable advanced G/GEJ cancer, which can significantly improve the median OS and ORR of patients. And the adverse events (AEs) are tolerable and manageable.
Collapse
Affiliation(s)
- Kunpeng Wu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| | - Yahua Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| | - Zongming Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| | - Zihe Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| | - Xiaoyong Ge
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| | - Yifan Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| | - Peng Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Kewei Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, China
| |
Collapse
|
|
18
|
Xu S, Zhu H, Zheng Z. Preoperative Prognostic Nutritional Index Predict Survival in Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction: A Retrospective Study Based on Propensity Score Matching Analyses. Cancer Manag Res 2023; 15:591-599. [PMID: 37431429 PMCID: PMC10329828 DOI: 10.2147/cmar.s415618] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 06/22/2023] [Indexed: 07/12/2023] Open
Abstract
Background This study evaluated the value of PNI to predicting relapse-free survival (RFS) and overall survival (OS) in patients with resectable gastroesophageal junction adenocarcinoma (AGE). Methods Between 2016 and 2020, there were 236 resectable AGE patients underwent a retrospective review via propensity score matched (PSM) analysis. The PNI values were computed for each patient prior to surgery [PNI= 10×albumin (gr/dL) + 0.005×total lymphocyte count (mm3)]. By using disease progression and mortality as the end points, a receiver operating characteristic(ROC) curve was plotted to identify the PNI cut-off value. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. Results The ROC curve indicated that the ideal cutoff value was 45.60. After propensity score matching, there were 143 patients in our retrospective study, which included 58 patients in the low-PNI group and 85 patients in the high-PNI group. When compared to the low PNI group, the high PNI group substantially increased RFS and OS (p<0.001, p=0.003, respectively) according to the Kaplan-Meier analysis and Log rank test. Advanced pathological N stage (p=0.011) and poor PNI (p=0.004) were also significant risk factors for a shorter OS, according to a univariate analysis. Multivariate analysis revealed that the N0 plus N1 group had an endpoint mortality risk that was 0.39 times lower than the N2 plus N3 group's (p=0.008). In comparison to the high PNI group, the hazard of endpoint mortality was 2.442 times greater in the low PNI group (p = 0.003). Conclusion PNI is a simplistic and practical predictive predictor of the RFS and OS time in patients with resectable AGE.
Collapse
Affiliation(s)
- Siqi Xu
- Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
| | - Huide Zhu
- Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
| | - Zhiwei Zheng
- Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
| |
Collapse
|
|
19
|
Xu Z, Chen J, Chen S, Lin H, Zhao K, Zheng C, Liu H, Chen Z, Fu Y, Hong Q, Lin W, Yan S, You J. The clinical outcomes of laparoscopic proximal gastrectomy with double-tract reconstruction versus tube-like stomach reconstruction in patients with adenocarcinoma of the esophagogastric junction based on propensity score-matching: a multicenter cohort study. Front Oncol 2023; 13:1137836. [PMID: 37333809 PMCID: PMC10272833 DOI: 10.3389/fonc.2023.1137836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 05/24/2023] [Indexed: 06/20/2023] Open
Abstract
Purpose Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic proximal gastrectomy with tube-like stomach reconstruction (LPG-TLR) are both function-preserving procedures performed for treating AEG. However, there is no clinical consensus on the selection of digestive tract reconstruction after proximal gastrectomy, and the best way to reconstruct the digestive tract remains controversial. This study aimed at comparing the clinical outcomes of LPG-DTR and LPG-TLR to provide some reference to the choice of AEG surgical modalities. Methods This was a multicenter, retrospective cohort study. we collected clinicopathological and follow-up data of patients with consecutive cases diagnosed with AEG from January 2016 to June 2021 in five medical centers. According to the way of digestive tract reconstruction after tumor resection, patients who underwent LPG-DTR or LPG-TLR were included in the present study. Propensity score matching (PSM) was performed to balance baseline variables that might affect the study outcomes. The QOL of the patients was evaluated using the Visick grade. Results A total of 124 eligible consecutive cases were finally included. Patients in both groups were matched using the PSM method, and 55 patients from each group were included in the analysis after PSM. There was no statistically significant difference between the two groups in terms of the operation time, amount of intraoperative blood loss, days of postoperative abdominal drainage tube placement, postoperative hospitalization days, total hospitalization cost, the total number of lymph nodes cleared, and the number of positive lymph nodes (P>0.05). There was a statistically significant difference between the two groups in terms of time to first flatus after surgery and postoperative soft food recovery time (P<0.05). For the nutritional status, the weight levels at 1 year after surgery was better in the LPG-DTR group than in the LPG-TLR group (P<0.05). There was no significant difference in Visick grade between the two groups (P>0.05). Conclusion The anti-reflux effect and quality of life of LPG-DTR for AEG were comparable to those of LPG-TLR. Compared with LPG-TLR, LPG-DTR provide better nutrition status for patients with AEG. LPG-DTR is a superior reconstruction method after proximal gastrectomy.
Collapse
Affiliation(s)
- Zhiwen Xu
- Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, China
- School of Medicine, Xiamen University, Xiamen, China
| | - Jinping Chen
- Department of Gastrointestinal Surgery, the First Hospital of Quanzhou, Quanzhou, China
| | - Shaoqin Chen
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Hexin Lin
- Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Kang Zhao
- Department of Gastrointestinal Oncology Surgery, the Affiliated Hospital of Qinghai University, Xining, China
| | - Changyue Zheng
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Putian College, Putian, China
| | - Huibin Liu
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Putian College, Putian, China
| | - Zhihua Chen
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yongan Fu
- Department of Gastrointestinal Surgery, the First Hospital of Quanzhou, Quanzhou, China
| | - Qingqi Hong
- Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, China
- School of Medicine, Xiamen University, Xiamen, China
| | - Wei Lin
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Putian College, Putian, China
| | - Su Yan
- Department of Gastrointestinal Oncology Surgery, the Affiliated Hospital of Qinghai University, Xining, China
| | - Jun You
- Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, China
- School of Medicine, Xiamen University, Xiamen, China
| |
Collapse
|
|
20
|
Zhong C, Wu C, Lin Y, Lin D. Refined expression quantitative trait locus analysis on adenocarcinoma at the gastroesophageal junction reveals susceptibility and prognostic markers. Front Genet 2023; 14:1180500. [PMID: 37265963 PMCID: PMC10230079 DOI: 10.3389/fgene.2023.1180500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/03/2023] [Indexed: 06/03/2023] Open
Abstract
Objectives: This study aimed to explore cell type level expression quantitative trait loci (eQTL) in adenocarcinoma at the gastroesophageal junction (ACGEJ) and identify susceptibility and prognosis markers. Methods: Whole-genome sequencing (WGS) was performed on 120 paired samples from Chinese ACGEJ patients. Germline mutations were detected by GATK tools. RNA sequencing (RNA-seq) data on ACGEJ samples were taken from our previous studies. Public single-cell RNA sequencing (scRNA-seq) data were used to produce the proportion of epithelial cells. Matrix eQTL and a linear mixed model were used to identify condition-specific cis-eQTLs. The R package coloc was used to perform co-localization analysis with the public data of genome-wide association studies (GWASs). Log-rank and Cox regression tests were used to identify survival-associated eQTL and genes. Functions of candidate risk loci were explored by experimental validation. Results: Refined eQTL analyses of paired ACGEJ samples were performed and 2,036 potential ACGEJ-specific eQTLs with East Asian specificity were identified in total. ACGEJ-gain eQTLs were enriched at promoter regions more than ACGEJ-loss eQTLs. rs658524 was identified as the top eQTL close to the transcription start site of its paired gene (CTSW). rs2240191-RASAL1, rs4236599-FOXP2, rs4947311-PSORS1C1, rs13134812-LOC391674, and rs17508585-CDK13-DT were identified as ACGEJ-specific susceptibility eQTLs. rs309483-LINC01355 was associated with the overall survival of ACGEJ patients. We explored functions of candidate eQTLs such as rs658524, rs309483, rs2240191, and rs4947311 by experimental validation. Conclusion: This study provides new risk loci for ACGEJ susceptibility and effective disease prognosis biomarkers.
