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Zhou K, Li ZW, Wu Y, Wang ZJ, Wang LQ, Zhou LX, Jia L, Ji K, Yang XS, Zhang J, Wu XJ, Wang AQ, Bu ZD. Lymph node metastatic patterns of gastric carcinoma with a combination of adenocarcinoma and neuroendocrine carcinoma components. World J Gastroenterol 2025; 31:102347. [PMID: 40062330 PMCID: PMC11886515 DOI: 10.3748/wjg.v31.i8.102347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/14/2024] [Accepted: 01/07/2025] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma (G-MANEC) is a subtype of gastric cancer. Building upon prior research findings, we propose that tumours containing both neuroendocrine carcinoma (NEC) and adenocarcinoma (AC) components, with each component ranging from 1% to 99% of the tumour, be classified as a distinct entity. We hereby term this adenoneuroendocrine mixed gastric cancer (G-ANEC). Research on lymph node (LN) involvement in G-MANEC has focused mainly on metastasis status, with limited studies on metastatic composition. AIM To investigate the LN metastasis patterns of G-ANEC, the clinicopathological features associated with these metastasis patterns, and to explore adjuvant chemotherapy regimens for G-ANEC. METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022. Utilizing χ 2 tests in IBM statistical product and service solutions statistics and R software. RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion, tumour invasion depth, Lauren classification, and tumour location (P values: 0.008, 0.015, 0.01, and 0.004, respectively). When the SOX/XELOX regimen was applied for adjuvant chemotherapy, patients with LN metastasis comprising only AC exhibited better overall survival (OS) (94.25 ± 11.07 months vs 54.36 ± 11.36 months) than did those with NEC. When LN metastasis components contained NEC, there was a trend towards improved OS (64 ± 10.77 months vs 54.35 ± 11.36 months) and disease-free survival (71.28 ± 9.92 months vs 66.28 ± 11.93 months) in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen. CONCLUSION We found a significant correlation between the NEC percentage, tumour invasion depth, Lauren classification, and tumour location and LN metastasis patterns in G-ANEC. For G-ANEC, a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs. Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.
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Affiliation(s)
- Kai Zhou
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Zhong-Wu Li
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yan Wu
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Zhi-Jie Wang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ling-Qian Wang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Li-Xin Zhou
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ling Jia
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ke Ji
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xue-Song Yang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ji Zhang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiao-Jiang Wu
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - An-Qiang Wang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Zhao-De Bu
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
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Cheng Y, Du M, Wang Y, Li T, He C, Zhou X, Lin M, Huang Q. Risk Factors of Lymph Node Metastasis and Prognosis in 891 Chinese Patients With Submucosal Early Gastric Carcinoma, Emphasizing Differences Between Gastric Cardiac and Noncardiac Origins. Am J Surg Pathol 2024; 48:1293-1301. [PMID: 39028142 DOI: 10.1097/pas.0000000000002282] [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: 07/20/2024]
Abstract
Differences in risk factors (RF) of lymph node metastasis (LNM) and prognosis between submucosal early gastric cardiac (SEGCC) and noncardiac (SEGNCC) carcinomas remain unclear. In this study, we investigated and compared RF of LNM and prognosis in 891 patients with radical gastrectomy for SEGCC (n=217) or SEGNCC (n=674). Compared with SEGNCC, SEGCC displayed significantly higher proportion of elderly patients (70 y or above), the elevated macroscopic type, well/moderately differentiated tubular and low-grade papillary adenocarcinomas, as well as low-grade tumor budding, but lower prevalence of the depressed macroscopic type, poorly differentiated tubular adenocarcinoma, mixed adenocarcinoma, poorly cohesive carcinoma, lymphovascular invasion (LVI), perineural invasion, and high-grade tumor budding. By univariate analysis, significant RF for LNM of the cohort included female sex, poor differentiation, SM2 invasion, LVI, intermediate-grade and high-grade tumor budding, whereas tumor size, histology type, and perineural invasion were the significant RF for LNM in SEGNCC. By multivariate analysis, significant independent RF for LNM included female sex and LVI in SEGCC but were female sex, mixed adenocarcinoma, LVI, and high-grade tumor budding in SEGNCC. The 5-year overall survival was significantly worse in SEGCC than in SEGNCC for patients with LNM, but not for those without. For overall survival, LNM was the only significant independent RF in SEGCC, whereas age 70 years or above and LNM were independent RF in SEGNCC. The results of our study provided the clinicopathologic evidence for individualized clinical management strategies for these 2 groups of patients and suggested different pathogenesis mechanisms between SEGCC and SEGNCC.
