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Liu Z, Xia G, Liang X, Li S, Gong Y, Li B, Deng J. Construction and testing of a risk prediction classifier for cardia carcinoma. Carcinogenesis 2023; 44:662-670. [PMID: 37624090 DOI: 10.1093/carcin/bgad059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/19/2023] [Accepted: 08/21/2023] [Indexed: 08/26/2023] Open
Abstract
OBJECTIVES This research aimed to construct a prediction model for stages II and III cardia carcinoma (CC), and provide an effective preoperative evaluation tool for clinicians. METHODS CC mRNA expression matrix was obtained from Gene Expression Omnibus and The Cancer Genome Atlas databases. Non-negative matrix factorization was used to cluster data to obtain subgroup information, and weighted gene co-expression network analysis was used to uncover key modules linked to different subgroups. Gene-set enrichment analysis analyzed biological pathways of different subgroups. The related pathways of multiple modules were scrutinized with Kyoto Encyclopedia of Genes and Genomes. Key modules were manually annotated to screen CC-related genes. Subsequently, quantitative real-time polymerase chain reaction assessed CC-related gene expression in fresh tissues and paraffin samples, and Pearson correlation analysis was performed. A classification model was constructed and the predictive ability was evaluated by the receiver operating characteristic curve. RESULTS CC patients had four subgroups that were associated with brown, turquoise, red, and black modules, respectively. The CC-related modules were mainly associated with abnormal cell metabolism and inflammatory immune pathways. Then, 76 CC-elated genes were identified. Pearson correlation analysis presented that THBS4, COL14A1, DPYSL3, FGF7, and SVIL levels were relatively stable in fresh and paraffin tissues. The area under the curve of 5-gene combined prediction for staging was 0.8571, indicating good prediction ability. CONCLUSIONS The staging classifier for CC based on THBS4, COL14A1, DPYSL3, FGF7, and SVIL has a good predictive effect, which may provide effective guidance for whether CC patients need emergency surgery.
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Affiliation(s)
- Zhiqiang Liu
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
- Department of Gastric Surgery, Anyang Tumor Hospital, Anyang City 455000, P.R. China
- Tianjin Medical University, Tianjin 300070, P.R. China
| | - Ganshu Xia
- Department of Gastric Surgery, Anyang Tumor Hospital, Anyang City 455000, P.R. China
| | - Xiaolong Liang
- Department of Gastric Surgery, Anyang Tumor Hospital, Anyang City 455000, P.R. China
| | - Shoumiao Li
- Department of Gastric Surgery, Anyang Tumor Hospital, Anyang City 455000, P.R. China
| | - Yanxin Gong
- Department of Gastric Surgery, Anyang Tumor Hospital, Anyang City 455000, P.R. China
| | - Baozhong Li
- Department of Gastric Surgery, Anyang Tumor Hospital, Anyang City 455000, P.R. China
| | - Jingyu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
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Çapkinoğlu E, Tufan AE, Ömeroğlu S, Tanal M, Güven O, Demir U. Positive lymph node ratio as a prognostic factor for gastric cancer patients: Is it going to supersede positive lymph node number in guidelines? Medicine (Baltimore) 2023; 102:e33757. [PMID: 37335735 DOI: 10.1097/md.0000000000033757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023] Open
Abstract
Gastric malignancies constitute the sixth most common cancer with regards to incidence and have the fifth most mortality rates. Extended lymph-node dissection is the surgical modality of choice while treating advanced stage gastric cancer. It is yet a topic of debate, whether or not the amount of positive lymph nodes after a pathological examination following the surgical intervention is of prognostic value. In this study, it is aimed to evaluate the prognostic significance of positive lymph nodes following the surgery. A total of 193 patients who underwent curative gastrectomy between January 2011 and December 2015 have been considered for a retrospective data collection. The cases with R1-R2 resections, palliative or emergent surgeries are excluded. Metastatic to total number of lymph nodes, corresponded a ratio which was analyzed in this survey and practiced as a predictive parameter of disease outcome. This survey includes 138 male (71.5%) and 55 female (28.5%) patients treated between 2011 and 2015 in our clinic. The survey follow-up duration of the cases range between 0, 2, and 72 months, corresponding an average of 23.24 ± 16.99 months. We calculated cutoff value of 0.09 with, sensitivity is 76.32% for positive to total number of lymph nodes ratio, whereas specivity applies for 64.10%, positive predictive value for 58% and negative predictive value for 80.6%. Positive lymph node ratio has a prognostic value in terms of predicting the prognosis of the patients with gastric adenocarcinoma following a curative gastrectomy. This might in long term contribute to the prognostic analysis of patients if integrated in the current staging system.
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Affiliation(s)
- Emir Çapkinoğlu
- Department of General Surgery, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Istanbul, Turkey
| | - Aydin Eray Tufan
- Department of General Surgery, Sisli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey
| | - Sinan Ömeroğlu
- Department of General Surgery, Sisli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey
| | - Mert Tanal
- Department of General Surgery, Tekirdag Ismail Fehmi Cumalioglu MD City Hospital, Tekirdag, Turkey
| | - Onur Güven
- Department of General Surgery, Sisli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey
| | - Uygar Demir
- Department of General Surgery, Sisli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey
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Huang Y, Huang Y, Wang H, Zhang H, Shi L, Li C, Li X, Zeng Y, Liu Y, Wu M, Wang J, Wang J. The effect of low molecular weight-polycyclic aromatic hydrocarbons responsive hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 circuit on inflammatory response of A549 cells via the PI3K/AKT pathway and epithelial-mesenchymal transition process. ENVIRONMENTAL TOXICOLOGY 2022; 37:2005-2018. [PMID: 35475590 DOI: 10.1002/tox.23546] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 04/07/2022] [Accepted: 04/10/2022] [Indexed: 06/14/2023]
Abstract
Inflammation is widely recognized as an essential inducer of epithelial-mesenchymal transition (EMT). Meanwhile, competitive endogenous RNA (ceRNA) has been involved in a variety of disease processes. Therefore, the aim of the current study is to explore the regulation of ceRNA in the PI3K/AKT pathway and EMT mechanism in inflammatory response caused by low molecular weight-polycyclic aromatic hydrocarbons (LMW-PAHs). The A549 cells were treated with an equal mixture of phenanthrene (Phe) and fluorene (Flu), and total RNA was extracted for transcriptome sequencing. The target regulation of ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 was further determined for mechanism study. The mixture of Phe and Flu significantly upregulated the expressions of hsa_circ_0039929 and FGF2, down-regulated hsa-miR-15b-3p_R-1, activated the PI3K/AKT pathway and promoted EMT. Mechanically, the overexpression of hsa-miR-15b-3p_R-1 inhibited the expressions of hsa_circ_0039929 and FGF2, reversed the activation of PI3K/AKT signaling pathway by LMW-PAHs, and blocked the occurrence of EMT progression. Furthermore, knockdown of hsa_circ_0039929 could promote the levels of hsa-miR-15b-3p_R-1, while inhibit the expression of FGF2. The effects of hsa_circ_0039929 knockdowns on PI3K/AKT pathways and EMT progress resembled the hsa-miR-15b-3p_R-1 overexpression. All above suggested that ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 played an important role in the inflammation and EMT caused by LMW-PAHs.