Collapse
Affiliation(s)
- Ce Zhong
- Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chen Wu
- Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Lin
- Beijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, China
| | - Dongxin Lin
- Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
21
|
Ferrari A, Fiocca R, Bonora E, Domizio C, Fonzi E, Angeli D, Domenico Raulli G, Mattioli S, Martinelli G, Molinari C. Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report. Genes (Basel) 2023; 14:genes14040918. [PMID: 37107676 PMCID: PMC10137952 DOI: 10.3390/genes14040918] [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: 03/16/2023] [Revised: 04/06/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
Adenocarcinoma of the esophagus (EAC) and gastroesophageal junction (GEJ-AC) is associated with poor prognosis, treatment resistance and limited systemic therapeutic options. To deeply understand the genomic landscape of this cancer type, and potentially identify a therapeutic target in a neoadjuvant chemotherapy non-responder 48-year-old man, we adopted a multi-omic approach. We simultaneously evaluated gene rearrangements, mutations, copy number status, microsatellite instability and tumor mutation burden. The patient displayed pathogenic mutations of the TP53 and ATM genes and variants of uncertain significance of three kinases genes (ERBB3, CSNK1A1 and RPS6KB2), along with FGFR2 and KRAS high copy number amplification. Interestingly, transcriptomic analysis revealed the Musashi-2 (MSI2)-C17orf64 fusion that has never been reported before. Rearrangements of the RNA-binding protein MSI2 with a number of partner genes have been described across solid and hematological tumors. MSI2 regulates several biological processes involved in cancer initiation, development and resistance to treatment, and deserves further investigation as a potential therapeutic target. In conclusion, our extensive genomic characterization of a gastroesophageal tumor refractory to all therapeutic approaches led to the discovery of the MSI2-C17orf64 fusion. The results underlie the importance of deep molecular analyses enabling the identification of novel patient-specific markers to be monitored during therapy or even targeted at disease evolution.
Collapse
Affiliation(s)
- Anna Ferrari
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, FC, Italy
| | - Roberto Fiocca
- Unit of Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, 16125 Genova, Italy
- Department of Surgical and Diagnostic Sciences (DISC), University of Genova, 16125 Genova, Italy
| | - Elena Bonora
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40126 Bologna, Italy
| | - Chiara Domizio
- Department of Life Sciences and Biotechnology, Ferrara University, 44124 Ferrara, Italy
| | - Eugenio Fonzi
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, FC, Italy
| | - Davide Angeli
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, FC, Italy
| | | | - Sandro Mattioli
- GVM Care & Research Group, Division of Thoracic Surgery-Maria Cecilia Hospital, 48022 Cotignola, RA, Italy
- Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy
| | - Giovanni Martinelli
- Scientific Directorate, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, FC, Italy
| | - Chiara Molinari
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, FC, Italy
| |
Collapse
|
|
22
|
Shao P, Nima S, Tse Y, Suolang Z, Pubu C. Multimodal treatments for resectable esophagogastric junction cancer: A Bayesian network meta-analysis. Langenbecks Arch Surg 2023; 408:123. [PMID: 36934163 DOI: 10.1007/s00423-023-02862-z] [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: 10/09/2022] [Accepted: 03/08/2023] [Indexed: 03/19/2023]
Abstract
PURPOSE To comprehensively investigate the optimal multimodal treatment of resectable esophagogastric junction (EGJ) cancer. METHODS PubMed, Embase, Cochrane Library and Web of Science were searched until March 11, 2022. The outcomes were overall survival (OS), locoregional and distant recurrence, and R0 resection. Network plots, forest plots and league tables were drawn for each outcome. Rank probabilities for different treatments in each outcome were also depicted. RESULTS A total of 23 studies with 18,319 EGJ participants were included. No significant differences in OS between any two of the 6 treatments. Perioperative chemoradiotherapy (pCRT) had the highest probability (36.03%) to be the optimal treatment as regards OS. Patients undergoing pCRT had a significantly lower incidence of locoregional recurrence than those undergoing adjuvant chemotherapy (aCT), neoadjuvant chemotherapy (nCT), perioperative chemotherapy (pCT), or surgery alone (S). Patients with pCRT had the greatest likelihood (68.86%) to have the lowest incidence of locoregional recurrence. Comparable impacts of the 6 treatments on the incidence of distant recurrence, and pCRT was most likely (46.65%) to be the optimal treatment with respect to distant recurrence. Neoadjuvant CRT (nCRT) was associated with a significantly increased incidence of R0 resection compared with nCT or S, and nCRT had the highest probability (97.68%) to be the best therapy regarding R0 resection. CONCLUSION For patients with resectable EGJ cancer, pCRT may be the optimal multimodal treatment regarding survival and recurrence.
Collapse
Affiliation(s)
- Pengfei Shao
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Shazhen Nima
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Yang Tse
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Zhuoma Suolang
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Cangjue Pubu
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China.
| |
Collapse
|
|
23
|
Hu K, Zheng QM, Wang YP, Zhao MM, Sun ZG. Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients. Eur J Cancer Prev 2023; 32:119-125. [PMID: 36484275 DOI: 10.1097/cej.0000000000000776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. METHODS A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. RESULTS In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade ( P = 0.013), infiltration depth ( P = 0.033), and clinicopathological stage ( P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression ( P = 0.037), tumor differentiation ( P = 0.010), lymph node metastasis ( P < 0.001), and clinicopathological stage ( P = 0.037). Tumor differentiation ( P = 0.033) and lymph node metastasis ( P = 0.001) were independent risk factors for shorter overall survival. CONCLUSION E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.
Collapse
Affiliation(s)
- Kang Hu
- Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan
- School of Clinical Medicine, Weifang Medical University, Weifang
| | | | - Ye-Peng Wang
- Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan
| | - Meng-Meng Zhao
- Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Zhi-Gang Sun
- Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan
| |
Collapse
|
|
24
|
Piva VM, De Grandis MC, Zuin IS, Angerilli V, Nappo F, Alfieri R, Ahcene Djaballah S, Murgioni S, Bergamo F, Fassan M, Valmasoni M, Lonardi S. ctDNA as promising tool for the assessment of minimal residual disease (MRD) and the need of an adjuvant treatment in gastroesophageal adenocarcinoma. Updates Surg 2023; 75:305-312. [PMID: 36272058 DOI: 10.1007/s13304-022-01379-2] [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: 03/29/2022] [Accepted: 09/12/2022] [Indexed: 01/24/2023]
Abstract
Gastroesophageal adenocarcinoma is a challenging disease due to its poor prognosis and the presence of few therapeutic options. For these reasons, it is mandatory to identify the subgroup of patients who are at high risk for relapse after curative-intention surgery. In the last years, liquid biopsy has aroused great interest in cancer treatment for its feasibility and the possibility to capture tumor heterogeneity in a real-time way. In postoperative setting, the interest is directed to the identification of Minimal Residual Disease (MRD), defined as isolated or small cluster of cancer cells that residues after curative-intention surgery, and are undetectable by conventional radiological and clinical exams. This review wants to summarize current evidence on the use of liquid biopsy in gastroesophageal cancer, focusing on the detection of ctDNA in the postoperative setting and its potential role as a guide for treatment decision.
Collapse
Affiliation(s)
- Vittoria Matilde Piva
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Maria Caterina De Grandis
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Irene Sole Zuin
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Surgery Clinic 1, Padova University Hospital, Padua, Italy
| | - Valentina Angerilli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Floriana Nappo
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Rita Alfieri
- Unit of Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Selma Ahcene Djaballah
- Medical Oncology 3, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128, Padua, Italy
| | - Sabina Murgioni
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Francesca Bergamo
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Michele Valmasoni
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Surgery Clinic 1, Padova University Hospital, Padua, Italy
| | - Sara Lonardi
- Medical Oncology 3, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128, Padua, Italy.