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Affiliation(s)
| | - Mingzhan Du
- Department of Pathology of the First Affiliated Hospital of Soochow University, Suzhou
| | - Yaohui Wang
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine
| | - Ting Li
- Departments of Pathology
- Graduate School of Nanjing Medical University, Nanjing, China
| | - Chongfang He
- Departments of Pathology
- Graduate School of Nanjing Medical University, Nanjing, China
| | | | - Min Lin
- Departments of Pathology
- Department of Gastroenterology, Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, Changzhou
| | - Qin Huang
- Departments of Pathology
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
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Cheng YQ, Zhang XW, Zhuang SH, Zhou XL, Huang Q. Clinicopathological significance of intestinal metaplasia in endoscopically resected early gastric carcinoma. J Dig Dis 2023; 24:660-670. [PMID: 38100304 DOI: 10.1111/1751-2980.13245] [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: 08/05/2023] [Revised: 12/04/2023] [Accepted: 12/13/2023] [Indexed: 12/17/2023]
Abstract
OBJECTIVE To investigate the clinicopathological and prognostic significance of intestinal metaplasia (IM) in endoscopically resected early gastric carcinoma (EGC). METHODS Altogether 136 consecutive cases with EGC resected by endoscopic submucosal dissection over 5 years were included and divided into the early gastric cardiac (EGCC; n = 60) and non-cardiac carcinoma (EGNCC; n = 76) groups. Goblet cell IM and subtypes were determined with histology and immunostaining. Recurrence-free survival (RFS) was compared among various IM groups. RESULTS IM was identified in 128 (94.1%) EGC cases, including complete IM (n = 39), incomplete IM (n = 27), and mixed IM (n = 62). Incomplete IM was significantly more common in EGCC and exhibited a lower frequency of en bloc resection than the complete subtype. The frequency of synchronous or metachronous gastric tumor was significantly more common in EGCC with complete IM than in those with incomplete IM. Compared to EGC without IM, EGC with IM showed a significantly higher frequency of non-poorly cohesive carcinoma, en bloc resection, and non-eCuraC-1 grade. EGNCC with IM was significantly associated with negative resection margins and en bloc resection. The 5-year RFS was significantly lower in EGNCC patients with incomplete IM compared with those with mixed IM. The independent risk factors for RFS included tumor size >2 cm and eCuraC-1 grade. CONCLUSIONS Subtyping IM in EGC helped predict endoscopic resectability, prognosis, and risk of synchronous or metachronous gastric tumor. The significance of IM differed between EGCC and EGNCC. Large studies with longer follow-up are warranted to validate our findings.
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Affiliation(s)
- Yu Qing Cheng
- Department of Pathology, Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Xin Wen Zhang
- Department of Pathology, Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
- Graduate School of Dalian Medical University, Dalian, Liaoning Province, China
| | - Shao Hua Zhuang
- Department of Gastroenterology, Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Xiao Li Zhou
- Department of Pathology, Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Qin Huang
- Department of Pathology, Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
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Wu H, Liu W, Yin M, Liu L, Qu S, Xu W, Xu C. A nomogram based on platelet-to-lymphocyte ratio for predicting lymph node metastasis in patients with early gastric cancer. Front Oncol 2023; 13:1201499. [PMID: 37719022 PMCID: PMC10502215 DOI: 10.3389/fonc.2023.1201499] [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: 04/06/2023] [Accepted: 08/10/2023] [Indexed: 09/19/2023] Open
Abstract
Background Preoperative assessment of the presence of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) remains difficult. We aimed to develop a practical prediction model based on preoperative pathological data and inflammatory or nutrition-related indicators. Methods This study retrospectively analyzed the clinicopathological characteristics of 1,061 patients with EGC who were randomly divided into the training set and validation set at a ratio of 7:3. In the training set, we introduced the least absolute selection and shrinkage operator (LASSO) algorithm and multivariate logistic regression to identify independent risk factors and construct the nomogram. Both internal validation and external validation were performed by the area under the receiver operating characteristic curve (AUC), C-index, calibration curve, and decision curve analysis (DCA). Results LNM occurred in 162 of 1,061 patients, and the rate of LNM was 15.27%. In the training set, four variables proved to be independent risk factors (p < 0.05) and were incorporated into the final model, including depth of invasion, tumor size, degree of differentiation, and platelet-to-lymphocyte ratio (PLR). The AUC values were 0.775 and 0.792 for the training and validation groups, respectively. Both calibration curves showed great consistency in the predictive and actual values. The Hosmer-Lemeshow (H-L) test was carried out in two cohorts, showing excellent performance with p-value >0.05 (0.684422, 0.7403046). Decision curve analysis demonstrated a good clinical benefit in the respective set. Conclusion We established a preoperative nomogram including depth of invasion, tumor size, degree of differentiation, and PLR to predict LNM in EGC patients and achieved a good performance.
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Affiliation(s)
| | | | | | | | | | | | - Chunfang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Guo Q, Sun Q, Bian X, Wang M, Dong H, Yin H, Dai X, Fan G, Chen G. Development and validation of a multiphase CT radiomics nomogram for the preoperative prediction of lymphovascular invasion in patients with gastric cancer. Clin Radiol 2023; 78:e552-e559. [PMID: 37117048 DOI: 10.1016/j.crad.2023.03.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 03/13/2023] [Accepted: 03/22/2023] [Indexed: 04/30/2023]
Abstract
AIM To develop a nomogram to predict lymphovascular invasion (LVI) in gastric cancer by integrating multiphase computed tomography (CT) radiomics and clinical risk factors. MATERIALS AND METHODS One hundred and seventy-two gastric cancer patients (121 training and 51 validation) with preoperative contrast-enhanced CT images and clinicopathological data were collected retrospectively. The clinical risk factors were selected by univariate and multivariate regression analysis. Radiomic features were extracted and selected from the arterial phase (AP), venous phase (VP), and delayed phase (DP) CT images of each patient. Clinical risk factors, radiomic features, and integration of both were used to develop the clinical model, radiomic models, and nomogram, respectively. RESULTS Radiomic features from AP (n=6), VP (n=6), DP (n=7) CT images and three selected clinical risk factors were used for model development. The nomogram showed better performance than the AP, VP, DP, and clinical models in the training and validation datasets, providing areas under the curves (AUCs) of 0.890 (95% CI: 0.820-0.940) and 0.885 (95% CI:0.765-0.957), respectively. All models indicated good calibration, and decision curve analysis proved that the net benefit of the nomogram was superior to that of the clinical and radiomic models throughout the vast majority of the threshold probabilities. CONCLUSIONS The nomogram integrating multiphase CT radiomics and clinical risk factors showed favourable performance in predicting LVI of gastric cancer, which may benefit clinical practice.
