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Purpose: IKAROS family zinc finger 3 (IKZF3) is an oncogene involved in different malignancies, particularly in the development and malignant progression of lymphocytes. However, IKZF3 amplification and clinical significance in gastric cancers (GCs) remain unexplored., Methods: We examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays., Results: IKZF3 amplification was detected in 6.9% (28/404) of all GC patients, with higher rates in intestinal-type gastric cancer (IGC) (11.22%, 22/196) compared to other types (2.88%, 6/208). HER2 amplification was identified in 16.09% (65/404) of all GC patients, with higher rates in IGC (20.92%, 41/196) compared to other types (11.54%, 24/208). Co-amplification of IKZF3 and HER2 was detected in 8.16% (16/196) of IGC patients and in 2.40% (5/208) of other types. IKZF3 amplification showed significant correlation with IGC (P = 0.001) and HER2 amplification (P = 0.0001). IKZF3 amplification exhibited significantly worse disease-free survival (DFS) (P = 0.014) and overall survival (OS) (P = 0.018) in GC patients, particularly in IGC (DFS: P < 0.001; OS: P < 0.001), rather than other types. Cox regression analysis demonstrate IKZF3 amplification as an independent poor prognostic factor in all GCs (P = 0.006, P = 0.004 respectively) and in IGC patients, regardless of stages I-II or III-IV (P = 0.007, P = 0.004 respectively). On the other hand, HER2 amplification was significantly associated with worse DFS (P = 0.008) and OS (P = 0.01) in IGC patients, but not in all GCs and in multivariate analysis. Within the subset of patients with HER2 amplification, those also exhibiting IKZF3 amplification displayed potential poorer prognosis (P = 0.08, P = 0.11 respectively)., Conclusion: IKZF3 amplification was detected in minority of GC patients, especially in IGC, and was an independent indicator of poor prognosis. Our study, for the first time, found the prognostic value of IKZF3 was superior to HER2 for GC patients., (© 2024. The Author(s).)

Background: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies., Purpose: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC., Methods: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity., Results: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca 2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine., Conclusion: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca 2+ -dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies., (© 2024. The Author(s).)

Abnormal activation of fibroblast growth factor receptors (FGFRs) results in the development and progression of human cancers. FGFR2 is frequently amplified or mutated in cancers; therefore, it is an attractive target for tumor therapy. Despite the development of several pan-FGFR inhibitors, their long-term therapeutic efficacy is hindered by acquired mutations and low isoform selectivity. Herein, we report the discovery of an efficient and selective FGFR2 proteolysis-targeting chimeric molecule, LC-MB12, that incorporates an essential rigid linker. LC-MB12 preferentially internalizes and degrades membrane-bound FGFR2 among the four FGFR isoforms; this may promote greater clinical benefits. LC-MB12 exhibits superior potency in FGFR signaling suppression and anti-proliferative activity compared to the parental inhibitor. Furthermore, LC-MB12 is orally bioavailable and shows significant antitumor effects in FGFR2-dependent gastric cancer in vivo. Taken together, LC-MB12 is a candidate FGFR2 degrader for alternative FGFR2-targeting strategies and offers a promising starting point for drug development.