| |
Collapse
|
|
25
|
Fu J, Li Y, Liu X, Jiao X, Qu H, Wang Y, Niu Z. Effects of robotic and laparoscopic-assisted surgery on lymph node dissection and quality of life in the upper third of gastric cancer: A retrospective cohort study based on propensity score matching. Front Surg 2023; 9:1057496. [PMID: 36684301 PMCID: PMC9845627 DOI: 10.3389/fsurg.2022.1057496] [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: 09/29/2022] [Accepted: 11/21/2022] [Indexed: 01/05/2023] Open
Abstract
Objective The objective of this study was compare the effects of robot-assisted and laparoscopic-assisted surgery on lymph node dissection and quality of life in upper third gastric cancer patients undergoing radical total gastrectomy. Methods The clinical and follow-up data of 409 patients with upper third gastric cancer who underwent total gastrectomy from July 2016 to May 2021 were enrolled. The patients were divided into a robotic group (n = 106) and a laparoscopic group (n = 303). Age, sex, body mass index, American Society of Anesthesiologists score, tumor size and location, pathological type, cT, cN, and cTNM were adjusted to offset selection bias. The patient characteristics, operative procedures, surgical outcomes, oncologic and pathologic outcomes, number of lymph node dissections, quality of life assessment, and nutritional status were compared between the two groups. Results After propensity score matching, 61 cases were included in the robotic group and 122 cases were included in the laparoscopic group. The number of dissected lymph nodes (37.3 ± 13.5 vs. 32.8 ± 11.8, P = 0.022) significantly differed between the two groups. The number of lower mediastinal and subphrenic lymph nodes in the robotic group was greater than that in the laparoscopic group, and the difference was statistically significant (P < 0.001). Compared with the laparoscopic group, the total score of physical symptoms in the robotic group was significantly lower at 6 and 12 months after surgery (P = 0.03 and P = 0.001, respectively). The total social function score at 6 and 12 months after surgery was higher in the robotic group (P = 0.006 and P = 0.022). The quality of life scores were statistically significant only at 3 months after the operation (P = 0.047). A higher patient-generated subjective global assessment (PG-SGA) score is when the score significantly correlated (P < 0.001) with a higher related physical symptoms score, lower social function score, and lower quality of life score. Conclusion Compared with laparoscopic radical gastrectomy, robotic radical gastrectomy is safe and feasible. Compared with laparoscopic radical gastrectomy, robotic radical gastrectomy was more refined, was associated with less surgical bleeding, and increased the quality of lymph node dissection. In addition, patients in the robotic group showed better postoperative quality of life.
Collapse
|
|
26
|
Ghezzi A, Rossi J, Cavallieri F, Napoli M, Pascarella R, Rizzi R, Russo M, Salomone G, Romano A, Iaccarino C, Froio E, Serra S, Cozzi S, Giaccherini L, Valzania F, Pisanello A. Case Report: Pituitary metastasis as a presenting manifestation of silent gastric cardia adenocarcinoma. Front Oncol 2023; 12:1059361. [PMID: 36686817 PMCID: PMC9846627 DOI: 10.3389/fonc.2022.1059361] [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: 10/01/2022] [Accepted: 12/05/2022] [Indexed: 01/06/2023] Open
Abstract
Introduction Pituitary metastases are very rare in cancer patients and often originate from lung or breast tumors. They usually occur in patients with known metastatic disease, but rarely may be the first presentation of the primary tumor. Methods We present the case of a 58 years-old-man who reported a three-month history of polyuria-polydipsia syndrome, generalized asthenia, panhypopituitarism and bitemporal hemianopsia. Brain-MRI showed a voluminous pituitary mass causing posterior sellar enlargement and compression of the surrounding structures including pituitary stalk, optic chiasm, and optic nerves. Results The patient underwent neurosurgical removal of the mass. Histological examination revealed a poorly differentiated adenocarcinoma of uncertain origin. A total body CT scan showed a mass in the left kidney that was subsequently removed. Histological features were consistent with a clear cell carcinoma. However, endoscopic examination of the digestive tract revealed an ulcerating and infiltrating adenocarcinoma of the gastric cardia. Total body PET/CT scan with 18F-FDG confirmed an isolated area of accumulation in the gastric cardia, with no hyperaccumulation at other sites. Conclusion To the best of our knowledge, there are no reports of pituitary metastases from gastric cardia adenocarcinoma. Our patient presented with symptoms of sellar involvement and without evidence of other body metastases. Therefore, sudden onset of diabetes insipidus and visual deterioration should lead to the suspicion of a rapidly growing pituitary mass, which may be the presenting manifestation of a primary extracranial adenocarcinoma. Histological investigation of the pituitary mass can guide the diagnostic workup, which must however be complete.
Collapse
Affiliation(s)
- Andrea Ghezzi
- Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Jessica Rossi
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy,Neuromotor & Rehabilitation Department, Neurology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy,*Correspondence: Jessica Rossi,
| | - Francesco Cavallieri
- Neuromotor & Rehabilitation Department, Neurology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Manuela Napoli
- Neuroradiology Service, Department of Diagnostic Imaging and Laboratory Medicine, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Rosario Pascarella
- Neuroradiology Service, Department of Diagnostic Imaging and Laboratory Medicine, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Romana Rizzi
- Neuromotor & Rehabilitation Department, Neurology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Marco Russo
- Neuromotor & Rehabilitation Department, Neurology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Gaetano Salomone
- Neuromotor & Rehabilitation Department, Neurology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Antonio Romano
- Neurosurgery Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Corrado Iaccarino
- Neurosurgery Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Elisabetta Froio
- Pathological Anatomy Service, Oncology Department and Advanced Technologies, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Silvia Serra
- Pathological Anatomy Service, Oncology Department and Advanced Technologies, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Salvatore Cozzi
- Radiation Oncology Unit, Oncological Department and Advanced Technologies, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Lucia Giaccherini
- Radiation Oncology Unit, Oncological Department and Advanced Technologies, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Franco Valzania
- Neuromotor & Rehabilitation Department, Neurology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Anna Pisanello
- Neuromotor & Rehabilitation Department, Neurology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| |
Collapse
|
|
27
|
Imbrasaitė U, Giršvildaitė D, Baušys R, Baušys A. Surgical Treatment of Siewert II Gastroesophagel Junction Adenocarcinoma: Esophagectomy or Gastrectomy? Review. LIETUVOS CHIRURGIJA 2022. [DOI: 10.15388/lietchirur.2022.21.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Introduction. Surgery is the only curative treatment option for patients with gastroesophageal junction (GEJ) adenocarcinoma. These tumors can be resected by gastrectomy or esophagectomy depending on tumor localization. Although, both surgeries are available for Siewert type II GEJ cancer, it remains unknown which one is superior. This review summarizes current evidences on the optimal surgical approach for Siewert type II GEJ adenocarcinoma. Methods. The literature search was performed within the PubMed database and 9 studies comparing gastrectomy and esophagectomy for Siewert type II GEJ adenocarcinoma were included. The outcomes of interest included: length of surgery, numbers of retrieved lymph nodes, resection margins, postoperative morbidity and mortality, hospitalization time, 5-year overall, and disease-free survival rates. Results. Current studies do not favor any type of surgery in terms of length of the surgery, R0 resection rate, or postoperative morbidity. There is some tendency towards higher anastomotic leakage and postoperative surgical site infections rate after gastrectomy, while a higher incidence of pneumonia after esophagectomy. Similar, available studies suggest, that esophagectomy may lead to improved long-term outcomes. Conclusions. There is a lack of high-quality studies comparing gastrectomy and esophagectomy for Siewert type II GEJ adenocarcinoma. Esophagectomy may lead to improved long-term outcomes, but this preliminary data has to be confirmed in large, randomized control trials.
Collapse
|
|
28
|
Lamture Y, Gharde P, Gajbhiye V, Nagtode T, Mastud K, Kulkarni V, Patel D. Adenocarcinoma of the Stomach With Situs Inversus Totalis: A Rare Case. Cureus 2022; 14:e31538. [DOI: 10.7759/cureus.31538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 11/15/2022] [Indexed: 11/16/2022] Open
|
|
29
|
Gu L, Huang T, Qiu S, Hong J, Fu R, Ni C, Dai S, Chen P, He N. Efficacy of PD-1/PD-L1 inhibitors in patients with advanced gastroesophageal cancer: An updated meta-analysis based on randomized controlled trials. Front Pharmacol 2022; 13:1009254. [PMID: 36386140 PMCID: PMC9640921 DOI: 10.3389/fphar.2022.1009254] [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: 08/02/2022] [Accepted: 10/10/2022] [Indexed: 12/24/2022] Open
Abstract
Background: This study aimed to investigate the clinical efficacy of programmed death-1 receptor and ligand-1 (PD-1/PD-L1) inhibitors in gastroesophageal cancer patients and the relationship between their clinicopathological features and curative treatment effects. Methods: A systematic search was conducted for articles published before April 2022 from online databases (PubMed, EMBASE, Web of Science and the Cochrane Library). The main outcome was overall survival (OS). Results: This meta-analysis comprised 16 studies involving 9,304 participants. The results indicated that compared with chemotherapy, patients treated with PD-1/PD-L1 inhibitors had significantly improved OS (HR = 0.80; p < 0.001) but no significant improvement in progression-free survival (PFS) (p = 0.185). Subgroup analyses demonstrated that PD-1/PD-L1 inhibitors combined with chemotherapy, esophageal squamous cell carcinoma, male, Asian patients and combined positive score (CPS) ≥1 were significantly associated with better survival outcomes. Further, subgroup analysis of gender revealed that the OS of all subgroups containing male patients was significantly improved compared with chemotherapy, unlike that of female patients. In addition, the line of therapy, Lauren classification, age and eastern cooperative oncology group (ECOG) performance status were not associated with PD-1/PD-L1 inhibitors efficacy. Conclusion: The results indicated that PD-1/PD-L1 inhibitors could prolong the OS of advanced gastroesophageal cancer patients. Clinicopathological features such as therapeutic schedules, tumor types, histological type, gender, geographical region and PD-L1 expression status (CPS) seemed to be associated with survival outcomes.
