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1.
Cancer Res Treat ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33677846

RESUMO

Purpose: This study aimed to evaluate the effect of preoperative tumour staging deviation (PTSD) on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (RGGC). Materials and Methods: Clinicopathological data of 2 346 patients who underwent RGGC were retrospectively analysed. The preoperative tumour-lymph node-metastasis (TNM) under-staging group (uTNM) comprised patients who had earlier preoperative TNM than postoperative TNM, and the no preoperative under-staging group (nTNM) comprised the remaining patients. Results: There were 1 031 uTNM (44.0%) and 1 315 nTNM cases (56.0%). Cox prognostic analysis revealed that PTSD independently affected the overall survival (OS) after surgery. The 5-year OS was lower in the uTNM group (41.8%) than in the nTNM group (71.6%). The patients less than 65 years old, with lower ASA score, 2~5 cm tumour located at the lower stomach, and cT1 or cN0 preoperative staging would more likely undergo D1+ LND in uTNM (p < 0.05). Logistic analyses revealed that tumour size >2 cm and BMI ≤22.72 kg/m2 were independent risk factors of preoperative TNM tumour under-staging in patients with cT1N0M0 staging (p < 0.05). Conclusion: Underestimated tumour staging is not rare, which possibly results in inadequate LND and affects the long-term survival for patients undergoing RGGC. D2 LND should be carefully performed in patients who are predisposed to this underestimation.

2.
Ann Surg Oncol ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768400

RESUMO

BACKGROUND: The application of splenic hilar lymph node (no. 10 LN) dissection (no. 10 LND) for proximal gastric cancer (PGC) remains controversial. This study aimed to investigate the clinical relevance of no. 10 LND from the perspective of long-term survival. METHODS: The main study population included 995 previously untreated patients who underwent laparoscopic radical total gastrectomy between January 2008 and December 2014. Of these 995 patients, 564 underwent no. 10 LND (no. 10D+ group) and the remaining 431 patients did not (no. 10D- group). Propensity score-matching was applied to reduce the effects of confounding factors. The study end points were overall survival (OS) and disease-free survival (DFS). Additionally, 39 patients who received neoadjuvant chemotherapy during the same period also were included as a separate population for analysis. RESULTS: The metastasis rate for no. 10 LN was 10.5 % (59/564). No significant differences were observed in intra- and postoperative complications nor in mortality between the no. 10D+ and no. 10D- groups (all P > 0.05). After 1:1 matching, the two groups were comparable in clinicopathologic characteristics. The no. 10D+ group had significantly better survival than the no. 10D- group (5-year OS: 63.3 % vs 52.2 %, P = 0.003; 5-year DFS: 60.4 % vs 48.1 %, P = 0.013). For the patients who received neoadjuvant chemotherapy, the 5-year OS rates in the no. 10D+ and no. 10D- groups were respectively 50.6 % and 31.3 % (P = 0.150) and the 5-year DFS rates were respectively 51.5 % and 31.3 % (P = 0.123). CONCLUSIONS: Patients with untreated PGC may achieve the benefit of long-term survival from no. 10 LND. For patients with PGC who undergo neoadjuvant chemotherapy, no. 10 LND may not bring survival benefits. However, further validation with a large-sample study is needed.

3.
Ann Surg ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33491975

RESUMO

OBJECTIVE: To compare the short-term outcomes, surgery burden, and technical performance of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) for gastric cancer (GC). SUMMARY BACKGROUND DATA: The impact of robotic systems on total gastrectomy remains obscure. METHODS: This prospective study included 50 patients with advanced proximal GC underwent RTG combined with spleen-preserving splenic hilar lymphadenectomy between March 2018 and February 2020. Patients who underwent LTG in the FUGES-002, http://links.lww.com/SLA/C929 study were enrolled to compare the outcomes between RTG and LTG. RESULTS: After propensity score matching, 48 patients in the RTG group and 96 patients in the LTG group were included in the analysis. The RTG group had a lower volume of intraoperative blood loss than the LTG group (38.7 vs. 66.4 mL, P = 0.042). Significantly more extraperigastric lymph nodes were retrieved in the RTG group than in the LTG group (20.2 vs. 17.5, P = 0.039). The average number of errors was lower in the RTG group than in the LTG group (43.2 vs. 53.8 times/case, P < 0.001). The RTG group had a higher technical skill score (30.2 vs. 28.4, P < 0.001) and a lower surgery task load index (33.2 vs. 39.8, P < 0.001) than the LTG group. No significant difference was found in terms of postoperative morbidity between the two groups (14.6% vs. 16.7%, P = 0.748). CONCLUSIONS: In complex TG for GC, compared with traditional laparoscopic surgery, robotic surgery provides a technically superior operative environment and reduces surgeon workload at high-volume specialized institutions.