Responses toward preoperative chemotherapy are heterogeneous in patients with gastric adenocarcinoma. Existing studies in the field focus heavily on the tumor microenvironment (TME), whereas little is known about the relationship between systemic immunity and chemotherapy response. In this study, we collect serum samples from patients with gastric adenocarcinoma before, on, and after preoperative chemotherapy and study their immune proteomics using an antibody-based proteomics panel. We also collect surgically resected tumor samples and incorporate multiple methods to assess their TME. We find that both local and systemic immune features are associated with treatment response. Preoperative chemotherapy induces a sophisticated systemic immune response indicated by dynamic serum immune proteomics. A pretreatment serum protein scoring system is established for response prediction. Together, these findings highlight the fundamental but largely underestimated role of systemic immunity in the treatment of gastric cancer, suggesting a patient stratification strategy based on pretreatment serum immune proteomics., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate the clinical relevance of exosomal HER2 (Exo HER2) level in assessing the tissue HER2 status and predicting the efficacy of trastuzumab treatment., Methods: In this prospective study, patients with advanced gastric cancer (AGC) from three hospitals between August 2016 to November 2020 were enrolled. The Exo HER2 level was detected by enzyme-linked immunosorbent assay. Receiver operating characteristic curve (ROC) was drawn referring to the HER2 tissue status to assess the diagnostic value of Exo HER2. Cox proportional hazards regression and logistic regression were used to evaluate the association between Exo HER2 and progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients who received trastuzumab-based first-line therapy., Results: In this study, 242 patients with advanced or metastatic gastric adenocarcinoma were registered. Of these, 238 AGC patients were eligible for evaluating serum-derived exosome HER2 diagnostic value, including 114 HER2-positive. Finally, 64 were eligible for efficacy analysis. The area under the ROC curve was 0.746. The optimal cutoff value for diagnosing tissue HER2-positive status was 729.95 ng/ml, with a sensitivity of 66.7% and a specificity of 74.2%. In 64 patients treated with trastuzumab, higher baseline Exo HER2 level indicated better prognosis. 844 ng/ml and 723 ng/ml were the right cutoffs for distinguishing the population with superior PFS (hazard ratio [HR] = 0.41, P = 0.017) and OS (HR = 0.30, P < 0.001), respectively., Conclusion: Serum exosomal HER2 level might serve as an effective biomarker for assessing tissue HER2 status in AGC and screening the potential patients who might benefit from anti-HER2 therapy., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Glomus tumor is a relatively uncommon soft tissue neoplasm predominantly occurring in upper extremity (fingers), less reported in stomach. This study aimed to discuss the clinicopathologic features of gastric glomus tumor (GGT) and then provide reference for clinical practice. Methods: A retrospective analysis of all cases pathologically diagnosed of GGT was performed, pathological findings were correlated with clinical information, immunohistochemical studies, next-generation sequencing, and patient follow-ups. A review of literature by searching similar cases was conducted to summarize previous knowledge of GGTs. Results: Our study identified 15 GGTs included 5 males and 10 females, aged between 35-75 years old (median, 49 years old). The tumor was located to the gastric corpus in 6 cases (40%) and to the antrum in 9 cases (60%). The maximum tumor diameter ranged between 1-4 cm (median, 1.5 cm). There were 11 cases (73%) of solid glomus tumor, 3 cases (20%) of mixture of solid glomus tumor and glomangioma, and 1 case (7%) of glomangiomyoma. Partial spindle cell area was observed in 3 cases (20%), moderate cellular atypia in 1 case (7%), atypical mitosis in 1 case (7%), vascular invasion in 5 cases (33%), neural invasion in 6 cases (40%) and tumor necrosis in 1 case (7%). Tumor cells expressed Collagen type IV, α-smooth muscle actin (α-SMA), and synaptophysin in most cases. The Ki67 index varied from 1% to 30%. Next-generation sequencing reported EGFR, PIK3CA, KEAP1 and TP53 mutation . The outcome information was obtained in 12 (80%) cases, followed for 6-63 months, 11 patients (92%) had tumor-free survival and 1 patient (8%) developed liver metastasis 26 months after surgery. Literature review obtained 16 previously reported malignant GGT cases. In terms of the total 31 cases, univariate analysis revealed that the atypical mitosis (OS: p = 0.009; DFS: p = 0.010) and severe cellular atypia (OS: p = 0.007; DFS: p = 0.004) were significantly associated with poor prognosis (patient death). Conclusion: GGT is indolent, while long-term close follow-up should be required in the presence of increasing number of risk factors. Malignant GGT is relatively uncommon and predisposes to liver metastasis, calling for accumulation of large-sample data and experience., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deng, Luo, Huang, Luo, Song, Liang, Xu, Yuan and Hou.)