Collapse
Affiliation(s)
- Lihu Gu
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo No. 2 Hospital, Ningbo, China
| | - Tongmin Huang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Shinan Qiu
- Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Rongrong Fu
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Chaoxiong Ni
- Department of Nephrology, QingChun Hospital of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Senjie Dai
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Ping Chen
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo No. 2 Hospital, Ningbo, China
| | - Ning He
- Department of Tumor High-Intensity Focused Ultrasound (HIFU) Therapy, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
- *Correspondence: Ning He,
| |
Collapse
|
|
30
|
Whether the infracardiac bursa protect right pleura during laparoscopic radical operation of Siewert type II adenocarcinoma of esophagogastric junction? BMC Cancer 2022; 22:927. [PMID: 36030215 PMCID: PMC9419360 DOI: 10.1186/s12885-022-10024-5] [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: 05/15/2022] [Accepted: 08/22/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Transthoracic single-port assisted laparoscopic five-step maneuver inferior mediastinal lymphadenectomy for Siewert type II adenocarcinoma of esophagogastric junction (AEG) has superiority in lower mediastinal lymph nodes dissection and digestive tract reconstruction. However, the right pleura was probably ruptured in this surgical technique. The aim of this study was to explore whether the infracardiac bursa (ICB) exposed could protect right pleura. METHODS We retrospectively collected and evaluated the clinical and pathological data of patients who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymphadenectomy for Siewert II AEG at Guangdong Provincial Hospital of Chinese Medicine between May 2017 and February 2022. RESULTS A total of 49 patients were eligible, including 31 patients in ICB exposed group (group A) and 18 patients in ICB unexposed group (group B). There were no statistically significant differences in baseline characteristics between the two groups. 4 patients (12.9%) had right pleura rupture in group A, while 14 patients (77.8%) in group B, and the difference was statistically significant (p < 0.001). Compared with group B, the extubation time of endotracheal intubation (10.0 (6.0 ~ 12.0) vs. 13.0 (8.0 ~ 15.0) min, p = 0.003) and thoracic drainage tube stay (6.0 (5.0 ~ 7.0) vs. 8.0 (6.0 ~ 10.5) days, p = 0.041) were significantly shorted in the group A. The drainage volume of thorax (351.61 ± 125.00 vs. 418.61 ± 207.86 mL, p = 0.146) was non-significant less and the rate of complications (3.2% vs. 11.1%, p = 0.074) was non-significant lower in group A compared with group B. The postoperative hospital stay (9.0 (8.0,13.0) vs. 9.0 (8.0,12.0) days, p = 0.983) were similar in two groups. No serious adverse event occurred in any patient. CONCLUSIONS The ICB exposed could protect the right pleura and may promote postoperative recovery, which may be used as an anatomical marker in inferior mediastinal lymphadenectomy.
Collapse
|
|
31
|
Zheng YH, Zhao EH. Recent advances in multidisciplinary therapy for adenocarcinoma of the esophagus and esophagogastric junction. World J Gastroenterol 2022; 28:4299-4309. [PMID: 36159003 PMCID: PMC9453767 DOI: 10.3748/wjg.v28.i31.4299] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/22/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) and adenocarcinoma of the esophagogastric junction (EGJA) have long been associated with poor prognosis. With changes in the spectrum of the disease caused by economic development and demographic changes, the incidence of EAC and EGJA continues to increase, making them worthy of more attention from clinicians. For a long time, surgery has been the mainstay treatment for EAC and EGJA. With advanced techniques, endoscopic therapy, radiotherapy, chemotherapy, and other treatment methods have been developed, providing additional treatment options for patients with EAC and EGJA. In recent decades, the emergence of multidisciplinary therapy (MDT) has enabled the comprehensive treatment of tumors and made the treatment more flexible and diversified, which is conducive to achieving standardized and individualized treatment of EAC and EGJA to obtain a better prognosis. This review discusses recent advances in EAC and EGJA treatment in the surgical-centered MDT mode in recent years.
Collapse
Affiliation(s)
- Yi-Han Zheng
- Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - En-Hao Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| |
Collapse
|
|
32
|
Wang L, Chen X, Miao W, Ma Y, Ma X, Wang C, Cao X, Xu H, Wei J, Yan S. Total laparoscopic versus laparoscopic-assisted transabdominal posterior mediastinal digestive tract reconstruction in the treatment of Siewert II adenocarcinoma of the esophagogastric junction: A retrospective study. Front Surg 2022; 9:874857. [PMID: 36061040 PMCID: PMC9437538 DOI: 10.3389/fsurg.2022.874857] [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: 02/13/2022] [Accepted: 07/07/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The method of operation and the range of resection for Siewert II adenocarcinoma of the esophagogastric junction (AEG) remain controversial. This study aims to evaluate the safety, feasibility, and short-term postoperative effect of total laparoscopic versus laparoscopic-assisted transabdominal posterior mediastinal digestive tract reconstruction in the treatment of Siewert II AEG. METHODS Total laparoscopic or laparoscopic-assisted gastrointestinal reconstruction through abdominal posterior mediastinum was performed in 108 patients with Siewert II AEG from October 2017 to February 2019. This study evaluated the loss of intraoperative blood, the number of lymph nodes, the marginal of the tumor, short-term postoperative complications (within 30 days), the rate of survival at follow-up, and the economic cost, feasibility, and effect of short-term postoperative recovery for patients who received these two operations. RESULT There were no significant differences in general data between the total laparoscopic group and the laparoscopic-assisted group (P > 0.05). However, the total laparoscopic group cost more time on the surgical procedure and digestive tract reconstruction, lost less intraoperative blood, and had more mediastinal lymph nodes compared with the laparoscopic-assisted group (P < 0.05). The total laparoscopic group was significantly better than the laparoscopic-assisted group compared with the short-term postoperative recovery indexes, such as the first exhaust time, the first defecation time, the first fluid time, the first semi-fluid diet time, the postoperative hospital stay, and other postoperative recovery indexes (P < 0.05). In addition, there were no significant differences in postoperative complications, postoperative pathological indexes, the recurrence rate, and mortality between the total laparoscopic group and laparoscopic-assisted group (P > 0.05). CONCLUSIONS The safety, feasibility, and short-term effect of total laparoscopic transabdominal posterior mediastinal digestive tract reconstruction in the treatment of Siewert II AEG were better than those for the laparoscopic-assisted group.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Su Yan
- Department of Gastrointestinal Oncology, Qinghai University Affiliated Hospital, Xining, China
| |
Collapse
|
|
33
|
Singhartinger FX, Wahl L, Weitzendorfer M, Gantschnigg A, Koch OO, Emmanuel K. The role of hormones in symptoms and pathophysiology of reflux and esophageal motility disorders. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022. [PMID: 35697064 DOI: 10.1055/a-1833-9494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
PURPOSE A few studies suggest that hormones play a role in the motility of the lower esophagus, but data is rare. In this prospective study we evaluated the correlation between hormones (TSH, fT3, fT4, calcitonin, gastrin, and VIP) and gastroesophageal reflux disease (GERD), esophageal motility disorders, and gastrointestinal symptoms. METHODS 100 consecutive patients with reflux symptoms and dysphagia were hospitalized for diagnostic evaluation. Self-reporting questionnaires were handed out and patients routinely underwent serum analysis (TSH, fT3, fT4, calcitonin, gastrin, and VIP), 24-hour-pH-impendance monitoring, and high-resolution manometry. RESULTS Motility disorders were found in 38 out of 86 patients. There were no correlations between hormones, the DeMeester Score, and the lower esophageal sphincter pressure. A strong inverse relation between calcitonin and the Integrated Relaxation Pressure of the esophagogastric junction was found (r=-0.492; p<0.001). No correlations were found between hormone levels and the responses given in the questionnaires. Positive correlations, however, were found between VIP and gastrointestinal symptoms, as well as correlations between fT3 and dysphagia. Within the group with minor motility disorders, TSH and fT4 correlated with outcomes of the SCL-questionnaire. fT4 correlated with the typical symptoms, as well as the gastrointestinal symptoms (diarrhea, constipation, flatulence). TSH correlated with the typical symptoms. Moreover, a correlation between VIP and gas-bloat-symptoms was found within group II CONCLUSIONS: No correlation between TSH, fT3, fT4, gastrin, VIP, calcitonin, and GERD in the sense of acid reflux was found, although calcitonin seems to have an effect on the lower esophageal sphincter.