4.
Nat Commun ; 11(1): 6352, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311518

RESUMO

Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISSGC) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISSGC is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISSGC can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status.


Assuntos
Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Proteína HMGB1/metabolismo , Neoplasias Gástricas/imunologia , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Moléculas de Adesão Celular/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Lectinas/metabolismo , Masculino , Pessoa de Meia-Idade , Nectinas/metabolismo , Estadiamento de Neoplasias , Prognóstico , Receptores Virais/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo
5.
Front Oncol ; 10: 574611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194683

RESUMO

Background: The benefit of adjuvant chemotherapy varies widely among patients with stage II/III gastric cancer (GC), and tools predicting outcomes for this patient subset are lacking. We aimed to develop and validate a nomogram to predict recurrence-free survival (RFS) and the benefits of adjuvant chemotherapy after radical resection in patients with stage II/III GC. Methods: Data on patients with stage II/III GC who underwent R0 resection from January 2010 to August 2014 at Fujian Medical University Union Hospital (FMUUH) (n = 1,240; training cohort) were analyzed by Cox regression to identify independent prognostic factors for RFS. A nomogram including these factors was internally and externally validated in FMUUH (n = 306) and a US cohort (n = 111), respectively. Results: The multivariable analysis identified age, differentiation, tumor size, number of examined lymph nodes, pT stage, pN stage, and adjuvant chemotherapy as associated with RFS. A nomogram including the above 7 factors was significantly more accurate in predicting RFS compared with the 8th AJCC-TNM staging system for patients in the training cohort. The risk of peritoneal metastasis was higher and survival after recurrence was significantly worse among patients calculated by the nomogram to be at high risk than those at low risk. The nomogram's predictive performance was confirmed in both the internal and external validation cohorts. Conclusion: A novel nomogram is available as a web-based tool and accurately predicts long-term RFS for GC after radical resection. The tool can also be used to determine the benefit of adjuvant chemotherapy by comparing scores with and without this intervention.

6.
Front Oncol ; 10: 550526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102217

RESUMO

Background and Objective: No specialized prognostic model for patients with gastric cancer with peritoneal metastasis (GCPM) exists for intraoperative clinical decision making. This study aims to establish a new prognostic model to provide individual treatment decisions for patients with GCPM. Method: This retrospective analysis included 324 patients with GCPM diagnosed pathologically by laparoscopy from January 2007 to January 2018 who were randomly assigned to different sets (227 in the training set and 97 in the internal validation set). A nomogram was established from preoperative and intraoperative variables determined by a Cox model. The predictive ability and clinical applicability of the PM nomogram (PMN) were compared with the 15th Japanese Classification of Gastric Carcinoma (JCGC) Staging Guidelines for PM (P1abc). Additional external validation was performed using a dataset (n = 39) from the First Affiliated Hospital of University of Science and Technology of China. Results: The median survival time was 8 (range, 1-90) months. In the training set, each PMN substage had significantly different survival curves (P < 0.001), and the PMN was superior to the P1abc based on the results of time-dependent receiver operating characteristic curve, C-index, Akaike information criterion and likelihood ratio chi-square analyses. In the internal and external validation sets, the PMN was also better than the P1abc in terms of its predictive ability. Of the PMN1 patients, those undergoing palliative resection had better overall survival (OS) than those undergoing exploratory surgery (P < 0.05). Among the patients undergoing exploratory surgery, those who received chemotherapy exhibited better OS than those who did not (P < 0.05). Among the patients who received palliative resection, only PMN1 patients exhibited better OS following chemotherapy (P < 0.05). Conclusion: We developed and validated a simple, specific PM model for patients with GCPM that can predict prognosis well and guide treatment decisions.