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Affiliation(s)
- Yushan Huang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Yamin Huang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Huiling Wang
- Department of Integrated Chinese and Western Medicine Gynecology, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, China
| | - Haojun Zhang
- Department of Hospital Infection Control, Gansu Province Hospital, Lanzhou, China
| | - Lei Shi
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Chengyun Li
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Xiangli Li
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Yong Zeng
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Yang Liu
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Minghua Wu
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
| | - Jingyu Wang
- Department of Pathophysiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Junling Wang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
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Three-year outcomes of the randomized phase III SEIPLUS trial of extensive intraoperative peritoneal lavage for locally advanced gastric cancer. Nat Commun 2021; 12:6598. [PMID: 34782599 PMCID: PMC8594430 DOI: 10.1038/s41467-021-26778-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 10/05/2021] [Indexed: 12/17/2022] Open
Abstract
Whether extensive intraoperative peritoneal lavage (EIPL) after gastrectomy is beneficial to patients with locally advanced gastric cancer (AGC) is not clear. This phase 3, multicenter, parallel-group, prospective randomized study (NCT02745509) recruits patients between April 2016 and November 2017. Eligible patients who had been histologically proven AGC with T3/4NxM0 stage are randomly assigned (1:1) to either surgery alone or surgery plus EIPL. The results of the two groups are analyzed in the intent-to-treat population. A total of 662 patients with AGC (329 patients in the surgery alone group, and 333 in the surgery plus EIPL group) are included in the study. The primary endpoint is 3-year overall survival (OS). The secondary endpoints include 3-year disease free survival (DFS), 3-year peritoneal recurrence-free survival (reported in this manuscript) and 30-day postoperative complication and mortality (previously reported). The trial meets pre-specified endpoints. Estimated 3-year OS rates are 68.5% in the surgery alone group and 70.6% in the surgery plus EIPL group (log-rank p = 0.77). 3-year DFS rates are 61.2% in the surgery alone group and 66.0% in the surgery plus EIPL group (log-rank p = 0.24). The pattern of disease recurrence is similar in the two groups. In conclusion, EIPL does not improve the 3-year survival rate in AGC patients.
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Han C, Xu T, Zhang Q, Liu J, Ding Z, Hou X. The New American Joint Committee on Cancer T staging system for stomach: increased complexity without clear improvement in predictive accuracy for endoscopic ultrasound. BMC Gastroenterol 2021; 21:255. [PMID: 34116629 PMCID: PMC8196466 DOI: 10.1186/s12876-020-01558-8] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022] Open
Abstract
Background The efficacy of endoscopic ultrasound (EUS) for determining the T category of gastric cancer is variable. The aim of this study was to evaluate the superiority of EUS by using the 6th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the new 7th/8th edition. Methods A retrospective analysis of clinical and EUS imaging features of 348 gastric carcinoma patients who underwent radical resection were retrospectively analyzed. Differences between the 6th and 7th/8th edition T staging systems for preoperative EUS evaluation were compared. Results The accuracy of EUS T staging was 72.4% for the 7th/8th edition and 78.4% for the 6th edition. T3 stage accuracy was significantly worse when the T3 group status was changed. The tumor location, echoendoscope type, and histological type were associated with inaccuracy. We further analyzed the EUS image features for each tumor T stage and found that an indistinctly visible muscularis propria (MP) or with obvious thickening was considered an indicator of lesions involved in the MP with a sensitivity of 81.3%; an MP completely disappeared and accompanied with a serosal layer intact may be a marker that the lesion invaded to the subserosa. We also found that irregularities in the outer edge of the gastric wall were markers of gastric serosal layer penetration with a positive predictive value of 92.2%. Conclusions The increased complexity of the 7th/8th edition T staging system is accompanied by worsening of the predictive accuracy for EUS as compared to the 6th edition. Furthermore, the tumor location, echoendoscope type, histological type, and EUS image features for each tumor T stage should warrant attention.
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Affiliation(s)
- Chaoqun Han
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Xu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qin Zhang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jun Liu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhen Ding
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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Extensive peritoneal lavage with saline after curative gastrectomy for gastric cancer (EXPEL): a multicentre randomised controlled trial. Lancet Gastroenterol Hepatol 2020; 6:120-127. [PMID: 33253659 DOI: 10.1016/s2468-1253(20)30315-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 09/18/2020] [Accepted: 09/22/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Peritoneal recurrence of gastric cancer after curative surgical resection is common and portends a poor prognosis. Early studies suggest that extensive intraoperative peritoneal lavage (EIPL) might reduce the risk of peritoneal recurrence and improve survival. We aimed to evaluate the survival benefit of EIPL in patients with gastric cancer undergoing curative gastrectomy. METHODS In this open-label, phase 3, multicentre randomised trial, patients aged 21-80 years with cT3 or cT4 gastric cancer undergoing curative resection were enrolled at 22 centres from South Korea, China, Japan, Malaysia, Hong Kong, and Singapore. Patients were randomly assigned to receive surgery and EIPL (EIPL group) or surgery alone (standard surgery group) via a web-based programme in random permuted blocks in varying block sizes of four and six, assuming equal allocation between treatment groups. Randomisation was stratified according to study site and the sequence was generated using a computer program and concealed until the interventions were assigned. After surgery in the EIPL group, peritoneal lavage was done with 1 L of warm (42°C) normal 0·9% saline followed by complete aspiration; this procedure was repeated ten times. The primary endpoint was overall survival. All analyses were done assuming intention to treat. This trial is registered with ClinicalTrials.gov, NCT02140034. FINDINGS Between Sept 16, 2012, and Aug 3, 2018, 800 patients were randomly assigned to the EIPL group (n=398) or the standard surgery group (n=402). Two patients in the EIPL group and one in the standard surgery group withdrew from the trial immediately after randomisation and were excluded from the intention-to-treat analysis. At the third interim analysis on Aug 28, 2019, the predictive probability of overall survival being significantly higher in the EIPL group was less than 0·5%; therefore, the trial was terminated on the basis of futility. With a median follow-up of 2·4 years (IQR 1·5-3·0), the two groups were similar in terms of overall survival (hazard ratio 1·09 [95% CI 0·78-1·52; p=0·62). 3-year overall survival was 77·0% (95% CI 71·4-81·6) for the EIPL group and 76·7% (71·0-81·5) for the standard surgery group. 60 adverse events were reported in the EIPL group and 41 were reported in the standard surgery group. The most common adverse events included anastomotic leak (ten [3%] of 346 patients in the EIPL group vs six [2%] of 362 patients in the standard surgery group), bleeding (six [2%] vs six [2%]), intra-abdominal abscess (four [1%] vs five [1%]), superficial wound infection (seven [2%] vs one [<1%]), and abnormal liver function (six [2%] vs one [<1%]). Ten of the reported adverse events (eight in the EIPL group and two in the standard surgery group) resulted in death. INTERPRETATION EIPL and surgery did not have a survival benefit compared with surgery alone and is not recommended for patients undergoing curative gastrectomy for gastric cancer. FUNDING National Medical Research Council, Singapore.