Collapse
Affiliation(s)
| | - Lisa Wahl
- Internal Medicine, Salzkammergut-Klinikum Gmunden, Gmunden, Austria
| | | | | | - Oliver Owen Koch
- Department for Surgery, University Hospital Salzburg, Salzburg, Austria
| | - Klaus Emmanuel
- Department for Surgery, University Hospital Salzburg, Salzburg, Austria
| |
Collapse
|
|
34
|
Successful robotic proximal gastrectomy with side overlap esophagogastrostomy following preoperative chemotherapy: A case report. Int J Surg Case Rep 2022; 94:107040. [PMID: 35658273 PMCID: PMC9171439 DOI: 10.1016/j.ijscr.2022.107040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/02/2022] [Accepted: 04/03/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction and importance Adenocarcinoma of the esophagogastric junction (AEJ) has been on the rise in recent years, but the technical aspects of reconstruction and reflux prevention are unsolved problems. This case report aimed to illustrate the usefulness of preoperative chemotherapy for tumor shrinkage and the advantage of robotic surgery for stable reconstruction with reflux prevention. Case presentation A 69-year-old male patient was diagnosed with AEJ cT3N0M0 cStage IIB. Three courses of doublet chemotherapy with 80 mg/m2/day of S-1 on days 1–14 and 100 mg/m2 of oxaliplatin on day 1 were administered every 3 weeks before surgery. After chemotherapy, the tumor shrunk, and the proximal margin changed from 1.5 cm above the esophagogastric junction (EGJ) to be the gastric side of the EGJ. A radical robotic proximal gastrectomy with D2 lymphadenectomy was performed. Since sufficient length of the esophagus was secured in the hiatus due to tumor shrinkage, reconstruction was performed by the side-overlap esophagogastrostomy (mSOFY) method. The postoperative course was uneventful with no reflux symptoms two months after surgery, even without medication. Clinical discussion Preoperative chemotherapy is expected to improve the rates of complete resection and survival. In the present case, preoperative treatment with SOX resulted in tumor shrinkage, which enabled reconstruction using the mSOFY method. Robotic surgery may be useful for such complex reconstruction procedures. Conclusion To our knowledge, this is the first report of robotic reconstruction using the mSOFY method after proximal gastrectomy for AEG tumors. This work was reported in line with the SCARE 2020 criteria.
Preoperative chemotherapy is useful for tumor shrinkage in patients with AEJ. Robotic mSOFY reconstruction enables reliable hand movement and good field of view. Robotic mSOFY can improve QOL and prevent reflux after proximal gastrectomy.
Collapse
|
|
35
|
20-Year Trends in Detection Rates of Cardia Cancer via Endoscopic Surveillance in Tianjin, China: A Hospital-Based Study. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:1505655. [PMID: 35422872 PMCID: PMC9005319 DOI: 10.1155/2022/1505655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/06/2022] [Accepted: 03/19/2022] [Indexed: 12/24/2022]
Abstract
Background To analyze the time trends in cardia cancer detection rates using endoscopic surveillance from 1999 to 2019 in a high-volume Chinese hospital. Methods In this retrospective, single-center study, data were collected from the Endoscopy Center of the Department of Gastroenterology, Tianjin Medical University General Hospital, from 1999 to 2019. Cases of cardia cancer (n = 1567) were extracted from a database of patients who underwent endoscopy. Clinical and epidemiological characteristics of patients with cardia cancer were analyzed, including sex, age, and proportion of early gastric cancer and degree of tumor differentiation. The joinpoint regression method was used to identify change points in incidence trends. Annual percent change (APC) values, with 95% confidence intervals (CI), were calculated for time periods before and after change points. Results Of the 343942 patients who underwent endoscopy during 1999–2009, 1567 (4.6%) were identified with cardia cancer. The overall cardia adenocarcinoma detection rate decreased significantly from 1999 to 2004 (APC = −37.3, 95% CI: -20.9, -6.4), followed by a relatively slower decline rate from 2004 to 2019 (APC = −7.7, 95% CI: -4.4, -7.6). The crude rate of detection of early cardia cancer could not be determined by joinpoint analysis. Rates of detection reduced significantly in patients aged 60–69 and 70-79 years (APC = −8.3, 95% CI: -9.8, -6.8 and APC = −7.3, 95% CI: -8.8, -5.8, respectively). The detection rate in males decreased rapidly from 1999 to 2004 (APC = −35.9, 95% CI: -18.2, 5.6, P < 0.05), while the decline rate was relatively slow from 2005 to 2019 (APC = −6.9, 95% CI: -3.4, -6.1, P < 0.05). Among females, the detection rates also decreased from 1999 to 2004 (APC = −21.2, 95% CI: -28.1, -13.7), but remained stable from 2007 to 2019 (APC = −3.8, 95% CI: -7.9, -0.5). Detection of poorly differentiated cardia cancer also declined from 2009 to 2019 (APC = −12.8, 95% CI: -15.3, -10.0). Conclusions The detection rate of cardia cancer among gastric cancers has been stable from 2008 to 2019. The trend of detection rate of early cardia cancer showed no significant statistical meaning; hence, it remains necessary to carefully observe the cardia area during endoscopy examination.
Collapse
|
|
36
|
Schlottmann F, Casas MA, Molena D. Evidence-based approach to the treatment of esophagogastric junction tumors. World J Clin Oncol 2022; 13:159-167. [PMID: 35433293 PMCID: PMC8966513 DOI: 10.5306/wjco.v13.i3.159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Revised: 06/14/2021] [Accepted: 02/15/2022] [Indexed: 02/06/2023] Open
Abstract
The incidence of esophagogastric junction (EGJ) adenocarcinoma is increasing in developed nations due to the rising prevalence of obesity and gastroesophageal reflux disease. Due to the peculiar location in a histological transition zone between the esophagus and the stomach, the management of EGJ tumors is controversial. Two main surgical approaches exist: total gastrectomy with distal esophagectomy or esophagectomy by either transhiatal or transthoracic approach. These operations differ significantly in the extent of lymphadenectomy. In addition, patients with locally advanced disease can receive either preoperative chemoradiation or perioperative chemotherapy. This evidence-based review analyzes current evidence regarding the management of EGJ tumors in order to help defining the best surgical and systemic treatment of these patients.
Collapse
Affiliation(s)
- Francisco Schlottmann
- Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires C1118AAT, Argentina
| | - María A Casas
- Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires C1118AAT, Argentina
| | - Daniela Molena
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
| |
Collapse
|
|
37
|
Takeuchi M, Kawakubo H, Matsuda S, Mayanagi S, Irino T, Okui J, Fukuda K, Nakamura R, Wada N, Takeuchi H, Kitagawa Y. Association of anastomotic leakage with long-term oncologic outcomes of patients with esophagogastric junction cancer. World J Gastrointest Surg 2022; 14:46-55. [PMID: 35126862 PMCID: PMC8790330 DOI: 10.4240/wjgs.v14.i1.46] [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: 03/25/2021] [Revised: 06/29/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Despite improvements in surgical procedures and peri-operative patients management, the postoperative complications in esophagogastric junction (EGJ) cancer remain high because of technical aspects. Several studies have indicated the negative influence of postoperative infectious complications on long-term survival after gastrointestinal surgery. However, no study has shown the association between postoperative complications and long-term survival of patients with EGJ cancer.
AIM To elucidate influence of postoperative complications on the long-term outcomes of patients with EGJ cancer.
METHODS A total of 122 patients who underwent surgery for EGJ cancer at the Keio University were included in this study. We examined the association between complications and long-term oncologic outcomes.
RESULTS In all patients, the 3-year overall survival (OS) rate was 71.9%, and the recurrence-free survival (RFS) rate was 67.5%. Compared with patients without anastomotic leakage, those with anastomotic leakage had poor median OS (8 mo vs not reached, P = 0.028) and median RFS (5 mo vs not reached, P = 0.055). Among patients with cervical anastomosis, there were not significant differences between patients with and without anastomotic leakage. However, among patients who underwent intrathoracic anastomosis, patients with anastomotic leakage had significantly worse OS (P = 0.002) and RFS (P = 0.005).