Aspongopus chinensis Dallas is used as a traditional Chinese medicine as well as an edible insect. Although its anti-tumor effects have been observed, the anti-tumor active component(s) in the hemolymph of A. chinensis remains unknown. In this study, a combination usage of ultrafiltration, gel filtration chromatography, FPLC and RP-HPLC to separate and purify active peptides was performed based on the proliferation of the human gastric cancer SGC-7901 cell line treated with candidates. One peptide (MW = 2853.3 Da) was isolated from the hemolymph of A. chinensis. A total of 24 amino acid residues were continuously determined for the active peptide: N'-ECGYCAEKGIRCDDIHCCTGLKKK-C'. In conclusion, a peptide that can inhibit the proliferation of gastric cancer SGC-7901 cells in the hemolymph of A. chinensis was purified in this study, which is homologous to members of the spider toxin protein family. These results should facilitate further works for this peptide, such as the cloning of genes, expression in vitro by prokaryotic or eukaryotic systems, more specific tests of anti-tumor activity, and so on.

Background: MM-associated circular RNA (Circ-MYBL2), a circular RNA (circRNA), participates in cancer biology. However, its role in gastric cancer (GC) is unclear. In this study, circ-MYBL2 was predicted to interact with precursor microRNA-92b (miR-92b). We then analyzed the role of circ-MYBL2 in GC and explored its crosstalk with miR-92b., Methods: In this research Circ-MYBL2 and miR-92b (mature and precursor) accumulation was determined using reverse transcription polymerase chain reaction (RT-qPCR). The involvement of circ-MYBL2 in the maturation of miR-92b was analyzed using overexpression assays. The subcellular location of circ-MYBL2 was determined using nuclear fractionation assay. The binding of precursor miR-92b to circ-MYBL2 was analyzed through RNA-RNA pulldown assay. The role of circ-MYBL2 and miR-92b in GC cell proliferation was studied with BrdU assay., Results: We found that GC tissues exhibited increased mature miR-92b levels but decreased precursor miR-92b and circ-MYBL2 levels. Circ-MYBL2 was detected in both the nucleus and cytoplasm in GC cells, and it directly interacted with precursor miR-92b. Moreover, circ-MYBL2 overexpression increased precursor miR-92b expression and decreased mature miR-92b level. Furthermore, miR-92b (mature) increased GC cell proliferation, and circ-MYBL2 decreased GC cell proliferation and suppressed the effect of miR-92b on GC cell proliferation., Conclusions: Circ-MYBL2 may absorb precursor miR-92b in the nucleus to suppress its role in promoting gastric cancer cell proliferation., Competing Interests: Conflicts of interest The authors have no conflict of interest., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Former single center studies indicated that HER2 assessment with two primary tumor blocks (dual block HER2 assessment) could be an efficient and practical approach to overcome the adverse impact of heterogeneity and acquire a HER2 positive rate in gastric cancer (GC). This multicenter prospective clinical trial (NCT02843412) was launched to verify its value and generality., Methods: A total of 3806 participants with primary GCs have been enrolled from 8 hospitals in China. Two primary tumor blocks were selected and recorded as block 1 and block 2 after histological evaluation. An HER2 (4B5) rabbit monoclonal antibody was used for the immunohistochemistry (IHC) analysis., Results: In total patients, HER2 IHC positive (3+) rate with dual block assessment (9.4%) was higher than that with single block assessment (block 1: 7.8%, block 2: 7.8%) (P < 0.001). Compared with single-block assessment, dual-block assessment increased the positive rate by approximate 20%. Similarly, HER2 equivocal (2+) rate was increased in dual block assessment (25.8%), which was higher than that in single block assessment (block 1: 20.3%, block 2: 20.9%) (P < 0.001). Conversely, dual block assessment demonstrated a lower HER2 negative (0/1+) rate (64.8%) than single block assessment (block1: 71.9%, block 2: 71.3%) (P < 0.001). These findings were also confirmed in individual hospitals., Conclusions: Dual block HER2 assessment effectively increased HER2 IHC positive rate in resected specimens of GC. We recommended dual block HER2 assessment be promoted in routine clinical practice in GC., Trial Registration: ClinicalTrials.gov, NCT02843412 . Registered 1 July 2016 - Retrospectively registered., (© 2022. The Author(s).)