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Liu J, Xu H, Wang N, Sun M. miR-15b, a diagnostic biomarker and therapeutic target, inhibits oesophageal cancer progression by regulating the PI3K/AKT signalling pathway. Exp Ther Med 2020; 20:222. [PMID: 33363587 DOI: 10.3892/etm.2020.9352] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 05/29/2020] [Indexed: 12/12/2022] Open
Abstract
MicroRNA (miR)-15b is an important regulator in several types of cancer, such as gastric cancer, colorectal cancer and oesophageal squamous cell carcinoma. The PI3K/AKT signalling pathway has been implicated in the growth and metastasis of oesophageal cancer (EC). The aim of the present study was to investigate the biological effects of miR-15b in EC, as well as the underlying mechanism involving the PI3K/AKT signalling pathway. The present study included 74 patients with EC and 74 healthy volunteers. The expression of miR-15b in peripheral blood mononuclear cells (PBMCs) and EC cell lines was evaluated via reverse transcription-quantitative PCR. The receiver operating characteristic curve was plotted to determine the diagnostic significance of miR-15b. EC cell viability, apoptosis, migration and invasion were analysed by conducting MTT, flow cytometry and transwell assays, respectively. Protein expression levels were analysed via western blotting. The results indicated that PBMCs isolated from patients with EC had lower miR-15b expression levels compared with PBMCs isolated from healthy volunteers. In patients with EC, miR-15b expression was strongly associated with tumour size, lymph node metastasis, TNM stage, fibrous membrane invasion and histologic grade. The results of the gain/loss-of-function in vitro experiments indicated that miR-15b inhibited EC cell viability, migration and invasion, facilitated EC cell apoptosis and attenuated the PI3K/AKT signalling pathway in EC109 and TE10 cells. Treatment of EC cells with the PI3K/AKT pathway agonist recilisib displayed the opposite effects, blocking the inhibitory function of miR-15b mimic on EC cell viability, migration and invasion. In summary, the results indicated that miR-15b suppressed EC cell viability, migration and invasion, and promoted EC cell apoptosis by inhibiting the PI3K/AKT signalling pathway.
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Affiliation(s)
- Jie Liu
- Department of Thoracic Surgery, Shandong Institute of Tumor Control, Shandong Cancer Hospital, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong 250000, P.R. China
| | - Haiyan Xu
- The Second Department of Operating Room, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China
| | - Nan Wang
- Laboratory Department, Affiliated Hospital of Weifang Medical College, Weifang, Shandong 261031, P.R. China
| | - Mingyan Sun
- Laboratory Department, Affiliated Hospital of Weifang Medical College, Weifang, Shandong 261031, P.R. China
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Prognostic factors for survival in patients with gastric cancer: Single-centre experience. North Clin Istanb 2020; 7:146-152. [PMID: 32259036 PMCID: PMC7117626 DOI: 10.14744/nci.2019.73549] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 09/05/2019] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE: We aimed to investigate survival outcomes and survival-related prognostic factors in gastric cancer patients who were followed-up or received adjuvant therapy in our center. METHODS: Patients with gastric cancer treated between 2005 and 2016 were evaluated retrospectively. We included 345 non-metastatic (stage I-III) gastric cancer patients in the study. The clinical, demographic, histologic data of the patients and treatment characteristics were obtained from the patient’s files. RESULTS: While 50 patients were stage I, 94 patients were stage II, 201 patients were stage III. While 221 patients (64%) presenting with serosal or adjacent visceral organ invasion or with involved lymph nodes were treated with adjuvant chemoradiotherapy, 124 patients presenting with early-stage disease were followed after surgery. Median follow up time was 34 months (4–156 months). While the median overall survival (OS) was 51 months, median disease-free survival (DFS) was 35 months. Overall survival and disease-free survival rates for 1st, 3rd and 5th years were 85%, 55%, 45% and 72%, 49%, 38%, respectively. According to univariate analysis, tumor size, T stage (p<0.001), N stage (p<0.001), TNM stage (p<0.001), grade (p<0.001) and presence of lymphovascular invasion (p=0.005) were determined as prognostic factors that affect overall survival significantly. According to the multivariate analysis, only T and N stage (p<0.001) were determined as independent prognostic factors for overall survival. CONCLUSION: Many different prognostic factors have been defined for gastric cancer. In concordance with the literature, we found T and N stages as prognostic factors in univariate and multivariate analysis.
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Tang X, He Q, Sun G, Qu H, Liu J, Gao L, Shi J, Ye J, Liang Y. Total Tumor Volume Should be Considered as an Important Prognostic Factor for Synchronous Multiple Gastric Cancer Patients with Curative Gastrectomy. Pathol Oncol Res 2020; 26:2169-2175. [PMID: 32170582 DOI: 10.1007/s12253-020-00804-4] [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: 04/29/2019] [Accepted: 03/04/2020] [Indexed: 11/30/2022]
Abstract
Synchronous multiple gastric cancer (SMGC) was a special type of gastric cancer with relatively low incidence. This article was designed to demonstrate that the total tumor volume (TTV) should be treated as an important prognostic factor in SMGC patients with curative gastrectomy. This study retrospective analyzed 140 SMGC patients who received curative gastrectomy between December 2004 and December 2014 in our hospital. Clinicopathological features, preoperative evaluation, surgical treatment, and outcome parameters were reviewed and analyzed. This study applied univariate and multivariate analyses to identify the most significant prognostic factors. In the univariate analysis, the TTV, pTTVNM, pN stage, pT of main tumor were all significant prognostic factors in SMGC patients (all P < 0.05). In the multivariate analysis, pN stage, TTV and pTTVNM were confirmed to be independent prognostic factors (all P < 0.05). In the comparison of survival analysis, the pTTVNM stage system (P < 0.05) was superior to the pTNM stage system (P > 0.05) in SMGC patients. In conclusion, the TTV should be considered as an independent prognostic factor in overall survival in SMGC patients who received curative gastrectomy. The pTTVNM stage should be recommended as a suitable staging system for SMGC patients.
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Affiliation(s)
- Xiaolong Tang
- Department of General Surgery, Qilu Hospital of Shandong University, No.107, West of Wenhua Street, Lixia District, 250012, Jinan, China
| | - Qingsi He
- Department of General Surgery, Qilu Hospital of Shandong University, No.107, West of Wenhua Street, Lixia District, 250012, Jinan, China
| | - Guorui Sun
- Department of General Surgery, Qilu Hospital of Shandong University, No.107, West of Wenhua Street, Lixia District, 250012, Jinan, China.
| | - Hui Qu
- Department of General Surgery, Qilu Hospital of Shandong University, No.107, West of Wenhua Street, Lixia District, 250012, Jinan, China
| | - Jia Liu
- Department of Health Management Center, Qilu Hospital of Shandong University, 250012, Jinan, China
| | - Lei Gao
- Qilu Medical College of Shandong University, 250011, Jinan, Shandong, China
| | - Jingbo Shi
- Qilu Medical College of Shandong University, 250011, Jinan, Shandong, China
| | - Jianhong Ye
- Qilu Medical College of Shandong University, 250011, Jinan, Shandong, China
| | - Yahang Liang
- Qilu Medical College of Shandong University, 250011, Jinan, Shandong, China
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Abstract
BACKGROUND AND AIM The present multicenter, retrospective study aimed at determining the factors affecting survival in patients who were operated on due to gastric cancer (GC). PATIENTS AND METHODS The data of 234 patients, who underwent elective surgery due to GC were retrospectively analyzed. The demographic characteristics, tumor localization and diameter, type of resection and lymph node dissection, experience of the operating surgeon (senior or junior), tumor grade, pT stage, number of lymph nodes harvested, number of lymph nodes with and without metastasis, tumor stage and survival data were recorded. RESULTS Survival was better a tumor diameter <4 cm, lower localization, experience of the operating surgeon (senior), without metastatic lymph nodes, tumor grade and decreased invasion depth (p < .05). There was no statistically significant difference between D1 LND and D2 LND with respect to survival (p = .793). Mortality was higher and survival was lower in patients with metastatic lymph nodes (p = .001). A number of harvested lymph nodes of 16 or more increased mortality (p = .003). Also, as disease stage increased, there was a decrease in survival and increase in mortality rates (p = .001). CONCLUSIONS Survival outcomes in resectable GCs are affected by the experience of the surgeon and patient-related factors at the time of surgery, including tumor size, T stage, and presence of metastatic lymph nodes.