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Affiliation(s)
- Q Guo
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - Q Sun
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - X Bian
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - M Wang
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - H Dong
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - H Yin
- Institute of Advanced Research, Beijing Infervision Technology Co., Ltd, Beijing, China
| | - X Dai
- Department of Pathology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - G Fan
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - G Chen
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China.
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Li R, Ma D, Zhang Q, Yang Y, Xing J, Nie D, Sun X, Li P, Zhang S. Comparison of endoscopic submucosal dissection outcomes between early gastric cardiac and non-cardiac cancers: a retrospective single-center study. Scand J Gastroenterol 2023; 58:1091-1100. [PMID: 37479679 DOI: 10.1080/00365521.2023.2233037] [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: 01/03/2023] [Revised: 05/23/2023] [Accepted: 06/30/2023] [Indexed: 07/23/2023]
Abstract
OBJECTIVES This study aims to compare the efficacy of endoscopic submucosal dissection (ESD) between early gastric cardiac cancer (EGCC) and early gastric non-cardiac cancer (EGNCC), and investigate associated risk factors for non-curative resection. METHODS Early gastric cancer (EGC) patients who underwent ESD from January 2015 to September 2020 in Beijing Friendship Hospital were consecutively enrolled. The clinical, histopathological and endoscopic data were retrospectively analyzed. The study was registered in Chinese Clinical Trial Registry (ChiCTR1800017117). RESULTS Among 500 patients with 534 EGC lesions, 117 patients with 118 lesions were allocated to the EGCC group, and 383 patients with 416 lesions to the EGNCC group. The rates of en bloc resection, complete resection and curative resection in the EGCC group were 97.5%, 78.8% and 71.2%, respectively, significantly lower than those in the EGNCC group (99.8%, 94.5% and 90.4%, p = .010, <.001 and <.001). Among non-curative resected lesions, EGCC had more cases in both endoscopic curability (eCura) C-1 and C-2 groups than EGNCC (10.2% and 18.6% vs. 2.4% and 7.2%, p < .001). Multivariate analysis showed that tumor size (OR 2.393, 95% CI 1.388-4.126) and submucosal invasion (OR 11.498, 95% CI 3.759-35.175) were risk factors for non-curative resection in the EGCC group. For EGCC larger than 3 cm, none achieved curative resection, 86.7% were classified as eCura C-2 and 46.7% exhibited deep submucosal infiltration. CONCLUSIONS The curative resection rate of ESD for EGCC was lower than that for EGNCC. ESD for EGCC larger than 3 cm should be cautiously considered.
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Affiliation(s)
- Rongxue Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Dan Ma
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Qian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Yi Yang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Jie Xing
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Dan Nie
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Xiujing Sun
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Faculty of Gastroenterology of Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
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GuoHui M, MingHua Z, ZhenYu C, JianHai L, ChunXi W, ZeLong Y. Comparable long-term outcomes after endoscopic therapy and gastrectomy of early adenocarcinoma of esophagogastric junction: a population-based study. Surg Endosc 2022; 36:7521-7528. [PMID: 35352149 DOI: 10.1007/s00464-022-09187-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 03/07/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND AIMS Current guidelines recommend consideration of endoscopic therapy (ET) when treating selected early gastric cancers. However, clinical decision-making on ET versus gastrectomy for early adenocarcinoma of esophagogastric junction (AEGJ) remains challenging because of uncertain long-term outcomes. METHODS We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results database from 2004 to 2017 of early AEGJ patients underwent ET or gastrectomy. Multivariate models were used to compare cancer-specific survival (CSS). RESULTS Of 881 included early AEGJ patients, 227 (36.2%) patients underwent ET and 654 (63.8%) patients underwent gastrectomy. Early AEGJ patients who underwent ET experienced a similar hazard of cancer-specific death compared with those underwent gastrectomy in both multivariate Cox regression (HR [hazard ratio], 0.93; 95% CI [confidence interval], 0.55-1.56; P = 0.78) and the multivariate competing risk model (subdistribution HR [SHR], 0.86; 95% CI 0.50-1.45; P = 0.56). Propensity score matching was used, 210 patients underwent ET were matched with 210 patients underwent gastrectomy. Patients underwent ET experienced a similar hazard of cancer-specific death compared with those underwent gastrectomy in both multivariate Cox regression (HR, 0.97; 95% CI 0.53-1.77; P = 0.92) and the multivariate competing risk model (SHR, 0.96; 95% CI 0.52-1.77; P = 0.89). CONCLUSION Early AEGJ patients who received ET or gastrectomy had comparable long-term outcomes, which lend support to the role of ET in the treatment of these patients.
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Affiliation(s)
- Mei GuoHui
- Senior Department of General Surgery & Department of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing, China.,Department of Urology, The Second People's Hospital of Fuyang City, Anhui, China
| | - Zhu MingHua
- Senior Department of General Surgery & Department of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Chang ZhenYu
- Senior Department of General Surgery & Department of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Long JianHai
- Pulmonary and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wang ChunXi
- Senior Department of General Surgery & Department of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing, China.,Senior Department of General Surgery, Hainan Hospital of PLA General Hospital, Hainan, China
| | - Yang ZeLong
- Senior Department of General Surgery & Department of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing, China. .,Senior Department of General Surgery, Hainan Hospital of PLA General Hospital, Hainan, China.