Epstein-Barr virus-associated gastric cancer (EBVaGC) shows a robust response to immune checkpoint inhibitors. Therefore, a cost-efficient and accessible tool is needed for discriminating EBV status in patients with gastric cancer. Here we introduce a deep convolutional neural network called EBVNet and its fusion with pathologists for predicting EBVaGC from histopathology. The EBVNet yields an averaged area under the receiver operating curve (AUROC) of 0.969 from the internal cross validation, an AUROC of 0.941 on an external dataset from multiple institutes and an AUROC of 0.895 on The Cancer Genome Atlas dataset. The human-machine fusion significantly improves the diagnostic performance of both the EBVNet and the pathologist. This finding suggests that our EBVNet could provide an innovative approach for the identification of EBVaGC and may help effectively select patients with gastric cancer for immunotherapy., (© 2022. The Author(s).)

Background: Gastric neoplasms with fundic gland differentiation include oxyntic gland adenomas (OGAs) and gastric adenocarcinomas of fundic gland type (GA-FGs). Due to their well-differentiated and similar morphology with normal fundic glands, it is usually challenging to identify these lesions in pathological diagnosis, especially in biopsy specimens. This study aims to explore and verify the potential role of a newly developed monoclonal antibody (McAb) NJ001 (SP70) in differentiating fundic neoplasms from non-neoplastic fundic gland lesions., Methods: Twenty-three cases of histological confirmed gastric fundic gland neoplasms were obtained, including 12 cases of OGAs and 11 of GA-FGs. Fifty cases of fundic gland polyps (FGPs) were taken as the control group. Six cases of well-differentiated gastric neuroendocrine tumors (NETs) (easily misdiagnosed) were also obtained. Key clinicopathological information was collected. SP70 immunostaining was performed (with para-tumor normal fundic glands as internal control). The positive intensity and staining pattern of SP70 were analyzed and compared., Results: In normal gastric mucosa, SP70 was strongly and diffusely stained on the cytoplasm in fundic glands, but not in the foveolar epithelium. Therefore, a zonal distribution of SP70 was observed in normal mucosa. FGPs (50/50, 100%) shared a similar expression pattern with normal fundic glands. In fundic gland neoplasms, a significant down-expression of SP70 was observed in both OGAs and GA-FGs. The positive rate of SP70 in fundic gland neoplasms (6/23, 26.1%) was significantly lower than that in FGPs (100%) (P<0.0001). There was no difference in SP70 expression between OGAs (3/12, 25.0%) and GA-FGs (3/11, 27.2%) group (P>0.05). In these 6 NET cases, SP70 was weak to moderate intensity in the majority of tumor cells (with a different expression pattern)., Conclusion: Down-expression of SP70 is a specific feature to fundic gland neoplasms including OGAs and GA-FGs. Therefore, SP70 can serve as a potential biomarker in the identification and differential diagnosis of fundic gland neoplasms., (© 2022. The Author(s).)

Background: High expression of PIN1 is associated with gastric cancer progression and risk. Patients & methods: Two single-nucleotide polymorphisms in PIN1 , rs2233678 and rs2233679, were examined in gastric cancer patients using PCR-restriction fragment length polymorphism. Results: The rs2233678 GC genotype and C alleles correlated with a decreased susceptibility to gastric cancer. The stratification analysis indicated that the rs2233678 GC genotype was inversely related to gastric cancer risk in never smokers, never drinkers and patients with stage I/II disease. Males and ever drinkers carrying the rs2233679 CT genotype had a mildly elevated susceptibility to gastric cancer. Conclusion: The PIN1 single-nucelotide polymorphisms rs2233678 and rs2233679 correlate with the risk of gastric cancer.