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Affiliation(s)
- Suleyman Orman
- Department of General Surgery, Göztepe Teaching and Research Hospital, University of İstanbul Medeniyet, İstanbul, Turkey
| | - Haci Murat Cayci
- Department of General Surgery, Bursa Yuksek Ihtisas Teaching and Research Hospital, University of Medical Sciences, Bursa, Turkey
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Mahar AL, Zagorski B, Kagedan D, Dixon M, El-Sedfy A, Vasilevska-Ristovska J, Cortinovis D, Rowsell C, Law C, Helyer L, Paszat L, Coburn N. Evaluating TNM stage prognostic ability in a population-based cohort of gastric adenocarcinoma patients in a low-incidence country. Canadian Journal of Public Health 2018; 109:480-488. [PMID: 30091108 DOI: 10.17269/s41997-018-0102-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 06/19/2018] [Indexed: 12/20/2022]
Abstract
OBJECTIVES TNM stage is the preeminent cancer staging system and a fundamental determinant of disease prognosis. Our goal was to evaluate the predictive power of TNM stage for gastric adenocarcinoma (GAC), in a low-incidence country. METHODS A province-wide chart review of GAC patients diagnosed from April 1, 2005 to March 31, 2008 was conducted in Ontario and linked to routinely collected vital status data with a follow-up on March 31, 2012. TNM staging was classified using the sixth and seventh Union International for Cancer Control/American Joint Committee on Cancer editions. Kaplan-Meier and log-rank tests compared stage-stratified survival estimates. Discrimination was evaluated using Harrell's C statistic. RESULTS The cohort included 2366 patients. One- and 5-year survival was 43% and 17%. Using the sixth edition, 9% of patients had stage I disease, 5.4% stage II, 7.3% stage III, and 64% stage IV; 15% were not staged. Using the seventh edition, 9% were stage I, 7.7% stage II, 16% stage III, and 54% stage IV; 14% were not staged. Stage-stratified 5-year survival ranged from 68% to 7% with the sixth edition and from 70% to 4% with the seventh edition. Harrell's C statistic was 0.64 (0.63-0.65) for the broad sixth edition staging categories and 0.68 (0.67-0.69) for the broad seventh edition. Discriminative power was similar for the refined stage categories and across multiple subgroup analyses; it was best in non-metastatic patients. CONCLUSION Existing staging systems for GAC used in North America predict individualized prognosis poorly. The creation of a more complex prediction tool is necessary to provide accurate and precise prognostication information to oncologists, patients, and their families.
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Affiliation(s)
- Alyson L Mahar
- Manitoba Centre for Health Policy, Department of Community Health Sciences, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. .,Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. .,Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
| | - Brandon Zagorski
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada
| | - Daniel Kagedan
- Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Matthew Dixon
- Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Abraham El-Sedfy
- Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
| | | | | | | | - Calvin Law
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, ON, Canada.,Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Lucy Helyer
- Department of Surgery, Dalhousie University, Halifax, NS, Canada
| | - Lawrence Paszat
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.,Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Natalie Coburn
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, ON, Canada.,Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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12
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Kim G, Chen E, Tay AY, Lee JS, Phua JN, Shabbir A, So JB, Tai BC. Extensive peritoneal lavage after curative gastrectomy for gastric cancer (EXPEL): study protocol of an international multicentre randomised controlled trial. Jpn J Clin Oncol 2017; 47:179-184. [PMID: 28173154 DOI: 10.1093/jjco/hyw153] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Revised: 09/15/2016] [Accepted: 11/21/2016] [Indexed: 12/27/2022] Open
Abstract
Peritoneal recurrence after gastrectomy for gastric cancer is common and the prognosis is dismal. Recent evidence suggests that extensive peritoneal lavage with large volume of normal saline after surgery before abdominal closure can reduce the risk of peritoneal recurrence and improve overall survival. This study aims to evaluate the benefit of extensive intraoperative peritoneal lavage. This is a prospective, open-label, multicentre randomised controlled trial involving 15 international centres in China, Korea, Japan, Malaysia and Singapore. Patients with cT3/4 stomach cancer undergoing curative resection are randomised to either extensive peritoneal lavage (10 l of saline) or standard lavage (≤2 l of saline). The primary outcome is overall survival and secondary outcomes include disease-free survival and peritoneal recurrence. The minimum sample size is 600 subjects with 300 per arm completing 3 years follow-up. The data will be analysed on an intention-to-treat basis, assuming a two-sided test with a 5% level of significance.
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Affiliation(s)
- Guowei Kim
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Elya Chen
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Amy Yl Tay
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Jin San Lee
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Janelle Ns Phua
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Asim Shabbir
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Jimmy By So
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Bee Choo Tai
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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13
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Lei G, Yang H, Hong T, Zhou C, Li J, Liu W, Hu J, Zeng L, Chen G, Chen Q, Zhang Y, Yang N. Elastic staining-a rejuvenated method to reassess prognosis and serosal invasion in patients with pT3N0M0 gastric cancer. Hum Pathol 2017; 65:79-84. [PMID: 28504204 DOI: 10.1016/j.humpath.2017.04.023] [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: 02/16/2017] [Revised: 04/12/2017] [Accepted: 04/29/2017] [Indexed: 10/19/2022]
Abstract
Prognosis of pT3N0M0 gastric cancer (GC) varies greatly, though the major factor conferring poor prognosis is unclear. Subserosal elastic lamina invasion (ELI+) is closely associated with poor outcomes in pT3 colorectal cancer, but related research on GC is unavailable. This study aimed to identify the influence of ELI+ on the prognosis of patients with pT3N0M0 GC and its relationship with serosal invasion using elastic staining. We retrospectively reviewed 94 and 28 patients with pT3N0M0 and pT4aN0M0 GC who underwent gastrectomy between 1994 and 2005. For the former, one section with invasion depth closest to the peritoneal surface and one corresponding paraffin block for each specimen were selected for conventional elastic staining to assess the relationship between ELI+ and patients' clinical characteristics and survival. pT3N0M0 GC specimens were divided into 3 groups based on staining results: ELI+ (N=51), non-invasion (N=31), and unidentified (N=12). ELI+ was closely related to recurrence and lymphovascular invasion. Five-year disease-free (DFS) (46%) and overall (OS) (36%) survival rates were significantly lower in the ELI+ than in the non-invasion or unidentified groups (P<.0001); no obvious difference was found between the ELI+ and pT4aN0M0 groups (P=.25). Multivariate analysis showed ELI+ and recurrence as independent prognostic factors for DFS in pT3 GC patients. In conclusion, elastic staining is an effective and highly feasible method for predicting prognosis and evaluating the serosal invasion depth of pT3 GC. pT3 GC accompanied with ELI+ is an obvious adverse prognostic factor and could be considered a treatment for pT4a GC.
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Affiliation(s)
- Guang Lei
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013; Graduate School, University of South China, Hunan Hengyang, China, 421001
| | - Haiyan Yang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013
| | - Ting Hong
- Graduate School, University of South China, Hunan Hengyang, China, 421001
| | - Chunhua Zhou
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013
| | - Jigang Li
- Department of Pathology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013
| | - Wenbin Liu
- Department of Pathology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013
| | - Jun Hu
- Department of Pathology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013
| | - Liang Zeng
- Department of Pathology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013
| | - Gong Chen
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013; Graduate School, University of South China, Hunan Hengyang, China, 421001
| | - Qiong Chen
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013; Graduate School, University of South China, Hunan Hengyang, China, 421001
| | - Yongchang Zhang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013.
| | - Nong Yang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 410013.