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8
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Zhao B, Zhu W. Exosomal miRNA-455 from Bone Marrow Stromal Cells (BMSCs) Promotes Macrophage Phagocytosis and Restrains Progression of Gastric Cancer (GC). J BIOMATER TISS ENG 2022. [DOI: 10.1166/jbt.2022.2939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Multiple miRNAs are differentially expressed in gastric cancer (GC). Herein, this study aims to investigate miR-455’s role in GC and its mechanism. Exosomes (exo) separated from BMSCs after transfection were co-cultured with either phagocytes, GC cells (NCI-N87 cell), or macrophages
combined with NCI-N87cells (mixed group) followed by analysis of the expression of PTEN, N-cadherin, E-cadherin, and PI3K, and AKT by RT-qPCR and Western blot. Increased miR-455 expression was observed in GC cells upon transfection. GC cells in the mixed group relative to NCI-N87 group exhibited
a lower cell migration and invasion and impaired proliferative capacity (p < 0.05), accompanied with higher expressions of N-cadherin, E-cadherin, PI3K, and AKT, and decreased level of PTEN (p < 0.05). The combined treatment resulted in a higher phagocytic rate (12.38±0.21%)
and phagocytic index (14.29±2.11%) compared to treatment with only phagocytes (p < 0.05). In conclusion, BMSC-derived exosomal miR-455 inhibits the growth of GC cells and promotes the phagocytosis through inactivating PI3K/AKT signaling pathway.
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Affiliation(s)
- Boxian Zhao
- Department of General Surgery, Huzhou Cent Hospital, Affiliated Cent Hospital Huzhou University, Huzhou, Zhejiang, 313003, China
| | - Weiguo Zhu
- Department of Anesthesia and Surgery, Huzhou Cent Hospital, Affiliated Cent Hospital Huzhou University, Huzhou, Zhejiang, 313003, China
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Wang N, Yang Y, Jia GZ, Wang K, Zhou S, Zhang B, Zhang ZS, Qiao Q, He XL. Long non-coding RNA Down syndrome cell adhesion molecule-anti-sense 1 promotes gastric carcinoma cell proliferation and migration by regulating the miR-204/TPT1 axis. Hum Exp Toxicol 2021; 40:S187-S195. [PMID: 34372727 DOI: 10.1177/09603271211036037] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Several recent studies have suggested that the long non-coding RNA (lncRNA) DSCAM-AS1 (Down syndrome cell adhesion molecule - anti-sense 1) is aberrantly expressed in many malignancies. Purpose: In this study, we aimed to explore the the role of DSCAM-AS1 in gastric carcinoma. Research Design: Expression of DSCAM-AS1 mRNA, miR-204, and TPT1 (Tumor Protein, Translationally-Controlled 1) were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of GC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between DSCAM-AS1, miR-204, and TPT1 were predicted and confirmed using a dual-luciferase reporter assay. Expression of TPT1 protein was quantified by Western blot. Results: In this study, we found that DSCAM-AS1 was significantly overexpressed in GC tissues and cell lines. Functional experiments indicated that GC cells with DSCAM-AS1 silencing exhibited a dynamic reduction in proliferation and migration. We identified miR-204 as a target of DSCAM-AS1 and found that it targeted TPT1 in GC cells, which further led to decreased expression of miR-204 in GC tissues and cell lines. A rescue assay revealed that knocked-down DSCAM-AS1 hindered GC progression, which was reversed upon miR-204 downregulation or TPT1 overexpression. Conclusion: We conclude that DSCAM-AS1 is expressed as a tumor oncogene in GC progression, modulated via the miR-204/TPT1 axis. These findings indicate the potential of DSCAM-AS1 as a therapeutic target for GC prevention.
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Affiliation(s)
- Nan Wang
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Ying Yang
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Guo-Zhan Jia
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Ke Wang
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Shuai Zhou
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Bo Zhang
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Zhan-Sheng Zhang
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Qing Qiao
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
| | - Xian-Li He
- Department of General Surgery, 56697Tangdu Hospital, The Air Force Medical University, Xi'an, China
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Zhong X, Xuan F, Qian Y, Pan J, Wang S, Chen W, Lin T, Zhu H, Wang X, Wang G. A genomic-clinicopathologic Nomogram for the preoperative prediction of lymph node metastasis in gastric cancer. BMC Cancer 2021; 21:455. [PMID: 33892676 PMCID: PMC8066490 DOI: 10.1186/s12885-021-08203-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 04/16/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Preoperative evaluation of lymph node (LN) state is of pivotal significance for informing therapeutic decisions in gastric cancer (GC) patients. However, there are no non-invasive methods that can be used to preoperatively identify such status. We aimed at developing a genomic biosignature based model to predict the possibility of LN metastasis in GC patients. METHODS We used the RNA profile retrieving strategy and performed RNA expression profiling in a large GC cohort (GSE62254, n = 300) from Gene Expression Ominus (GEO). In the exploratory stage, 300 GC patients from GSE62254 were involved and the differentially expressed RNAs (DERs) for LN-status were determined using the R software. GC samples in GSE62254 were randomly allocated into a learning set (n = 210) and a verification set (n = 90). By using the Least absolute shrinkage and selection operator (LASSO) regression approach, a set of 23-RNA signatures were established and the signature based nomogram was subsequently built for distinguishing LN condition. The diagnostic efficiency, as well as the clinical performance of this model were assessed using the decision curve analysis (DCA). Metascape was used for bioinformatic analysis of the DERs. RESULTS Based on the genomic signature, we established a nomogram that robustly distinguished LN status in the learning (AUC = 0.916, 95% CI 0.833-0.999) and verification sets (AUC = 0.775, 95% CI 0.647-0.903). DCA demonstrated the clinical value of this nomogram. Functional enrichment analysis of the DERs was performed using bioinformatics methods which revealed that these DERs were involved in several lymphangiogenesis-correlated cascades. CONCLUSIONS In this study, we present a genomic signature based nomogram that integrates the 23-RNA biosignature based scores and Lauren classification. This model can be utilized to estimate the probability of LN metastasis with good performance in GC. The functional analysis of the DERs reveals the prospective biogenesis of LN metastasis in GC.