7.
Aging (Albany NY) ; 12(19): 18982-19011, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052878

RESUMO

The effect of POC1 centriolar protein A (POC1A) on gastric cancer (GC) has not been clearly defined. In this study, POC1A expression and clinical information in patients with GC were analyzed. Multiple databases were used to investigate the genes that were co-expressed with POC1A and genes whose changes co-occurred with genetic alternations of POC1A. Moreover, the TISIDB and TIMER databases were used to analyze immune infiltration. The GSE54129 GC dataset and LASSO regression model (tumor vs. normal) were employed, and 6 significant differentially expressed genes (LAMP5, CEBPB, ARMC9, PAOX, VMP1, POC1A) were identified. POC1A was selected for its high expression in adjacent tissues, which was confirmed with IHC. High POC1A expression was related to better overall and recurrence-free survival. GO and KEGG analyses demonstrated that POC1A may regulate the cell cycle, DNA replication and cell growth. Furthermore, POC1A was found to be correlated with immune infiltration levels in GC according to the TISIDB and TIMER databases. These findings indicate that POC1A acts as a tumor suppressor in GC by regulating the cell cycle and cell growth. In addition, POC1A preferentially regulates the immune infiltration of GC via several immune genes. However, the specific mechanism requires further study.

8.
BMC Cancer ; 20(1): 1002, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059606

RESUMO

BACKGROUND: The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy. METHODS: This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS). RESULTS: In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (all p > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%, p = 0.004; RFS: 52.54% vs 68.35%, p = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%, p = 0.007; RFS: 51.43% vs 74.36%, p = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC (p < 0.05). CONCLUSIONS: Sarcopenia is not related to the short-term prognoses of patients with g-NENs. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery.

9.
Ann Surg ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32889876

RESUMO

OBJECTIVE: To evaluate the short-term outcomes of patients with gastric cancer (GC) who received robotic distal gastrectomy (RDG) or laparoscopic distal gastrectomy (LDG). SUMMARY BACKGROUND DATA: Despite the increasing use of RDG in patients with GC, its safety and efficacy compared to those of LDG have not been elucidated in a randomized controlled trial (RCT). METHODS: Three hundred patients with cT1-4a and N0/+ between September 2017 and January 2020 were enrolled in this RCT at a high-volume hospital in China. The short-term outcomes were compared between the groups. RESULTS: The modified intention-to-treat analysis included data from 283 patients (RDG group: n = 141) and (LDG group: n = 142). Patients in the RDG group exhibited faster postoperative recovery, milder inflammatory responses, and reduced postoperative morbidity (9.2% vs. 17.6%, respectively, p = 0.039). Higher extraperigastric lymph nodes (LNs) were retrieved in the RDG group (17.6 ±â€Š5.8 vs. 15.8 ±â€Š6.6, p = 0.018) with lower noncompliance rate (7.7% vs. 16.9%, respectively, p = 0.006). Additionally, patients in the RDG group were more likely to initiate adjuvant chemotherapy earlier (median [interquartile range] postoperative days: 28 [24-32] vs. 32 [26-42], p = 0.003). Although total hospital costs were higher in the robotic group than in the laparoscopic group, the direct cost was lower for RDG than for LDG (all p < 0.001). CONCLUSIONS: RDG is associated with a lower morbidity rate, faster recovery, milder inflammatory responses, and improved lymphadenectomy. Additionally, faster postoperative recovery in the RDG group enables early initiation of adjuvant chemotherapy. Our results provide evidence for the application of RDG in patients with GC.

10.
Oncologist ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32864840

RESUMO

BACKGROUND: The benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging. PATIENTS AND METHODS: Clinicopathological data of 1,791 patients who underwent curative-intent gastrectomy after neoadjuvant therapy in the Surveillance, Epidemiology, and End Results database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th edition ypTNM staging and the modified staging for patients after neoadjuvant therapy. RESULTS: In the development cohort, the 5-year OS for AJCC stages I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stages IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C-index: 0.620 vs. 0.589, p < .001), predictive homogeneity (likelihood ratio chi-square: 140.71 vs. 218.66, p < .001), predictive accuracy (mean difference in Bayesian information criterion: 64.94; net reclassification index: 35.54%; integrated discrimination improvement index: 0.032; all p < .001), and model stability (time-dependent receiver operating characteristics curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p < .05). CONCLUSION: We have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with GC after neoadjuvant therapy. IMPLICATIONS FOR PRACTICE: The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. Based on multi-institutional data, this study developed a modified ypTNM staging, which is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with gastric cancer after neoadjuvant therapy.