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14
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Liu S, Zheng H, Zhang Y, Chen L, Guan W, Guan Y, Ge Y, He J, Zhou Z. Whole-volume apparent diffusion coefficient-based entropy parameters for assessment of gastric cancer aggressiveness. J Magn Reson Imaging 2017; 47:168-175. [PMID: 28471511 DOI: 10.1002/jmri.25752] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 04/13/2017] [Indexed: 12/19/2022] Open
Abstract
PURPOSE To explore the role of whole-volume apparent diffusion coefficient (ADC)-based entropy parameters in the preoperative assessment of gastric cancer's aggressiveness. MATERIALS AND METHODS In all, 64 patients with gastric cancers who underwent 3.0T magnetic resonance imaging (MRI) were retrospectively included. Regions of interest were drawn manually using in-house software, around gastric cancer lesions on each slice of the diffusion-weighted images and ADC maps. Entropy-related parameters based on ADC maps were calculated automatically: (1) first-order entropy; (2-5) second-order entropies, including entropy(H)0 , entropy(H)45 , entropy(H)90 , and entropy(H)135 ; (6) entropy(H)mean ; and (7) entropy(H)range . Correlations between entropy-related parameters and pathological characteristics were analyzed with the Spearman correlation test. The parameters were compared among different pathological characteristics with independent-samples Kruskal-Wallis or Mann-Whitney U-test. Additionally, diagnostic performances of parameters in differentiating different pathological characteristics were analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS All the entropy-related parameters significantly correlated with T, N, and overall stages, especially the first-order entropy (r = 0.588, 0.585, and 0.677, respectively, all P < 0.05). All the entropy-related parameters showed significant differences in gastric cancers at different T, N, and overall stages, as well as at different status of vascular invasion (P < 0.001-0.027). And four parameters, including entropy, entropy(H)0 , entropy(H)45 , and entropy(H)90 , showed significant differences between gastric cancers with and without perineural invasion (P 0.006-0.040). CONCLUSION Entropy-related parameters derived from whole-volume ADC texture analysis could help assess the aggressiveness of gastric cancers via analyzing intratumoral heterogeneity quantitatively, especially the first-order entropy. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:168-175.
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Affiliation(s)
- Song Liu
- Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, P.R. China
| | - Huanhuan Zheng
- Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, P.R. China
| | - Yujuan Zhang
- Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, P.R. China
| | - Ling Chen
- Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, P.R. China
| | - Wenxian Guan
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, P.R. China
| | - Yue Guan
- School of Electronic Science and Engineering, Nanjing University, Nanjing, P.R. China
| | - Yun Ge
- School of Electronic Science and Engineering, Nanjing University, Nanjing, P.R. China
| | - Jian He
- Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, P.R. China
| | - Zhengyang Zhou
- Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, P.R. China
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15
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Huang T, Wang L, Liu D, Li P, Xiong H, Zhuang L, Sun L, Yuan X, Qiu H. FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1. Int J Oncol 2017; 50:1501-1512. [PMID: 28339036 PMCID: PMC5403236 DOI: 10.3892/ijo.2017.3927] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 03/03/2017] [Indexed: 02/07/2023] Open
Abstract
Fibroblast growth factor 7 (FGF7) is a mesenchyme-specific heparin-binding growth factor that binds FGF receptor 2 (FGFR2) to regulate numerous cellular and physiological processes. FGF7/FGFR2 signal is associated with gastric cancer progression. In the present study, we investigated the molecular mechanism by which FGF7/FGFR2 promotes invasion and migration in human gastric cancer. We first demonstrated that increased FGFR2 expression in human gastric cancer tissues was significantly associated with tumor depth and clinical stage in human gastric cancer tissues. Thrombospondin 1 (THBS1) is an extracellular glycoprotein that plays multiple roles in cell-matrix and cell-cell interactions. Increased expression of THBS1 significantly correlated with tumor differentiation. FGFR2 and THBS1 expression were both increased in cancer tissues as compared with adjacent normal tissues and their expression was positively correlated. In vitro, FGF7 stimulation of cell invasion and migration was partially suppressed by the FGFR2 knockdown. In addition, FGF7/FGFR2 upregulated THBS1, and cell invasion and migration were decreased by knockdown of THBS1. Furthermore, the PI3K/Akt/mTOR signaling pathway was predominantly responsible for FGF7/FGFR2-induced THBS1 upregulation. Taken together, our data suggest that FGF7/FGFR2/THBS1 is associated with the regulation of invasion and migration in human gastric cancer.
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Affiliation(s)
- Tingting Huang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Lei Wang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Dian Liu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Piao Li
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Huihua Xiong
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Liang Zhuang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Li Sun
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Xianglin Yuan
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Hong Qiu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
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16
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Oh SJ, Suh BJ, Park JK, Oh SD, Yu HJ. Prognostic Discrepancy of the 6th and 7th UICC N Classification for Lymph Node Staging in Gastric Cancer Patients after Curative Resection. Case Rep Oncol 2017; 10:57-65. [PMID: 28203165 PMCID: PMC5301159 DOI: 10.1159/000455189] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 12/19/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The validity of N classification of the 7th edition of the American Joint Committee on Cancer/Union Internationale contre le Cancer (AJCC/UICC) tumor-node-metastasis (TNM) staging system is still under debate. The purpose of this study was to evaluate the prognostic efficacy of the 7th edition of the AJCC/UICC TNM staging system (focusing on N stage), in comparison with the 6th edition, at a single Eastern institution. METHODS We analyzed 1,435 patients with gastric cancer who underwent curative resection performed from September 1998 to August 2003 at the Memorial Jin-Pok Kim Korea Gastric Cancer Center. We analyzed the survival rate of the patients according to the AJCC/UICC 6th and 7th editions, and compared each stage, focusing on N stage. RESULTS Significant differences in the 5-year survival rates were observed between the 6th and the 7th AJCC/UICC staging system. In the 6th edition staging system, the Kaplan-Meier curves discriminated each N stage significantly. In contrast, there was no difference in terms of survival curves for N stage according to the 7th edition, especially between N1 and N2: the Kaplan-Meier plots of survival curves between N1 (77.0%) and N2 (78.1%) stages overlapped significantly (p < 0.05). CONCLUSION Although the 7th UICC staging system is a more detailed and sophisticated system in the T category, there was no prognostic significance between the pN1 and pN2 stages according to our data. Therefore, we suggest establishing a new UICC staging system taking into consideration the application of the N stage.