BACKGROUND The results of previous studies that evaluated the association between pretreatment blood platelet-to-lymphocyte ratio (PLR) and clinical outcomes and chemosensitivity in patients with advanced gastric cancer are inconsistent. Therefore, this study was designed to investigate the association between pretreatment blood PLR and clinical outcomes and chemosensitivity in advanced gastric cancer patients. MATERIAL AND METHODS We performed a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library up to Mar 9, 2021. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were pooled for meta-analysis. The quality of the included studies was measured by the Newcastle-Ottawa Quality Assessment Scale. RESULTS We included 17 studies comprising 3499 patients with advanced GC in this meta-analysis. Pooled results demonstrated that high PLR was correlated with poor OS (HR=1.429, 95% CI=1.246-1.639, P<0.001) and DFS (HR=1.47, 95% CI=1.14-1.88, P=0.003) compared with low PLR in patients with advanced GC. Moreover, high PLR was associated with a lower response to chemotherapy in patients with advanced GC (OR=1.395, 95% CI=1.056-1.841, P=0.019). However, there was no significant correlation between PLR and clinicopathological features. CONCLUSIONS This meta-analysis suggests that high PLR is a risk factor for unfavorable OS, DFS, and chemosensitivity in patients with advanced GC.

Objective: To compare the clinicopathological characteristics and the prognosis of gastric adenocarcinoma patients with and without neuroendocrine differentiation (NED) after radical gastrectomy plus D2 lymph node dissection. Methods: A retrospective cohort study was performed. The inclusion criteria were as follows: (1) patients who underwent radical resection of gastric cancer plus D2 lymph node dissection and were confirmed as gastric adenocarcinoma by postoperative pathology and received immunohistochemical examination of neuroendocrine markers Syn and/or CgA; (2) patients aged 20 to 75 years with normal organ function; (3) patients who did not receive neoadjuvant chemotherapy or radiotherapy before operation; (4) patients with postoperative pathological stage I to III according to the 8th edition of tumor staging system of American Joint Committee on Cancer (AJCC); and (5) patients who completed adjuvant chemotherapy according to the postoperative pathological stage. Those who had other malignant tumors in the past 5 years and who could not be followed up according to the required rules were excluded. According to the above criteria, the clinicopathological characteristics of gastric cancer patients who underwent radical resection plus D2 lymph node dissection in Zhongshan Hospital of Fudan University from January 2010 to June 2017 were collected and compared. All patients were followed up till June 2020. The disease-free survival (DFS) and overall survival (OS) between the patients with and without NED were compared, and the effect of NED on the prognosis was corrected by Cox proportional hazards model. The propensity score matching method was used for sensitivity analysis. Results: A total of 539 patients were enrolled in this study, including 35 with NED and 504 without NED. Compared with the patients without NED, the patients with NED were older [(65.0±7.5) years vs. (54.5±11.3) years, t =-7.681, P <0.001], had higher proportion of undergoing proximal gastrectomy [22.9% (8/35) vs. 7.6% (36/504), χ(2)=10.335, P =0.006], higher proportion of intestinal-type based on Lauren classification [77.1% (27/35) vs. 42.5% (214/504), χ(2)=14.553, P <0.001], and higher proportion of pathologic stage III [65.7% (23/35) vs. 27.6% (139/504), χ(2)=25.653, P <0.001]. The 3-year DFS of patients with NED and those without NED was 48.9% (95% CI: 33.8%-70.8%) and 37.4% (95% CI: 32.9%-42.5%) respectively, and no significant difference was found ( P =0.44). The 3-year OS was 56.1% (95% CI: 39.9%-79.1%) and 64.3% (95% CI: 59.3%-69.7%) respectively, and no significant difference was found as well ( P =0.32). Univariate and multivariate analyses showed that NED was not an independent risk factor for DFS and OS (all P >0.05). Sensitivity analysis showed that there was no significant difference in DFS and OS between the two groups after propensity score matching. Conclusion: Compared with patients without NED, patients with NED were older at onset, had a higher proportion of proximal gastrectomy, intestinal-type, and later diagnostic stage, but the survival prognosis had no significant difference with that of patients without NED.