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Affiliation(s)
- Xin Zhong
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China.
| | - Feichao Xuan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China
| | - Yun Qian
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China
| | - Junhai Pan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China
| | - Suihan Wang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China
| | - Wenchao Chen
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China
| | - Tianyu Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China
| | - Hepan Zhu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China
| | - Xianfa Wang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China.
| | - Guanyu Wang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, East Qingchun Road 3, Zhejiang, 310016, Hangzhou, China.
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11
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Clinical outcomes of early gastric cardiac cancer treated with endoscopic submucosal dissection in patients with different indications. BMC Gastroenterol 2021; 21:119. [PMID: 33711944 PMCID: PMC7953789 DOI: 10.1186/s12876-021-01700-0] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Endoscopic submucosal dissection (ESD) has been accepted as a standard treatment for early gastric cardiac cancer (EGCC). Here, we investigate the clinical outcomes of the EGCC patients who underwent ESD in different indications. METHODS From January 2011 to October 2019, we enrolled 502 EGCC lesions from 495 patients which were resected by ESD at our center. We retrospectively analyzed the short-term and long-term clinical outcomes among different indication groups. RESULTS The number of the patients in the absolute indication (AI), expanded indication (EI) and beyond the expanded indication (BEI) groups was 265, 137 and 93, respectively. The en bloc resection rate was 100%, 100% and 98.9% (P = 0.185). The complete resection rate was 99.3%, 98.5% and 74.5%, respectively (P < 0.001). During a median follow-up of 48.1 months, the lymph node metastasis rate was 0%, 0% and 2.3% (P < 0.001). The distant metastasis rate was 0.4%, 0% and 2.3% (P = 0.150). The five-year disease-specific survival rate in the BEI group was 96.6% (P = 0.016), compared to 99.6% in the AI group and 100% in the EI group. CONCLUSION The efficacy for ESD patients in EI group was almost equal to the AI group. Patients in the BEI group showed generally favorable clinical outcomes and needed to be carefully checked after ESD. ESD may be an optional treatment for patients unsuitable for gastrectomy.
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12
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Huang Q, Read M, Gold JS, Zou XP. Unraveling the identity of gastric cardiac cancer. J Dig Dis 2020; 21:674-686. [PMID: 32975049 DOI: 10.1111/1751-2980.12945] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 08/11/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022]
Abstract
The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.
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Affiliation(s)
- Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China.,Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Matthew Read
- Department of Surgery, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Jason S Gold
- Department of Surgery, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Xiao Ping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
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13
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Wang Y, Li X, Gao L, Wang C, Zhang Y, Huang Q. Distinct clinicopathological differences between early gastric cardiac and non-cardiac carcinomas: a single-center retrospective study of 329 radical resection cases. BMC Gastroenterol 2020; 20:351. [PMID: 33087057 PMCID: PMC7579997 DOI: 10.1186/s12876-020-01498-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 10/12/2020] [Indexed: 12/16/2022] Open
Abstract
Background Early gastric carcinoma is heterogeneous and can be divided into early gastric cardiac carcinoma (EGCC) and early gastric non-cardiac carcinoma (EGNCC) groups. At present, differences in clinicopathology remains obscure between EGCC and EGNCC fundus–corpus and antrum–angularis–pylorus subgroups, especially between EGCC with and without oesophageal invasion. Methods In this study, we studied 329 consecutive early gastric carcinoma radical gastrectomies with 70 EGCCs and 259 EGNCCs. Results Compared to the EGNCC antrum–angularis–pylorus (n = 181), but not fundus–corpus (n = 78), sub-group, EGCC showed significantly older age, lower prevalence of the grossly depressed pattern, better tumor differentiation, higher percentage of tubular/papillary adenocarcinoma, but lower frequency of mixed poorly cohesive carcinoma with tubular/papillary adenocarcinoma, and absence of lymph node metastasis (LNM) in tumors with invasion up to superficial submucosa (SM1). In contrast, pure poorly cohesive carcinoma was less frequently seen in EGCCs than in EGNCCs, but mixed poorly cohesive carcinoma with tubular/papillary adenocarcinomas was significantly more common in the EGNCC antrum–angularis–pylorus sub-group than in any other group. No significant differences were found between EGCC and EGNCC sub-groups in gender, tumor size, H. pylori infection rate, and lymphovascular/perineural invasion. EGCC with oesophageal invasion (n = 22), compared to EGCC without (n = 48), showed no significant differences in the H. pylori infection rate and oesophageal columnar, intestinal, or pancreatic metaplasia, except for a higher percentage of the former in size > 2 cm and tubular differentiation. Conclusions There exist distinct clinicopathologic differences between EGCC and EGNCC sub-groups; EGCC was indeed of gastric origin. Further investigations with larger samples are needed to validate these findings.
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Affiliation(s)
- Yaohui Wang
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiuqing Li
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lili Gao
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Chenxi Wang
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yifen Zhang
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
| | - Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China. .,Department of Pathology, Boston VA Healthcare System and Harvard Medical School, Boston, MA, USA.