11.
Eur J Surg Oncol ; 46(12): 2221-2228, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32859432

RESUMO

OBJECTIVE: To investigate a reasonable lymph node (N) staging system for gastric cancer patients with ≤15 retrieved lymph nodes (LNs). METHODS: The clinicopathological and follow-up data of patients with ≤15 LNs were obtained from the US Surveillance, Epidemiology, and End Results (SEER) database to analyze the impact of the number of retrieved LNs and metastatic status on the prognosis. In addition, external validation was achieved with data from two medical centers in China. RESULTS: A total of 18,139 gastric cancer patients with 1-15 retrieved LNs from the SEER database were enrolled and randomly divided into the training group and the internal validation group. A new LN staging system, mNr staging (mNr0-4; 5 stages), was established according to the number of retrieved LNs and the metastatic rate. Compared with the TNM and TNrM staging systems (established by Wang J; misclassification rates of 50.4% and 62.5%, respectively), the mTNrM staging system had a lower misclassification rate (23.4%). Furthermore, there was a significant difference in the 5-year overall survival (OS) rate between the mTNrM staging subgroups (p < 0.05); however, no significant difference was found in the 5-year OS rate of partial adjacent stages in the TNM (8th edition) and TNrM (p > 0.05) staging systems. Similar results were obtained in the external validation cohort. CONCLUSION: mNr and mTNrM staging systems can efficiently distinguish a survival difference in patients who undergo gastrectomy with ≤15 retrieved LNs, with more accurate predictions of the 5-year OS rate of patients compared with the TNM and TNrM staging systems.

12.
Front Oncol ; 10: 1149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850326

RESUMO

Background: To investigate the prognostic effects and risk factors of the omission and delay of postoperative chemotherapy of stage II/III gastric cancer (GC). Methods: The clinicopathological data of 1,520 patients undergoing radical gastrectomy for stage II/III GC were collected and retrospectively analyzed. We defined the chemotherapy delayed until more than 60 days after radical gastrectomy and the complete omission of chemotherapy as unacceptable chemotherapy initiation (UAC), whereas the chemotherapy conducted within 60 days of radical gastrectomy was defined as acceptable chemotherapy initiation (AC). The survival between the two groups was compared, and the trends and risk factors of UAC were analyzed. Results: There were 539 (35.5%) patients with UAC. The overall survival (OS) and disease-free survival of the UAC group patients were significantly inferior to those in the AC group (p < 0.001). Cox multivariate analysis demonstrated that UAC is an independent predictor of OS (p < 0.05). The OS and disease-free survival of the patients in the UAC group were close to those of the patients without chemotherapy (p > 0.05). Logistic analysis showed that female, old age, a self-paid status, a very low social status, high American Society of Anesthesiologists scores, intra-abdominal surgery history, and serious postoperative complications were independent risk factors of UAC (all p < 0.05). The radar chart shows the risk factors of UAC changed with time. Conclusions: UAC after radical gastrectomy is an independent risk factor for the prognosis of stage II/III GC patients. However, no significant decline of UAC has been achieved recently and should call for the attention of both government and clinicians.

13.
Br J Cancer ; 123(7): 1131-1144, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32606358

RESUMO

BACKGROUND: Toward identifying new strategies to target gastric cancer stem-like cells (CSCs), we evaluated the function of the tumour suppressor CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) in gastric CSC maintenance. METHODS: We examined the expression of CDK5RAP3 and CD44 in gastric cancer patients. The function and mechanisms of CDK5RAP3 were checked in human and mouse gastric cancer cell lines and in mouse xenograft. RESULTS: We show that CDK5RAP3 is weakly expressed in gastric CSCs and is negatively correlated with the gastric CSC marker CD44. CDK5RAP3 overexpression decreased expression of CSC markers, spheroid formation, invasion and migration, and reversed chemoresistance in gastric CSCs in vitro and vivo. CDK5RAP3 expression was found to be regulated by extracellular-related kinase (ERK) signalling. ERK inhibitors decreased spheroid formation, migration and invasion, and the expression of epithelial-to-mesenchymal transition (EMT)-related proteins in both GA cells and organoids derived from a genetically engineered mouse model of GA. Finally, CDK5RAP3 expression was associated with reduced lymph-node metastasis and better prognosis, even in the presence of high expression of the EMT transcription factor Snail, among patients with CD44-positive GA. CONCLUSIONS: Our results demonstrate that CDK5RAP3 is suppressed by ERK signalling and negatively regulates the self-renewal and EMT of gastric CSCs.