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Affiliation(s)
- Sung Jin Oh
- Department of Surgery, Haeundae Paik Hospital, Busan, Republic of Korea; Memorial Jin-Pok Kim Korea Gastric Cancer Center, Inje University College of Medicine, Busan, Republic of Korea
| | - Byoung Jo Suh
- Department of Surgery, Haeundae Paik Hospital, Busan, Republic of Korea; Memorial Jin-Pok Kim Korea Gastric Cancer Center, Inje University College of Medicine, Busan, Republic of Korea
| | - Jong Kwon Park
- Department of Surgery, Haeundae Paik Hospital, Busan, Republic of Korea
| | - Sung Don Oh
- Department of Surgery, Haeundae Paik Hospital, Busan, Republic of Korea
| | - Hang Jong Yu
- Department of Surgery, Korea Cancer Center Hospital, Seoul, Republic of Korea
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17
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Liu HT, Wang YW, Xing AY, Shi DB, Zhang H, Guo XY, Xu J, Gao P. Prognostic Value of microRNA Signature in Patients with Gastric Cancers. Sci Rep 2017; 7:42806. [PMID: 28202938 PMCID: PMC5311868 DOI: 10.1038/srep42806] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 01/13/2017] [Indexed: 01/28/2023] Open
Abstract
The occurrence of lymph node metastases (LNM) after endoscopic submucosal dissection (ESD) in patients with gastric cancer (GC) leads to poor prognosis. However, few biomarkers are available to predict LNM in GC patients. Thus, we measured expression of 6 cancer-related miRNAs using real-time RT-PCR in 102 GC samples that were randomized into a training set and a testing set (each, 51 cases). Using logistic regression, we identified 4-miRNA (miR-27b, miR-128, miR-100 and miR-214) signatures for predicting LNM in GC patients. Patients with high-risk scores for the 4-miRNA signature tended to have higher LNM than those with low-risk scores. Meanwhile, the ROC curve of the 4-miRNA signature was better for predicting LNM in GC patients. In addition, Cox regression analysis indicated that a 2-miRNA signature (miR-27b and miR-214) or a miR-214/N stage signature was predictive of survival for GC patients. This work describes a previously unrecognized 4-miRNA signature involved in LNM and a 2-miRNA signature or miR-214/N stage signature related to GC patients’ survival.
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Affiliation(s)
- Hai-Ting Liu
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Ya-Wen Wang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Ai-Yan Xing
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Duan-Bo Shi
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Hui- Zhang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Xiang-Yu Guo
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Jing- Xu
- Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China.,Department of Pathology, Qingdao Central Hospital, Qingdao, P.R. China
| | - Peng Gao
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
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18
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Kwon OK, Kim SW, Chae HD, Ryu SW, Chung HY, Kim SW, Lee WK, Yu W. Validation of the 7th AJCC/UICC staging system for gastric cancer and a proposal for a new TNM system based on a prognostic score: a retrospective multicenter study. Ann Surg Treat Res 2016; 91:295-302. [PMID: 27904851 PMCID: PMC5128375 DOI: 10.4174/astr.2016.91.6.295] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 07/31/2016] [Accepted: 08/03/2016] [Indexed: 01/29/2023] Open
Abstract
Purpose We validate the 7th American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system for gastric cancer and propose a new staging system that reflects the prognostic significances of each of T and N category. Methods Data from 5,957 patients who underwent curative gastrectomies from 2000 to 2007 at 4 university hospitals in Daegu Metropolitan city in Korea were analyzed for the validation of the 7th AJCC/UICC staging system for gastric cancer. The hazard ratios of the respective T and N categories were estimated and converted to weightings and summated to make prognostic score (P-score). Homogeneity and stage grouping were determined according to the P-scores. Results In the 7th AJCC/UICC staging system for gastric cancer, poor discrimination was noted between stages IIB and IIIA (P = 0.152). In addition, heterogeneity in stage IIB (P = 0.021) and a small gap in 5-year survival rates (1.7%) between stages IA and IB were noted. A new proposed staging system was generated on the basis of P-scores and demonstrated more discrimination between stages and more homogeneity within stages. The new staging system reflects the different prognostic impacts of N3a and N3b. Conclusion Several controversial issues of the 7th AJCC/UICC staging system for gastric cancer were reconfirmed in the present analysis. The TNM system based on P-score appears to be more scientifically accurate than the 7th AJCC/UICC staging system for gastric cancer.
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Affiliation(s)
- Oh Kyoung Kwon
- Department of Surgery, Kyungpook National University School of Medicine, Daegu, Korea
| | - Se Won Kim
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Hyun-Dong Chae
- Department of Surgery, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Seung Wan Ryu
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Ho Young Chung
- Department of Surgery, Kyungpook National University School of Medicine, Daegu, Korea
| | - Sang Woon Kim
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Won Kee Lee
- Biomedical Research Institute, Kyungpook National University School of Medicine, Daegu, Korea
| | - Wansik Yu
- Department of Surgery, Kyungpook National University School of Medicine, Daegu, Korea
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19
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de Mestier L, Lardière-Deguelte S, Volet J, Kianmanesh R, Bouché O. Recent insights in the therapeutic management of patients with gastric cancer. Dig Liver Dis 2016; 48:984-94. [PMID: 27156069 DOI: 10.1016/j.dld.2016.04.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Revised: 04/14/2016] [Accepted: 04/14/2016] [Indexed: 01/19/2023]
Abstract
Gastric cancer remains frequent and one of the most lethal malignancies worldwide. In this article, we aimed to comprehensively review recent insights in the therapeutic management of gastric cancer, with focus on the surgical and perioperative management of resectable forms, and the latest advances regarding advanced diseases. Surgical improvements comprise the use of laparoscopic surgery including staging laparoscopy, a better definition of nodal dissection, and the development of hyperthermic intraperitoneal chemotherapy. The best individualized perioperative management should be assessed before curative-intent surgery for all patients and can consists in perioperative chemotherapy, adjuvant chemo-radiation therapy or adjuvant chemotherapy alone. The optimal timing and sequence of chemotherapy and radiation therapy with respect to surgery should be further explored. Patients with advanced gastric cancer have a poor prognosis. Nevertheless, they can benefit from doublet or triplet chemotherapy combination, including trastuzumab in HER2-positive patients. Upon progression, second-line therapy can be considered in patients with good performance status. Although anti-HER2 (trastuzumab) and anti-VEGFR (ramucirumab) may yield survival benefit, anti-EGFR and anti-HGFR therapies have failed to improve outcomes. Nevertheless, combination regimens containing cytotoxic drugs and targeted therapies should be further evaluated; keeping in mind that gastric cancer biology is different between Asia and the Western countries.
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Affiliation(s)
- Louis de Mestier
- Service d'Hépato-Gastroentérologie et de Cancérologie Digestive, CHU Robert Debré, Reims, France
| | | | - Julien Volet
- Service d'Hépato-Gastroentérologie et de Cancérologie Digestive, CHU Robert Debré, Reims, France; Unité de Médecine Ambulatoire - Cancérologie-Hématologie, CHU Robert Debré, Reims, France
| | - Reza Kianmanesh
- Service de Chirurgie Générale, Digestive et Endocrinienne, CHU Robert Debré, Reims, France
| | - Olivier Bouché
- Service d'Hépato-Gastroentérologie et de Cancérologie Digestive, CHU Robert Debré, Reims, France; Unité de Médecine Ambulatoire - Cancérologie-Hématologie, CHU Robert Debré, Reims, France.