CONCLUSION Anastomotic leakage was significantly associated with long-term oncologic outcomes of patients with EGJ cancer, especially those who underwent intrathoracic anastomosis. Cervical anastomosis with subtotal esophagectomy may be an option for the patients who are at high risk for anastomotic leakage.
Collapse
Affiliation(s)
- Masashi Takeuchi
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Satoru Matsuda
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Shuhei Mayanagi
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Tomoyuki Irino
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Jun Okui
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kazumasa Fukuda
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Rieko Nakamura
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Norihito Wada
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| |
Collapse
|
|
38
|
Liu X, Jiang Q, Yue C, Wang Q. Clinicopathological Characteristics and Survival Predictions for Adenocarcinoma of the Esophagogastric Junction: A SEER Population-Based Retrospective Study. Int J Gen Med 2022; 14:10303-10314. [PMID: 34992445 PMCID: PMC8714080 DOI: 10.2147/ijgm.s341405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022] Open
Abstract
Objective Adenocarcinoma of the esophagogastric junction (AEJ) is a relatively rare malignancy in Western countries whose specific clinicopathological characteristics and associated prognosis have not been comprehensively described. Methods Data on patients with AEJ between 2005 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were extracted, evaluated, and compared with patients with gastric cancer (GC) in general. Overall survival (OS) was evaluated using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify risk factors predictive for OS, and the results were used to construct a nomogram to predict 1-, 3-, and 5-year OS among patients with AEJ. Results A total of 8013 patients diagnosed with AEJ were identified from the records of 30,179 patients with GC. The mean age was 65.4 (SD = 12.0) years, 79.5% were men, 87.2% were Caucasian, 91.5% were moderately-to-poorly differentiated, 34.4% had AJCC stage I AEJ, and 28.8% had stage IV. The median OS was 18 months, and the 5-year OS was 25.8% (95% CI: 24.8–26.8%). Fewer patients with AEJ had undergone surgical resection, fewer had T+ and N+ (N2~N3) disease (P < 0.001), and fewer had distant metastases compared to the patients with GC (P < 0.05). In the univariate and multivariate analyses, age, race, summary stage, N stage, M stage, and surgery were identified as independent risk factors. The nomogram had a calibration index of 0.726. Conclusion AEJ was found to have distinct clinicopathological characteristics. Age, race, summary stage, N stage, M stage, and surgery were independently associated with OS. The nomogram accurately predicted 1-, 3-, and 5-year OS rates.
Collapse
Affiliation(s)
- Xin Liu
- Department of Prevention and Control for Occupational Disease, Jiangsu Provincial Center for Disease Control and Prevention & Jiangsu Preventive Medicine Association, Nanjing, People's Republic of China
| | - Qingtao Jiang
- Department of Clinical Medicine, Jiangsu Health Vocational College, Nanjing, People's Republic of China
| | - Chao Yue
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Qin Wang
- Department of Clinical Medicine, Jiangsu Health Vocational College, Nanjing, People's Republic of China
| |
Collapse
|
|
39
|
Xiong J, Kang W, Ma F, Liu H, Ma S, Li Y, Jin P, Hu H, Tian Y. Modified Systemic Inflammation Score Is an Independent Predictor of Long-Term Outcome in Patients Undergoing Surgery for Adenocarcinoma of the Esophagogastric Junction. Front Surg 2021; 8:622821. [PMID: 34820414 PMCID: PMC8606684 DOI: 10.3389/fsurg.2021.622821] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Accepted: 10/05/2021] [Indexed: 12/14/2022] Open
Abstract
Background: The modified systemic inflammation score (mSIS), which is calculated by a composite score of the lymphocyte-to-monocyte ratio and the albumin content in serum, is identified as the new score to predict the prognosis for various cancers. However, its significance for patients with adenocarcinoma of esophagogastric junction (AEJ), who receive surgery, remains unclear. Methods: This study retrospectively analyzed 317 patients with AEJ receiving surgery between September 2010 and December 2016. The associations between the mSIS and the clinicopathological features, overall survival (OS), as well as relapse-free survival (RFS), were assessed. In addition, the time-dependent receiver operating characteristic (t-ROC) curve analysis was performed for comparing the value of those scoring systems in predicting patient prognosis. Results: Of the 317 cases, 119 were rated as mSIS 0, 123 as mSIS 1, and 75 as mSIS 2. Besides, mSIS was significantly related to age and tumor size. On multivariate analysis, mSIS was identified as a predictor to independently predict OS (p < 0.001) along with RFS (p < 0.001), and a significantly strong correlation was observed at the advanced pTNM stages based on the mSIS system. In the subgroup analysis of adjuvant chemotherapy and surgery alone, mSIS was still the predictor for independently predicting patient OS (p < 0.001) together with RFS (p < 0.001) for the two groups. T-ROC analysis showed that mSIS was more accurate than controlling nutritional status score in predicting OS and RFS. Conclusions: The mSIS can serve as an easy, useful scoring system to independently predict the preoperative survival for AEJ cases undergoing surgery.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Yantao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| |
Collapse
|
|
40
|
Gao P, Cai N, Yang X, Yuan Z, Zhang T, Lu M, Jin L, Ye W, Suo C, Chen X. Association of Helicobacter pylori and gastric atrophy with adenocarcinoma of the esophagogastric junction in Taixing, China. Int J Cancer 2021; 150:243-252. [PMID: 34498732 DOI: 10.1002/ijc.33801] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/26/2021] [Accepted: 08/30/2021] [Indexed: 12/24/2022]
Abstract
Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ.
Collapse
Affiliation(s)
- Peipei Gao
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Ning Cai
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Xiaorong Yang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China
| | - Ziyu Yuan
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Department of Epidemiology and Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China
| | - Ming Lu
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China
| | - Li Jin
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Weimin Ye
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Chen Suo
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Department of Epidemiology and Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| |
Collapse
|
|
41
|
Chu LY, Zhou JY, Zhao YX, Ou YT, Yang T, Peng YH, Fang WK, Xu YW, Xie JJ. Serum CYR61 as a potential biomarker for the diagnosis of esophagogastric junction tumor. Biosci Rep 2021; 41:BSR20204117. [PMID: 34085702 PMCID: PMC8217984 DOI: 10.1042/bsr20204117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 04/10/2021] [Accepted: 04/23/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. The present study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. METHODS Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann-Whitney's U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. RESULTS Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05). CONCLUSION The present study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.
Collapse
Affiliation(s)
- Ling-Yu Chu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Jian-Yuan Zhou
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yi-Xuan Zhao
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yan-Ting Ou
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Tian Yang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Wang-Kai Fang
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| |
Collapse
|
|
42
|
Hu X, Wu L, Liu B, Chen K. Immune Infiltration Subtypes Characterization and Identification of Prognosis-Related lncRNAs in Adenocarcinoma of the Esophagogastric Junction. Front Immunol 2021; 12:651056. [PMID: 34122409 PMCID: PMC8195339 DOI: 10.3389/fimmu.2021.651056] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 05/14/2021] [Indexed: 12/12/2022] Open
Abstract
The incidence of adenocarcinoma of the esophagogastric junction (AEG) has markedly increased worldwide. However, the precise etiology of AEG is still unclear, and the therapeutic options thus remain limited. Growing evidence has implicated long non-coding RNAs (lncRNAs) in cancer immunomodulation. This study aimed to examine the tumor immune infiltration status and assess the prognostic value of immune-related lncRNAs in AEG. Using the ESTIMATE method and single-sample GSEA, we first evaluated the infiltration level of 28 immune cell types in AEG samples obtained from the TCGA dataset (N=201). Patients were assigned into high- and low-immune infiltration subtypes based on the immune cell infiltration’s enrichment score. GSEA and mutation pattern analysis revealed that these two immune infiltration subtypes had distinct phenotypes. We identified 1470 differentially expressed lncRNAs in two immune infiltration subtypes. From these differentially expressed lncRNAs, six prognosis-related lncRNAs were selected using the Cox regression analysis. Subsequently, an immune risk signature was constructed based on combining the values of the six prognosis-associated lncRNAs expression levels and multiple regression coefficients. To determine the risk model’s prognostic capability, we performed a series of survival analyses with Kaplan–Meier methods, Cox proportional hazards regression models, and the area under receiver operating characteristic (ROC) curve. The results indicated that the immune-related risk signature could be an independent prognostic factor with a significant predictive value in patients with AEG. Furthermore, the immune-related risk signature can effectively predict the response to immunotherapy and chemotherapy in AEG patients. In conclusion, the proposed immune-related lncRNA prognostic signature is reliable and has high survival predictive value for patients with AEG and is a promising potential biomarker for immunotherapy.