14.
Gastric Cancer ; 2020 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-32712769

RESUMO

BACKGROUND: For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. METHODS: A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. RESULTS: No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. CONCLUSIONS: LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

15.
BMC Cancer ; 20(1): 638, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646396

RESUMO

BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers. For colorectal cancer, a benefit that was associated with postdiagnosis aspirin use was observed for overall survival and cancer-specific survival [HR = 0.83, 95%CI(0.75, 0.9.);HR = 0.78, 95%CI(0.66, 0.92), respectively. However, a prediagnosis of aspirin use did not provide a benefit for overall or cancer-specific survival in colorectal cancer. HR values for overall and cancer-specific survival benefits for colorectal cancer associated with both prediagnosis and postdiagnosis aspirin were as follows: HR = 0.75, 95%CI(0.61, 0.92) and HR = 0.78, 95%CI(0.73, 0.85), respectively. In addition, the survival benefit of postdiagnosis aspirin use appeared to be confined to patients with mutated PIK3CA tumors [HR = 0.78, 95%CI(0.50, 0.99)] and was positive for PTGS2 (COX-2) expression [HR = 0.75, 95%CI(0.43, 1.30)]. CONCLUSIONS: These findings provide further indications that postdiagnosis aspirin use improves overall survival and cancer-specific survival in colorectal cancer, especially for patients who are positive for PTGS2 (COX-2) expression and PIK3CA-mutated tumors. However, aspirin therapy does not improve overall survival in esophageal and gastric cancers, although the meta-analysis was mainly limited to retrospective studies.

16.
Mol Cancer ; 19(1): 114, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650804

RESUMO

BACKGROUND: BATF2, also known as SARI, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. METHODS: We obtained GC tissues and corresponding normal tissues from 8 patients and identified BATF2 as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine BATF2 levels in normal and GC tissues. The prognostic value of BATF2 was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of BATF2 in GC growth and metastasis were evaluated in vitro and in vivo. RESULTS: BATF2 expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that BATF2 was an independent prognostic factor and effective predictor in patients with GC. Low BATF2 expression was remarkably associated with peritoneal recurrence after curative gastrectomy. Moreover, elevated BATF2 expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, BATF2 binds to p53 and enhances its protein stability, thereby inhibiting the phosphorylation of ERK. Tissue microarray results indicated that the prognostic value of BATF2 was dependent on ERK activity. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA by METTL3 repressed its expression in GC. CONCLUSIONS: Collectively, our findings indicate the pivotal role of BATF2 in GC and highlight the regulatory function of the METTL3/BATF2/p53/ERK axis in modulating GC progression, which provides potential prognostic and therapeutic targets for GC treatment.

17.
Eur J Surg Oncol ; 46(10 Pt B): e7-e13, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32709375

RESUMO

Most gastric cancer (GC) cases are diagnosed at an advanced stage in China. Because of its high morbidity and mortality, GC remains a major health crisis in China. Surgical resection is the only potentially curative treatment for GC. Owing to being minimally invasive, laparoscopic radical gastrectomy has been widely used in various countries, especially in East Asia, since Kitano first reported the feasibility and safety of this technique. Although laparoscopic gastric surgery was introduced relatively late in China, Chinese surgeons have made unique contributions to the research and clinical practice of laparoscopic gastric surgery due to the large number of clinical cases. This review focuses on the progress in laparoscopic gastrectomy for advanced stage GC in China, including reasonable approaches in different areas and oncologic efficacy of laparoscopic surgery, and introduce advanced technology to facilitate surgeons to rapidly overcome the learning curve in clinical practice.