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20
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Gastric Cancer: Preoperative TNM Staging With Individually Adjusted Computed Tomography Scanning Phase. J Comput Assist Tomogr 2016; 40:160-6. [PMID: 26720202 DOI: 10.1097/rct.0000000000000339] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate test bolus scan technology on preoperative diagnostic performance, vascular enhancement, and artery visualization for gastric cancer. METHODS The institutional review board approved this study. Fifty-four patients in protocol 1 were resigned to a fixed delay time scan method, and their images were obtained in the late arterial phase (AP) and portal venous phase (PP), with start delays of 40 and 70 seconds, respectively. Fifty-six patients in protocol 2 had undergone the test bolus method first and received the time to peak enhancement of the aorta. Their images were obtained in the AP and PP with start delays in the time to peak enhancement and 20 seconds after the AP, respectively. Two radiologists performed consensus interpretation of the preoperative TNM staging, vascular enhancement, tumor contrast-to-noise ratio (CNR) and artery visualization between the 2 protocols. RESULTS There is no significant difference in the T, N, and M staging diagnostic accuracy between the protocols (P = 0.41, P > 0.99, and P = 0.34, respectively). For serosa-negative (T1, T2, and T3) tumors, the diagnostic accuracy obtained with protocol 2 was superior to that obtained with protocol 1 (P = 0.04). Protocol 2 was superior for perigastric vessel enhancement (left gastric artery, right gastroepiploic artery, and splenic artery; P < 0.001, P < 0.001, and P = 0.001, respectively). The stomach-to-tumor CNR during the PP of protocol 2 was significantly higher than that during either the AP or PP of protocol 1 (P = 0.004 and P = 0.001, respectively). The mean rankings of the artery visualization were significantly higher with protocol 2 than with protocol 1 (P < 0.001). CONCLUSIONS The dual-phase scan with test bolus technology could improve the tumor CNR and had high staging accuracy for serosa-negative tumors as well as high perigastric artery enhancement, yielding satisfactory artery visualization for diagnosis.
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Imamura T, Komatsu S, Ichikawa D, Kosuga T, Okamoto K, Konishi H, Shiozaki A, Fujiwara H, Otsuji E. Clinical characteristics of hepatoduodenal lymph node metastasis in gastric cancer. World J Gastroenterol 2015; 21:10866-73. [PMID: 26478677 PMCID: PMC4600587 DOI: 10.3748/wjg.v21.i38.10866] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2015] [Revised: 07/01/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the clinical features of hepatoduodenal lymph node (HDLN) metastasis and to clarify the optimal indication of HDLN dissection. METHODS We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy, including HDLN dissection, for gastric cancer between 1999 and 2012. Of these, 26 patients (9.4%) had HDLN metastasis. First, we investigated the clinicopathological characteristics, their perioperative clinical outcomes, such as postoperative complications, and prognostic outcomes between patients with and without HDLN metastasis. Second, we detected the prognostic factors, particularly in patients with HDLN metastasis. Third, we assessed the therapeutic value of HDLN dissection to determine its optimal indication. RESULTS The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location (the middle or lower stomach [P = 0.005, OR = 5.88 (95%CI: 1.61-38.1)] and pT category [T3 or T4, P = 0.017, OR = 4.45 (95%CI: 1.28-21.3)] were independent risk factors for HDLN metastasis. Cox proportional hazard analysis identified pN3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021, HR = 5.17 (95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection, HDLN metastasis was a prognostic indicator in pN3 gastric cancer (P < 0.0001), but not pN1-2 (P = 0.602). Furthermore, the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0, respectively. CONCLUSION We suggest that HDLN dissection should be indicated for pN1 or pN2 gastric cancers located at the middle or lower stomach.
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Go SI, Lee MJ, Lee WS, Choi HJ, Lee US, Kim RB, Kang MH, Kim HG, Lee GW, Kang JH, Lee JH, Kim SJ. D-Dimer Can Serve as a Prognostic and Predictive Biomarker for Metastatic Gastric Cancer Treated by Chemotherapy. Medicine (Baltimore) 2015; 94:e951. [PMID: 26222870 PMCID: PMC4554111 DOI: 10.1097/md.0000000000000951] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Systemic activation of hemostasis and thrombosis has been implicated in tumor progression and metastasis. D-dimer has been used as an indicator for the thrombosis. Here, we investigated the role of the activation of coagulation in patients with metastatic gastric cancer by measuring D-dimer level.We conducted an observation study of 46 metastatic gastric cancer patients who received palliative chemotherapy (CTx). D-dimer levels were assessed before CTx and at the first response evaluation after CTx.The overall survival (OS) of patients with pretreatment D-dimer levels <1.5 μg/mL was significantly longer than that of patients with D-dimer levels ≥1.5 μg/mL (22.0 vs 7.9 months, P = 0.019). At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11 μg/mL in patients either with partial response or stable disease (P = 0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46 μg/mL in patients with progressive disease. In addition, the OS of patients with D-dimer levels <1.0 μg/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0 μg/mL (22.0 vs 7.0 months, P = 0.009). The lower D-dimer levels (<1.0 μg/mL) at the first response evaluation after CTx was independent predictive factor for better survival in multivariate analysis (P = 0.037).This study suggests that D-dimer levels may serve as a biomarker for response to CTx and OS in patients with metastatic gastric cancer.
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Affiliation(s)
- Se-Il Go
- From the Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (S-IG, MJL, WSL, HJC, USL, MHK, H-GK, G-WL, JHK); Department of Preventive Medicine and Environmental Health Center, Gyeongsang National University School of Medicine, Jinju, Korea (RBK), Department of Pathology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (JHL); and Department of Laboratory Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (SJK)
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Kang WM, Meng QB, Yu JC, Ma ZQ, Li ZT. Factors associated with early recurrence after curative surgery for gastric cancer. World J Gastroenterol 2015; 21:5934-5940. [PMID: 26019458 PMCID: PMC4438028 DOI: 10.3748/wjg.v21.i19.5934] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Revised: 01/07/2015] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To characterize patterns of gastric cancer recurrence and patient survival and to identify predictors of early recurrence after surgery.
METHODS: Clinicopathological data for 417 consecutive patients who underwent curative resection for gastric cancer were retrospectively analyzed. Tumor and node status was reclassified according to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis classification for carcinoma of the stomach. Survival data came from both the patients’ follow-up records and telephone follow-ups. Recurrent gastric cancer was diagnosed based on clinical imaging, gastroscopy with biopsy, and/or cytological examination of ascites, or intraoperative findings in patients who underwent reoperation. Predictors of early recurrence were compared in patients with pT1 and pT2-4a stage tumors. Pearson’s χ2 test and Fisher’s exact test were used to compare differences between categorical variables. Survival curves were constructed using the Kaplan-Meier method and compared via the log-rank test. Variables identified as potentially important for early recurrence using univariate analysis were determined by multivariate logistic regression analysis.
RESULTS: Of 417 gastric cancer patients, 80 (19.2%) were diagnosed with early gastric cancer and the remaining 337 (80.8%) were diagnosed with locally advanced gastric cancer. After a median follow-up period of 56 mo, 194 patients (46.5%) experienced recurrence. The mean time from curative surgery to recurrence in these 194 patients was 24 ± 18 mo (range, 1-84 mo). Additionally, of these 194 patients, 129 (66.5%) experienced recurrence within 2 years after surgery. There was no significant difference in recurrence patterns between early and late recurrence (P < 0.05 each). For pT1 stage gastric cancer, tumor size (P = 0.011) and pN stage (P = 0.048) were associated with early recurrence of gastric tumors. Patient age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy were independent predictors of early recurrence in patients with pT2-4a stage gastric cancer (P < 0.05 each).
CONCLUSION: Age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy are independent factors influencing early recurrence of pT2-4a stage gastric cancer.