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14
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Cao S, Zou T, Sun Q, Liu T, Fan T, Yin Q, Fan X, Jiang J, Raymond D, Wang Y, Zhang B, Lv Y, Zhang X, Ling T, Zhuge Y, Wang L, Zou X, Xu G, Huang Q. Safety and long-term outcomes of early gastric cardiac cancer treated with endoscopic submucosal dissection in 499 Chinese patients. Therap Adv Gastroenterol 2020; 13:1756284820966929. [PMID: 33193812 PMCID: PMC7594240 DOI: 10.1177/1756284820966929] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 09/24/2020] [Indexed: 02/04/2023] Open
Abstract
AIMS Early gastric cardiac cancer (EGCC) has a low risk of lymph node metastasis with the potential for endoscopic therapy. We aimed to evaluate the short- and long-term outcomes of endoscopic submucosal dissection (ESD)-resected EGCCs in a large cohort of Chinese patients and compare endoscopic and clinicopathologic features between EGCC and early gastric non-cardiac cancer (EGNC). METHODS We retrospectively studied 512 EGCCs in 499 consecutive patients and 621 EGNCs in 555 consecutive patients between January 2011 and March 2018 at our center. We investigated clinicopathological characteristics of EGCC tumors, ESD treatment results, adverse events, and postresection patient survival. RESULTS Compared with EGNC patients, EGCC patients were significantly older (average age: 66 years versus 62 years, p < 0.001). The percentage of the gross 0-IIc pattern was higher in EGCCs (46.1%) than in EGNCs (41.5%), while the frequency of the 0-IIa pattern was lower in EGCCs (14.9%) than in EGNCs (22.4%) (p = 0.001). Compared with EGNCs, EGCCs showed smaller size, deeper invasion, fewer ulcerated or poorly differentiated tumors, but more cases with gastritis cystica profunda. The prevalence of ESD-related complications was higher in EGCCs (6.1%) than in EGNCs (2.3%) (p = 0.001). In EGCCs, the disease-specific survival rate was significantly higher in patients of the noncurative resection group with surgery (100%), compared with that (93.9%) without surgery (p < 0.001). CONCLUSION Clinicopathological characteristics were significantly different between EGCCs and EGNCs. ESD is a safe and effective treatment option with favorable outcomes for patients with EGCC. Additional surgery improved survival in patients with noncurative ESD resection.
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Affiliation(s)
- Shouli Cao
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Tianhui Zou
- Division of Gastroenterology and Hepatology,
Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai
Institute of Digestive Disease; Key Laboratory of Gastroenterology and
Hepatology, Ministry of Health, Shanghai, China
| | - Qi Sun
- Department of Pathology, Affiliated Drum Tower
Hospital of Nanjing University Medical School, Nanjing, China
| | - Tianyun Liu
- Department of Pathology, Affiliated Drum Tower
Hospital of Nanjing University Medical School, Nanjing, China
| | - Ting Fan
- Department of Gastroenterology, Drum Tower
Clinical College of Nanjing Medical University, Nanjing, China
| | - Qin Yin
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiangshan Fan
- Department of Pathology, Affiliated Drum Tower
Hospital of Nanjing University Medical School, Nanjing, China
| | - Jingwei Jiang
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Dekusaah Raymond
- Department of Gastroenterology, Drum Tower
Clinical College of Nanjing Medical University, Nanjing, China
| | - Yi Wang
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Bin Zhang
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Ying Lv
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoqi Zhang
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Tingsheng Ling
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Lei Wang
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoping Zou
- Department of Gastroenterology, Affiliated Drum
Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Guifang Xu
- Department of Gastroenterology, The Affiliated
Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan
Road, Nanjing, Jiangsu 210008, China
- Department of Gastroenterology, Gaochun People
Hospital, Gaochun, China
| | - Qin Huang
- Department of Pathology, Affiliated Drum Tower
Hospital of Nanjing University Medical School, Nanjing, China
- VA Boston Healthcare System and Harvard Medical
School, West Roxbury, MA, USA
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15
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Tang X, Zhang M, He Q, Sun G, Wang C, Gao P, Qu H. Histological Differentiated/Undifferentiated Mixed Type Should Not Be Considered as a Non-Curative Factor of Endoscopic Resection for Patients With Early Gastric Cancer. Front Oncol 2020; 10:1743. [PMID: 33014861 PMCID: PMC7494733 DOI: 10.3389/fonc.2020.01743] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 08/04/2020] [Indexed: 12/13/2022] Open
Abstract
Background Histological differentiated/undifferentiated mixed-type adenocarcinomas are frequently found in patients with early gastric cancer (EGC). Yet it is unclear whether these mixed-type adenocarcinomas can be treated by endoscopic resection (ER) in EGC patients. Aims To evaluate the lymph node metastasis (LNM) rate and long-term outcomes in mixed-type EGC patients and assess the feasibility of ER in these patients. Methods Clinicopathological features, risk factors of LNM, and overall survival (OS) and progression-free survival (PFS) rates of EGC patients were analyzed according to different histological types. Results Patients with mixed-type EGC had higher LNM rates than patients with non-mixed-type EGC (11.4 vs. 6.2%, P = 0.044). In the multivariate analysis, larger tumor diameter, presence of an ulcer, submucosal invasion, histological undifferentiated type, histological mixed type, and lymphovascular invasion resulted as independent risk factors for LNM in EGC patients (all P < 0.05). The LNM rate in mixed-type patients who met the Japanese ER criteria was 3.3%, including fulfilling the absolute criteria 0%. The 5-year OS and PFS rates in mixed-type patients were 94.59 and 91.47%, respectively. There was no statistical significance in the OS (P = 0.870) and PFS (P = 0.705) between mixed-type and non-mixed-type EGC patients fulfilling the Japanese ER criteria. Conclusion Histological differentiated/undifferentiated mixed type in EGC patients meeting the Japanese absolute criteria for ER are associated with low risk of LNM and favorable prognosis, and thus, it should not be considered as a non-curative factor for ER.