18.
Br J Cancer ; 123(3): 418-425, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32451469

RESUMO

BACKGROUND: In clinical practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most common markers measured before and after surgery for gastric cancer (GC). However, which pre- or post-operative combined tumour markers (CEA and CA19-9) have more prognostic value remains unclear. METHODS: Consecutive patients undergoing a resection for GC at the Fujian Medical University Union Hospital were included as a discovery database between January 2011 and December 2014. The prognostic impact of pre- and post-operative tumour markers was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The results were then externally validated. RESULTS: A total of 735 and 400 patients were identified in the discovery cohort and in the validation cohort, respectively. Overall survival rates decreased in a stepwise manner in association with the number of pre- and post-operative positive tumour markers (both P < 0.001). Multivariable analysis revealed that the number of pre-operative positive tumour markers was an independent prognostic factor (P < 0.05). For patients with abnormal pre-operative tumour markers, normalisation of tumour markers after surgery is an independent prognostic protective factor (hazard ratio (HR) = 0.618; 95% confidence interval (CI) = 0.414-0.921), and patients with both positive post-operative tumour markers had double the risk of overall death (HR = 2.338; 95% CI = 1.071-5.101). Similar results were observed in the internal validation and external validation cohorts. CONCLUSION: Pre-operative tumour markers have a better discriminatory ability for post-operative survival in GC patients than post-operative tumour markers, and the normalisation of tumour markers after surgery was associated with better survival.

19.
Asian J Surg ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32467008

RESUMO

BACKGROUND: Compared with other histologic types, signet ring cell gastric carcinoma (SRC) has unique oncological characteristics, and its implication on the prognosis of gastric cancer patients remains unclear. The purpose of this study was to evaluate the prognostic impact of body mass index (BMI) on SRC patients. METHODS: A retrospective analysis was performed using the clinical records of 3342 patients with SRC or tubular adenocarcinoma who underwent radical gastrectomy between 2000 and 2014. Patients were divided into three groups according to histologic subtype: SRC, well-to-moderately differentiated adenocarcinoma (WMD), and poorly differentiated adenocarcinoma (PD). We compared the survival of SRC patients with that of tubular adenocarcinoma patients according to BMI. RESULTS: The 5-year survival of SRC was significantly worse than that of WMD (P < 0.001) but superior to that of PD (P < 0.001). BMI-stratified analysis showed that in the high-BMI group, the prognosis of SRC was similar to that of WMD (P > 0.05) and better than that of PD (P < 0.001). In normal-BMI patients, SRC had a worse prognosis than WMD (P < 0.001) but a more favorable prognosis than PD (P < 0.001). SRC among low-BMI patients displayed much poorer survival than did both WMD (P < 0.001) and PD (P = 0.005). Multivariate analysis indicated that the risk of death was the lowest in SRC patients with a high BMI and highest for SRC patients with a low BMI (low-BMI hazard ratio: SRC 1 vs. WMD 0.51 and PD 0.53). CONCLUSION: SRC has worse prognostic impact as BMI decreases. BMI leads to differing prognosis of SRC compared with tubular adenocarcinoma.

20.
J Cancer ; 11(12): 3483-3491, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32284744

RESUMO

Objective: To evaluate the prognostic significance of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging classification for gastric cancer. Methods: Prospective databases were reviewed to identify patients who underwent radical gastrectomy at two specialized eastern centers. The prognostic value of the eighth edition TNM classification was estimated and compared with that of the seventh edition. Additional external validation was performed using a dataset from a Western population. Results: Significant differences in 5-year overall survival (OS) rates were observed for each TNM stage when using the eighth edition system, and smaller Akaike information criteria (AIC) values and a higher c-statistic were observed relative to those of the seventh edition. However, the OS rates in each subgroup of stage III patients based on the eighth edition were significantly different. Patients with the same pN stage, namely, the pT4a and pT4b groups, showed similar 5-year OS (P>0.05). Based on the survival data, we propose a simplified staging system. In the improved TNM (iTNM) staging system, the subgroups of a given TNM stage do not show statistically significant differences in OS. The iTNM staging exhibits superior prognostic stratification, with lower AIC values and a higher c-statistic than the eighth edition TNM classification. Similar results were obtained with the external validation dataset from the IMIGASTRIC database. Conclusion: The prognostic prediction of the eighth edition of the AJCC TNM classification is superior to that of the seventh edition. However, it remains associated with some stage migration. The iTNM staging system permits simplification and slightly better prognostic prediction.

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