Collapse
Affiliation(s)
- Xin Hu
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Liuxing Wu
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Ben Liu
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Kexin Chen
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| |
Collapse
|
|
43
|
Chen J, Xia YJ, Liu TY, Lai YH, Yu JS, Zhang TH, Ooi S, He YL. Development and validation of a survival nomogram for patients with Siewert type II/III adenocarcinoma of the esophagogastric junction based on real-world data. BMC Cancer 2021; 21:532. [PMID: 33971833 PMCID: PMC8111941 DOI: 10.1186/s12885-021-08249-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 04/23/2021] [Indexed: 12/27/2022] Open
Abstract
Background The clinical staging systems for adenocarcinoma of the esophagogastric junction (AEG) are controversial. We aimed to propose a prognostic nomogram based on real-world data for predicting survival of Siewert type II/III AEG patients after surgery. Methods A total of 396 patients with Siewert type II/III AEG diagnosed and treated at the Center for Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-sen University, from June 2009 to June 2017 were enrolled. The original data of 29 variables were exported from the electronic medical records system. The nomogram was established based on multivariate Cox regression coefficients, and its performance was measured using Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curve analysis and calibration curve. Results A nomogram was constructed based on nine variables. The C-index for overall survival (OS) prediction was 0.76 (95% CI, 0.72 to 0.80) in the training cohort, in the validation-1 cohort was 0.79 (95% CI, 0.72 to 0.86), and 0.73 (95% CI, 0.67 to 0.80) in the validation-2 cohort. Time-dependent ROC curves and calibration curves in all three cohorts showed good prognostic predictive accuracy. We further proved the superiority of the nomogram in predictive accuracy for OS to pathological TNM (pTNM) staging system and other independent prognostic factors. Kaplan-Meier survival curves demonstrated the pTNM stage, grade of differentiation, positive lymph node, log odds of positive lymph node and organ invasion were prognostic factors with good discriminative ability. Conclusion The established nomogram demonstrated a more precise prognostic prediction for patients with Siewert type II/III AEG. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08249-x.
Collapse
Affiliation(s)
- Jian Chen
- Center for Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Yu-Jian Xia
- Center for Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Tian-Yu Liu
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yuan-Hui Lai
- Department of Thyroid and Breast Surgery, the Eastern Division of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ji-Shang Yu
- Center for Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Tian-Hao Zhang
- Center for Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Shiyin Ooi
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yu-Long He
- Center for Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China. .,Digestive Medicine Center, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.
| |
Collapse
|
|
44
|
Wang Y, Sun H, Zhu N, Wu X, Sui Z, Gong L, Yu Z. Myeloid-Derived Suppressor Cells in Immune Microenvironment Promote Progression of Esophagogastric Junction Adenocarcinoma. Front Oncol 2021; 11:640080. [PMID: 33854974 PMCID: PMC8039399 DOI: 10.3389/fonc.2021.640080] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 03/10/2021] [Indexed: 01/05/2023] Open
Abstract
Adenocarcinoma of the esophagogastric junction (AEG) is a fatal disease. Accumulating evidence indicates that, for a comprehensive understanding of AEG, studies should be conducted not only to investigate tumor cells, but also the tumor microenvironment (TME). In this study, we collected AEG patient data from The Cancer Genome Atlas, and used the CIBERSORT algorithm to analyze tumor-infiltrating immune cell profiles. The levels of CD8+ T cells and M0 and M2 macrophages were relatively high in AEG tissues. M2 macrophages were abundant in G3 tumors, and neutrophils were associated with poor prognosis. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immunosuppressive cells which share a similar origin to neutrophils and macrophages. We further analyzed the levels of MDSCs in AEG patients and healthy donors (HD) using flow cytometry. MDSC levels were elevated at tumor sites, with polymorphonuclear MDSCs (PMN-MDSCs) being the predominant subtype. Circulating MDSCs partly represented cells at the tumor site. We observed that PMN-MDSC levels at tumor sites were positively correlated with advanced staging, low grade, lymph node metastasis, and HER2− status. Immunohistochemistry and immunofluorescence analyses indicated that activation of the STAT3 and NF-κB pathways in MDSCs may be a potential mechanism for cancer progression. Our studies provided a comprehensive perspective involving tumor-infiltrating immune cells, and detailed insights into the proportion of MDSCs in AEG and their clinical significance. Together, these findings may improve our current understanding of cancer progression involving tumor-infiltrating immune cells in the TME.
Collapse
Affiliation(s)
- Ying Wang
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Haiyan Sun
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Ningning Zhu
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Xianxian Wu
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Zhilin Sui
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Lei Gong
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Zhentao Yu
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.,Department of Thoracic Surgery, Shenzhen Center, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen, China
| |
Collapse
|
|
45
|
Gossage JA. Minimally invasive left-sided esophagectomy (MILO): a novel approach for locally advanced tumors of the gastroesophageal junction. Dis Esophagus 2021; 34:5863450. [PMID: 32591785 DOI: 10.1093/dote/doaa059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/10/2020] [Accepted: 05/28/2020] [Indexed: 12/11/2022]
Abstract
Recent national audit has shown that levels of minimally invasive esophagectomy for cancer have increased to around 45% in the UK. The hybrid approach is the most common, with a laparoscopic abdominal phase and an open thoracic dissection. A number of centers have now adopted a two-phase Ivor-Lewis minimally invasive esophagectomy using a laparoscopic abdominal phase, followed by a thoracoscopic chest phase with a mini-thoracotomy to extract the specimen. The two-phase nature of the procedure lengthens the operative time and makes returning to the abdominal cavity difficult. The thoracotomy incision can also be painful and may reduce respiratory function post operatively. This report describes a novel single-phase minimally invasive left-sided technique with a mini-laparotomy for specimen extraction. This method offers excellent hiatal exposure, avoids a thoracotomy, and shortens the procedure time. Minimally invasive left-sided esophagectomy is a new useful approach for tumors located at the gastroesophageal junction.
Collapse
Affiliation(s)
- J A Gossage
- Guy's and St Thomas' Hospitals, London, UK.,King's College London, Faculty of Life Sciences & Medicine, London, UK
| |
Collapse
|
|
46
|
Tullio V, Gasperi V, Catani MV, Savini I. The Impact of Whole Grain Intake on Gastrointestinal Tumors: A Focus on Colorectal, Gastric, and Esophageal Cancers. Nutrients 2020; 13:E81. [PMID: 33383776 PMCID: PMC7824588 DOI: 10.3390/nu13010081] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/22/2020] [Accepted: 12/25/2020] [Indexed: 02/08/2023] Open
Abstract
Cereals are one of staple foods in human diet, mainly consumed as refined grains. Nonetheless, epidemiological data indicate that whole grain (WG) intake is inversely related to risk of type 2 diabetes, cardiovascular disease, and several cancer types, as well as to all-cause mortality. Particularly responsive to WG positive action is the gastrointestinal tract, daily exposed to bioactive food components. Herein, we shall provide an up-to-date overview on relationship between WG intake and prevention of gastrointestinal tumors, with a particular focus on colorectal, stomach, and esophagus cancers. Unlike refined counterparts, WG consumption is inversely associated with risk of these gastrointestinal cancers, most consistently with the risk of colorectal tumor. Some WG effects may be mediated by beneficial constituents (such as fiber and polyphenols) that are reduced/lost during milling process. Beside health-promoting action, WGs are still under-consumed in most countries; therefore, World Health Organization and other public/private stakeholders should cooperate to implement WG consumption in the whole population, in order to reach nutritionally effective intakes.