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Affiliation(s)
- Xiaolong Tang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Mengjun Zhang
- Department of General Surgery, Lanling People's Hospital, Linyi, China
| | - Qingsi He
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Guorui Sun
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Chao Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Peng Gao
- Department of Pathology, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Qu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
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16
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Cheng Y, Zhou X, Xu K, Huang J, Huang Q. Very low risk of lymph node metastasis in Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma. BMC Gastroenterol 2020; 20:273. [PMID: 32807085 PMCID: PMC7433105 DOI: 10.1186/s12876-020-01422-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 08/11/2020] [Indexed: 02/06/2023] Open
Abstract
Background Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma (EBV-GCLS) is a rare variant of early gastric carcinomas. Clinicopathological features of this variant remain obscure, especially in Chinese patients. Therefore, we collected EBV-GCLS cases and studied clinicopathology and prognosis. Methods By a retrospective review of 595 consecutive radical gastrectomies for early gastric carcinoma from 2006 to 2018, we identified 8 (1.3%, 8/595) EBV-GCLS cases. Clinicopathologic characteristics were compared between EBV-GCLSs and 109 conventional early gastric carcinomas, which were divided into intramucosal, SM1, and SM2 subgroups. The latter 2 subgroups were classified according to the submucosal invasion depth below or over 500 μm. Results All 8 EBV-GCLSs occurred in male patients and invaded deep submucosa (SM2) without lymph node metastasis (LNM), four (50%) of which had synchronous non-gastric malignant tumors (3 gastric gastrointestinal stromal tumors and 1 primary clear cell renal cell carcinoma), and four (50%) arose in the proximal stomach. Compared to conventional early gastric carcinomas, EBV-GCLS was significantly more frequent with SM2 invasion, poor differentiation, and synchronous non-gastric carcinoma tumor, but not with age, gender, macroscopic type, location, size, perineural invasion, lymphovascular invasion, and pathologic stage. In invasion-depth stratified comparisons in the SM2 subgroup, the frequency of LNM in EBV-GCLS was significantly lower than that in conventional early gastric carcinomas (p < 0.05) and the 5-year survival rate of patients with EBV-GCLS was better than that with conventional early gastric carcinomas in 3 subgroups (100% vs 91.5, 85.7, 83.9%, respectively), although the differences did not reach a statistically significant level due to the small sample size. Significant differences among 4 subgroups were found in tumor grade, lymphovascular invasion, LNM, pathological stage, and synchronous tumor, but not in age, gender, macroscopic type, tumor size, location, perineural invasion. Conclusions Even with poor differentiation and SM2 invasion, EBV-GCLS showed very low risk of LNM and may be a candidate for endoscopic therapy such as endoscopic submucosal dissection.
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Affiliation(s)
- Yuqing Cheng
- Department of Pathology of the Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China
| | - Xiaoli Zhou
- Department of Pathology of the Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China
| | - Kequn Xu
- Department of Oncology of the Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China
| | - Jin Huang
- Department of Gastroenterology of the Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China
| | - Qin Huang
- Department of Pathology of the Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China. .,Department of Pathology and Laboratory Medicine of Veterans Affairs Boston Healthcare System, Harvard Medical School and Brigham and Women's Hospital, 1400 VFW Parkway, West Roxbury, MA, 02132, USA.
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17
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Huang Q, Shi J, Liu TY, Cheng YQ, Wang YH, Du MZ, Li L, Fan XS, Zhou XL, Zhang YF, Guo LC, Xu GF, Zou XP. Marked thickening of muscularis mucosae and submucosa in the gastric cardia: A histopathological study of 110 surgical resection cases. J Dig Dis 2020; 21:205-214. [PMID: 32223013 DOI: 10.1111/1751-2980.12860] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 03/12/2020] [Accepted: 03/25/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To investigate histopathologic changes of muscularis mucosae (MM) and submucosa in the gastric cardia. METHODS We performed a histopathology study of 50 distal esophagectomies with proximal gastrectomies for esophageal squamous cell carcinoma as the study (non-cancerous cardiac) group and 60 gastrectomies for early gastric cardiac carcinoma as the cancer group. The gastroesophageal junction was defined as the distal end of squamous epithelium, multilayered epithelium, or deep esophageal glands or ducts. Gastric cardia (n = 110) was defined as the presence of cardiac and cardio-oxyntic mucosae distal to the gastroesophageal junction. RESULTS The average thickness of MM and submucosa in the cardia was 1.04 and 1.41 mm, respectively, which was significantly thicker than that in distal stomach (n = 34) (0.22 and 0.99 mm) or distal esophagus (n = 92) (0.60 and 1.15 mm). In the cardia, thickened MM displayed frayed muscle fibers (93.3%) with a significantly higher prevalence of entrapped glands, cysts, and lymphoid follicles than in the distal stomach or distal esophagus. In the submucosa fatty changes, cysts, and abnormal arteries were significantly more common in the cardia than in the distal stomach or distal esophagus. Compared with the study group, the cardia in the cancer group showed significantly thicker MM (average 1.31 vs 0.72 mm) and submucosa (average 1.61 vs 1.16 mm), more frequent frayed MM (93.3% vs 60.0%), prolapse-like changes (50.0% vs 2.0%), and cysts (26.7% vs 4.0%). CONCLUSION MM and submucosa of the cardia were significantly thickened, especially in early gastric cardiac carcinomas.