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Li P, He HQ, Zhu CM, Ling YH, Hu WM, Zhang XK, Luo RZ, Yun JP, Xie D, Li YF, Cai MY. The prognostic significance of lymphovascular invasion in patients with resectable gastric cancer: a large retrospective study from Southern China. BMC Cancer 2015; 15:370. [PMID: 25947284 PMCID: PMC4435771 DOI: 10.1186/s12885-015-1370-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Accepted: 04/25/2015] [Indexed: 12/26/2022] Open
Abstract
Background The focus of this study was to assess the impact of lymphovascular invasion (LVI) on both the recurrence of cancer and the long-term survival of Chinese patients with resectable gastric cancer (GC). Methods A retrospective analysis of the clinicopathological data for 1148 GC patients who had undergone gastrectomy with regional lymphadenectomy was performed. The primary objective was to assess the correlation between LVI and post-surgery outcomes for each patient. This was done by routine H & E staining for LVI on patients’ disease-free survival (DFS) and disease-specific survival (DSS). Results LVI was detected in 404 (35.2%) of the 1148 GC patients. The presence of LVI was significantly correlated with the level of CA19-9, the tumor size, the Lauren classification, tumor differentiation, gastric wall invasive depth, lymph node involvement, distant metastasis and an advanced TNM stage. There was a lower DFS and DSS in the patients with LVI as compared to the patients without LVI. A multivariate analysis also identified LVI as an independent prognostic factor of both DSS and DFS. Conclusions The presence of LVI is a risk factor for the recurrence of cancer and an independent indicator of a poor outcome in GC patients following surgery. The LVI status should be taken into consideration when determining the best approach for the treatment of the individual.
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Affiliation(s)
- Peng Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Hao-Qiang He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Diagnostic Imaging and Intervening Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Chong-Mei Zhu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Yi-Hong Ling
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Wan-Ming Hu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Xin-Ke Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Rong-Zhen Luo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Jing-Ping Yun
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Dan Xie
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Yuan-Fang Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Gastric & Pancreatic Surgery, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
| | - Mu-Yan Cai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. .,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, China.
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Wei B, Shi H, Lu X, Shi A, Cheng Y, Dong L. Association between the expression of T-cadherin and vascular endothelial growth factor and the prognosis of patients with gastric cancer. Mol Med Rep 2015; 12:2075-81. [PMID: 25847144 DOI: 10.3892/mmr.2015.3592] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2014] [Accepted: 02/17/2015] [Indexed: 11/05/2022] Open
Abstract
T-cadherin has been identified as a tumor-suppressor gene in several types of cancer. The present study aimed to investigate the association of the expression of T-cadherin with angiogenesis, and to evaluate its prognostic value for patients with primary gastric cancer. Gastric cancer tissues and matched adjacent tissues from 166 patients receiving surgical resection were included in the present study. The expression of T-cadherin was detected using immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. The expression of vascular epidermal growth factor (VEGF) was detected using immunohistochemistry, and its association with the expression of T-cadherin was analyzed. In addition, the association between the expression of T-cadherin and clinicopathological features were analyzed. The mRNA and protein expression levels of T-cadherin were significantly lower in the gastric cancer tissue compared with the corresponding adjacent normal tissue (P<0.05). The expression of VEGF was not associated with the expression of T-cadherin in the gastric cancer tissue. The decreased protein expression of T-cadherin correlated with smoking, larger tumor size (diameter, >4 cm), lymph node metastasis and a higher tumor-lymph node-metastasis stage (P<0.05 or P<0.01). However, the expression of T-cadherin was not correlated with gender, age, alcohol intake, Helecobacter pylori infection or differentiation (P>0.05). The multivariate analysis demonstrated that the expression of T-cadherin was an independent prognostic factor for the overall survival rate of patients with gastric cancer. This data suggested that the downregulation of T-cadherin may contribute to gastric cancer progression, representing a useful biomarker for predicting the biological behavior and prognosis of gastric cancer. However, no significant association was observed between the expression of VEGF and T-cadherin.
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Affiliation(s)
- Bin Wei
- Department of Gastroenterology, Xi'an No. 1 Hospital, Xi'an, Shaanxi 710002, P.R. China
| | - Haitao Shi
- Department of Gastroenterology, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Xiaolan Lu
- Department of Gastroenterology, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Ameng Shi
- Department of Gastroenterology, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Yan Cheng
- Department of Gastroenterology, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Lei Dong
- Department of Gastroenterology, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
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Mocellin S, Nitti D. Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials. Cancer Treat Rev 2015; 41:448-54. [PMID: 25814393 DOI: 10.1016/j.ctrv.2015.03.003] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Revised: 03/09/2015] [Accepted: 03/11/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival. MATERIALS AND METHODS We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for both overall (OS), disease-specific (DSS) and disease-free survival (DFS). The quality of the available evidence was assessed using the GRADE system. RESULTS Eight RCTs enrolling 2515 patients were eligible. The meta-analysis of four RCTs (n=1599) showed a significant impact of D2 versus D1 lymphadenectomy on DSS (summary HR=0.807, CI: 0.705-0.924, P=0.002), the corresponding number-to-treat being equal to ten. This effect remained clinically valuable even after adjustment for postoperative mortality. However, the quality of evidence was graded as moderate due to inconsistency issues. When OS and DFS were considered, the meta-analysis of respectively five (n=1653) and three RCTs (n=1332) found no significant difference between D2 and D1 lymph node dissection (summary HR=0.911, CI: 0.708-1.172, P=0.471, and summary HR=0.946, CI: 0.840-1.066, P=0.366, respectively). However, at subgroup analysis D2 type resulted superior to D1 type lymphadenectomy in terms of OS considering the two RCTs carried out in Eastern countries (summary HR=0.627, CI: 0.396-0.994, P=0.047). As regards the D3 vs D2 comparison, the meta-analysis of the three available RCTs (n=862) showed no significant impact of more extended lymphadenectomy on OS (summary HR=0.990, CI: 0.814-1.205, P=0.924). CONCLUSIONS Our findings support the superiority of D2 versus D1 lymphadenectomy in terms of survival benefit. However, this advantage is mainly limited to DSS, the level of evidence is moderate, and the interaction with other factors affecting patient survival (such as complementary medical therapy) remains to be elucidated.
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Affiliation(s)
- Simone Mocellin
- Surgery Branch, Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
| | - Donato Nitti
- Surgery Branch, Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
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The 7th AJCC/UICC TNM staging system may be not suitable in predicting prognosis of synchronous multiple gastric carcinoma patients with D2 gastrectomy. Tumour Biol 2015; 36:3653-9. [PMID: 25566962 DOI: 10.1007/s13277-014-3003-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 12/19/2014] [Indexed: 10/24/2022] Open
Abstract
To assess the suitability of the 7th AJCC/UICC TNM staging system in predicting the prognosis of synchronous multiple gastric carcinomas (SMGCs). A total of 129 SMGC patients who underwent gastrectomy with D2 lymphadenectomy from January 1999 to January 2009 were enrolled in this study. The location, diameter, and depth of invasion of the main tumor were all related to prognosis (P < 0.05). Multivariate analysis revealed depth of invasion as an independent predictive factor for survival (P < 0.05). Interestingly, logistic regression analysis showed that the 7th AJCC/UICC N staging system was unable to significantly predict survival in SMGCS patients (P > 0.05). Cut-point survival analysis identified the most appropriate cut-offs for metastatic lymph nodes (MLNs) as 0, 1, 6, 10, and 19: patients with 0, 1-6, 7-10, and 11-19, and ≥ 20 MLNs had median survival times of 70, 56, 35, 52, and 32 months, respectively. Multivariate analysis suggested this new categorization of MLNs to be a significant predictor of survival (P < 0.05). Preoperative assessment of depth of invasion can help in the prognosis of SMGCs patients. The 7th UICC TNM staging system may be not suitable for SMGC patients and needs improvement for rational grading of SMGCs.
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