Collapse
|
|
47
|
Song D, Tian J, Hu Y, Wei Y, Lu H, Wang Y, Guan Q, Zhou Y. Identification of biomarkers associated with diagnosis and prognosis of gastroesophageal junction adenocarcinoma-a study based on integrated bioinformatics analysis in GEO and TCGA database. Medicine (Baltimore) 2020; 99:e23605. [PMID: 33371094 PMCID: PMC7748358 DOI: 10.1097/md.0000000000023605] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 11/09/2020] [Indexed: 12/19/2022] Open
Abstract
Gastroesophageal junction adenocarcinoma (GEJAC) is a malignant tumor with high mortality. Its incidence has increased sharply all over the world in recent years. The study aims to search for potential biomarkers for the diagnosis and prognosis of GEJAC based on the Gene Expression Omnibus database (GEO) database and The Cancer Genome Atlas (TCGA) database.Microarray dataset (GSE96668 and GSE74553) of GEJAC was downloaded from the GEO. After screening overlapping differentially expressed genes (DEGs) by GEO2R and Wayne map, functional enrichment analysis of the DEGs was performed by the DAVID database. Then, a protein-protein interaction (PPI) network was constructed, and the hub gene was identified by using STRING and Cytoscape, as well as the diagnostic value of hub genes was evaluated by the receiver operating characteristic (ROC) curves. Finally, the gene transcriptome profiles of gastric cancer named TCGA-STAD were downloaded from TCGA database to screen the potential prognostic genes and construct the prognostic risk model using Cox proportional hazards regression. Meanwhile, the Kaplan-Meier curve and time-dependent ROC curve were adopted to test the prognostic value of the prognostic gene signature.In this study, we identified 10 hub genes that might have high diagnostic value for GEJAC, and inferred that they might be involved in the occurrence and development of GEJAC. Moreover, we conducted a survival prediction model consisting of 6 genes and proved that they have value to some extent in predicting prognosis for GEJAC patients.
Collapse
Affiliation(s)
- Danlei Song
- The First Clinical Medical School of Lanzhou University
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province
| | - Jiming Tian
- The First Clinical Medical School of Lanzhou University
- Department of Obstetrics and Gynecology
| | - Yuping Hu
- The First Clinical Medical School of Lanzhou University
- Hospital of Reproductive Medicinal
| | - Yongjian Wei
- The First Clinical Medical School of Lanzhou University
- The Fifth Department of General Surgery
| | - Hong Lu
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province
| | - Yuping Wang
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province
| | - Quanlin Guan
- Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province
| |
Collapse
|
|
48
|
Xiong J, Wang Y, Kang W, Ma F, Liu H, Ma S, Li Y, Jin P, Hu H, Tian Y. Prognostic Importance of the Preoperative Naples Prognostic Score for Patients With Adenocarcinoma of the Esophagogastric Junction. Front Oncol 2020; 10:595793. [PMID: 33392090 PMCID: PMC7772432 DOI: 10.3389/fonc.2020.595793] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 11/09/2020] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The naples prognostic score (NPS) is established according to nutritional or inflammatory state, and it is identified as the new prognostic score for a variety of malignant tumors. However, its significance in cases suffering from adenocarcinoma of esophagogastric junction (AEJ) who receive surgery remains unclear so far. METHODS In this study, patients receiving surgery without preoperative therapy were examined between June 2007 and August 2017 in a retrospective way. Typically, the serum albumin level, total cholesterol level, neutrophil-to-lymphocyte ratio, together with the lymphocyte-to-monocyte ratio, was determined to calculate the NPS. The prognostic impact of NPS was evaluated using survival analyses. Time-dependent receiver operating characteristic curve (t-ROC) analysis was also carried out for comparing prognostic impacts of those scoring systems. RESULTS Altogether 231 cases were enrolled in this study. A higher NPS showed positive correlation with perineural invasion. Upon multivariate analysis, NPS was identified to be the independent prognostic factor to predict overall survival (OS) along with relapse-free survival (RFS) (both P< 0.05), and an especially strong correlation was observed at advanced pTNM stages based on NPS system. As for subgroup analyses on adjuvant chemotherapy or surgery only, NPS still independently predicted the OS as well as RFS (both P< 0.05) in both groups. Furthermore, t-ROC analysis showed that NPS was more accurate than the systemic inflammation score in predicting OS and RFS. CONCLUSIONS The NPS represents the simple and useful rating system, which can independently predict the survival for AEJ cases undergoing surgery.
Collapse
Affiliation(s)
- Jianping Xiong
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yaqin Wang
- Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Wenzhe Kang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fuhai Ma
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hao Liu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuai Ma
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peng Jin
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haitao 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, China
| | - Yantao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
49
|
Zhang X, Wang H, Han Y, Zhu M, Song Z, Zhan D, Jia J. NCAPG Induces Cell Proliferation in Cardia Adenocarcinoma via PI3K/AKT Signaling Pathway. Onco Targets Ther 2020; 13:11315-11326. [PMID: 33177839 PMCID: PMC7649252 DOI: 10.2147/ott.s276868] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/18/2020] [Indexed: 12/11/2022] Open
Abstract
Purpose Previous studies have shown that non-SMC condensin I complex subunit G (NCAPG) overexpression is correlated to poor prognosis of multiple cancer types. Herein, we explored the underlying mechanism of NCAPG-mediated cardia adenocarcinoma (CA) proliferation and cell cycle regulation. Methods The protein profiling technology was used to analyze the gene expression in 20 CA and adjacent tissue samples. Differential genes were identified by bioinformatic analysis. Western blot and qRT-PCR-based analysis assessed the NCAPG expression levels in multiple CA cell lines. CA cell lines, SGC-7901 and AGS, were transfected with Lip 2000, and stably transfected cell lines were screened for NCAPG overexpression and downregulation. MTT and clone formation assays were employed to detect cell proliferation, and cell cycle phases were analyzed using flow cytometry. Western blot was performed to determine the NCAPG gene expression levels. Finally, we studied the tumorigenic effects of NCAPG in the mouse model and validated the cell experiment results using immunohistochemistry. Results A significant overexpression of NCAPG was found in CA tissues and CA cell lines. The outcomes of MTT and clone formation assays showed that NCAPG upregulation promoted cell proliferation. The outcomes of these analyses were further validated using nude mice as an in vivo tumor model. As per the outcome of Western blot and flow cytometry analysis, NCAPG regulated the G1 phase through the cyclins (CDK4, CDK6, and cyclin D1) overexpression and cell cycle inhibitors (P21 and P27) downregulation. Overexpressed NCAPG and silenced NCAPG, both in vitro and in vivo, resulted in abnormal activation of the PI3K/AKT signaling pathway in CA cells. We observed that NCAPG overexpression increased the levels of phosphorylated PI3K, AKT, and GSK3β; however, their total protein levels remained unchanged in CA cells. Conclusion As a CA oncogene, NCAPG promoted cell proliferation and regulated cell cycle through PI3K/AKT signaling pathway activation.
Collapse
Affiliation(s)
- Xinxin Zhang
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China
| | - Hui Wang
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China
| | - Yajuan Han
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China
| | - Mengqi Zhu
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China
| | - Zaozhi Song
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China
| | - Dankai Zhan
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China
| | - Jianguang Jia
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China
| |
Collapse
|
|
50
|
Diaz LI, Mony S, Klapman J. Narrative review of the role of gastroenterologist in the diagnosis, treatment and palliation in gastric and gastroesophageal cancer. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1106. [PMID: 33145325 PMCID: PMC7575985 DOI: 10.21037/atm-20-4143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal cancer (EC) and gastric cancer (GC) carry a high mortality rate. Unfortunately, a majority of patients are asymptomatic and at the time of diagnosis, the disease may invariably be in its advanced stages with limited curative options. Thus, it is imperative to recognize certain risk factors including gastroesophageal reflux disease (GERD), male gender, pre-existing Barrett’s esophagus, smoking history, obesity, Helicobacter pylori infection, atrophic gastritis among others for both EC and GC, intervene on time with screening and surveillance modalities if indicated and optimize treatment plans. With advances in endoscopic techniques, early neoplastic lesions are increasingly managed by gastroenterologists, offering an alternative to surgery. The gold standard for diagnosis of EC and GC is high definition endoscopy with adequate targeted biopsies. Endoscopic ultrasound (EUS) is a key in the staging of early cancers dictating the pathway for treatment options. We also play a key role in palliation cases with the aim to reduce the symptoms like nausea, vomiting and even when possible, restore oral intake and improve nutrition in both advanced GC and EC. This review article discusses the risk factors, diagnostic and endoscopic treatment modalities of early EC and GC and palliation of advanced cancer where gastroenterologists play a key role.
Collapse
Affiliation(s)
- Liege I Diaz
- Department of Endoscopic Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Shruti Mony
- Division of Digestive Diseases and Nutrition, University of South Florida, Tampa, FL, USA
| | - Jason Klapman
- Department of Endoscopic Oncology, Moffitt Cancer Center, Tampa, FL, USA
| |
Collapse
|