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Affiliation(s)
- Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China.,Department of Pathology and Laboratory Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jiong Shi
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Tian Yun Liu
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Yu Qing Cheng
- Department of Pathology, Changzhou Second Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yao Hui Wang
- Department of Pathology, Jiangsu Provincial Hospital of Traditional Chinese Medicine Affiliated to Nanjing Medical University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Ming Zhan Du
- Department of Pathology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Lin Li
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Xiang Shan Fan
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Xiao Li Zhou
- Department of Pathology, Changzhou Second Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yi Fen Zhang
- Department of Pathology, Jiangsu Provincial Hospital of Traditional Chinese Medicine Affiliated to Nanjing Medical University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Ling Chuan Guo
- Department of Pathology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Gui Fang Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu Province, China
| | - Xiao Ping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu Province, China
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18
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Tumor Budding and Other Risk Factors of Lymph Node Metastasis in Submucosal Early Gastric Carcinoma: A Multicenter Clinicopathologic Study in 621 Radical Gastrectomies of Chinese Patients. Am J Surg Pathol 2020; 43:1074-1082. [PMID: 31094925 DOI: 10.1097/pas.0000000000001276] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Compared with early gastric intramucosal carcinoma, submucosal carcinoma is known to have a higher risk for lymph node metastasis (LMN), but risk factors in submucosal carcinoma remain elusive. In this multicenter study with 621 radical gastrectomies for submucosal early gastric carcinoma, we investigated tumor budding and other risk factors of LMN that were identified in 172 cases (27.7%). Overall, independent high-risk factors for LMN included lymphovascular invasion (odds ratio, 3.9; 95% confidence interval, 2.5-6.1), tumor budding (odds ratio, 3.3; 95% confidence interval, 1.9-5.9), mixed tubular/papillary adenocarcinoma with poorly cohesive carcinoma (odds ratio, 2.1; 95% confidence interval, 1.0-4.3), and female sex (odds ratio, 1.6; 95% confidence interval, 1.0-2.6), whereas gastric cardiac submucosal carcinomas had a significantly lower risk for LMN (odds ratio, 0.5; 95% confidence interval, 0.3-0.9). In 276 well/moderately differentiated tubular or papillary submucosal early gastric carcinomas, independent risk factors were tumor budding (odds ratio, 3.7; 95% confidence interval, 1.6-8.7), deep submucosal (SM2) invasion (odds ratio, 3.1; 95% confidence interval, 1.3-7.6), and lymphovascular invasion (odds ratio, 2.7; 95% confidence interval, 1.3-5.6). In 174 cases without tumor budding and lymphovascular invasion, no LMN was identified in 47 cardiac tumors, and 15 tumors <1.0 cm in size. In conclusion, tumor budding, lymphovascular invasion, mixed tubular/papillary adenocarcinoma with poorly cohesive carcinoma, and female gender were found to be significant high-risk factors for LMN in submucosal early gastric carcinoma, while submucosal gastric cardiac carcinoma had a significantly lower risk for nodal metastasis.
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Huang Q, Li R, Xu GF, Zhou D, Fan XS, Zou XP. Emerging evidence supports grouping by location of early gastric carcinoma for appropriate clinical management in Chinese patients. J Dig Dis 2018; 19:730-736. [PMID: 30270559 DOI: 10.1111/1751-2980.12674] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Revised: 09/12/2018] [Accepted: 09/21/2018] [Indexed: 12/11/2022]
Abstract
Gastric cancer is common in China. At present, early detection with prompt resection of early gastric carcinoma (EGC) is crucial for improving patient's survival. Because of high heterogeneity of EGC in Chinese patients we reviewed recent clinicopathological and molecular evidence and proposed a grouping EGC in three subgroups according to their location for appropriate management. In group 1 (cardia), most patients with EGC in this small location were elderly men. The tumors originated in the cardiac mucosa with a high proportion of cases with slightly elevated gross patterns and intestinal adenocarcinoma histology with moderate to well differentiation. Poorly cohesive carcinoma was infrequent. As the risk for lymph node metastasis in this kind of tumor was significantly lower than that in the distal stomach, endoscopic therapy is preferred. Group 2 (fundus-corpus), many patients with EGC in this large location were young women. The EGCs originated in the oxyntic mucosa with pure and mixed poorly cohesive carcinomas that are more commonly present in this area than in any other. Most tumors were poorly differentiated with a high risk for lymph node metastasis. Thus, endoscopic therapy may be appropriate for intramucosal, but not for submucosal, carcinoma. Group 3 (antrum-pylorus). EGC tumors arose from the antral mucosa, primarily because of Helicobacter pylori infection, following the Correa gastric cancer tumorigenetic pathway. Erosive and ulcerated gross patterns were most frequently observed. While most EGCs in this location were mainly intestinal adenocarcinomas, poorly differentiated EGCs were substantial in number. Because the risk of lymph node metastasis remains to be illustrated, clinical management requires an individualized approach. This preliminary observation requires verification in large nationwide multicenter studies.
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Affiliation(s)
- Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China.,Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Harvard Medical School and Brigham and Women's Hospital, West Roxbury, Massachusetts, USA
| | - Rui Li
- Department of Gastroenterology, The Affiliated First Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Gui Fang Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China
| | - Dan Zhou
- Quality Care Medical Consulting, LLC, Lexington, Massachusetts, USA
| | - Xiang Shan Fan
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China
| | - Xiao Ping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China
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