Objective: Diagnosis of gastric intestinal metaplasia (GIM) relies on gastroscopy and histopathologic biopsy, but their application in screening for GIM is limited. We aimed to identify serological biomarkers of GIM via screening in Guangdong, China., Methods: Cross-sectional field and questionnaire data, demographic information, past medical history, and other relevant data were collected. Blood samples were collected for pepsinogen (PG)I, PGII, gastrin-17, and Helicobacter pylori antibody testing, and gastroscopy and histopathologic biopsy were performed. Single factor and logistic regression analyses were used to evaluate the correlation between these indicators and GIM, and decision tree models were used to determine the cut-off points between indicators., Results: Of 443 participants enrolled, 87 (19.6%) were diagnosed with GIM. Single factor analysis showed that pepsin indicators (PGI, PGII, and PGI/PGII ratio) and the factors Mandarin as native language, urban residency, hyperlipidemia, and age were associated with GIM. Logistic regression analysis showed that PGI and age were associated with GIM., Conclusions: Age is an important factor for predicting GIM progression; age >60 years increased its risk. Detection of GIM was higher in individuals with PGI levels >127.20 ng/mL, which could be used as a threshold indicating the need to perform gastroscopy and histopathologic biopsy.

Background: Although many studies have evaluated the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients, the results were conflicting. The objective of this study was to compare clinicopathologic characteristics between SRC type and other types, and evaluate its impact on survival outcome., Methods: We retrospectively reviewed clinicopathologic and survival data of 1891 patients who underwent curative resection for GC. All patients were divided into differentiated, undifferentiated and SRC type according to the histological classification. The prognostic differences between different types were compared and clinicopathologic factors were analyzed., Results: SRC histology type had a poorer disease-free survival (DFS) than differentiated type (5-year DFS, 37.7% vs 52.2%, P<0.001), but there was no prognostic difference between SRC type and undifferentiated type (37.7% vs 41.9%, P>0.05). For early GC patients, SRC type was more frequent in younger, female patients and T1a stage tumors; the 5-year DFS of SRC type was similar to that of any other histology type (P>0.05). SRC type showed more aggressive biological features, including extensive stomach involvement, large tumor size, advanced pTstage and pN stage, than other types for locally advanced GC patients; poorer DFS was observed in SRC type compared with differentiated type. Multivariate analysis indicated that SRC type (HR:1.71, 95%CI:1.10-1.68, P<0.01) and undifferentiated type (HR:1.21, 95%CI:1.04-1.40, P<0.05) were independently associated with poor DFS in locally advanced GC patients., Conclusion: There was a significant difference between early and locally advanced GC patients with regard to clinicopathologic features and prognostic significance of SRC histology. SRC type was an independent prognostic factor for locally advanced GC patients, but not for early GC patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To determine clinicopathological features, risk of lymph node metastasis (LNM) and survival outcome in synchronous multiple early gastric cancer (MEGC) patients., Methods: A total of 338 solitary early gastric cancer (SEGC) and 26 MEGC patients who underwent surgical resection were retrospectively reviewed. The clinicopathological features and predictive factors for MEGC patients were evaluated. Also, we analyzed risk factors for LNM and compared survival difference between SEGC and MEGC patients., Results: The frequency of multiple synchronous lesions was 7.1% in early gastric cancer (EGC) patients. The main and minor lesions were mostly confined to the same third of the stomach (84.6%, 22/26), and the most common location was the lower third of the stomach. With regard to the number of coexisting lesions, most of the patients had two lesions and more than three lesions were not common. Tumor size≤2cm (OR:2.684, 95%CI:1.131-6.368, P<0.05) and the presence of atrophic gastritis (OR:2.418, 95%CI:1.052-5.555, P<0.05) were independent risk factors for synchronous MEGC. There was no significant statistical difference between SEGC and MEGC for LNM (17.5% vs 23.1%, P=0.311). The number of coexisting lesions was not associated with the risk of LNM in EGC. In addition, the survival outcome of MEGC patients was similar to that of SEGC (5-year RFS rate, 96.0% vs 93.7%, P=0.329;5-year OS rate, 96.0% vs 88.3%, P=0.479)., Conclusion: Meticulous endoscopic examination at the initial diagnosis of MEGC was very important, especially for those with precancerous lesions such as atrophic gastritis. In terms of treatment methods, endoscopic resection may be equally suitable for synchronous MEGC if the lesions fulfilled its indication criteria., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aims: The prognostic significance of perineural invasion (PNI) for gastric cancer (GC) patients was under debate. This study aimed to review relevant studies and evaluate the impact of PNI on the survival outcome of GC patients., Methods: Systematic literature search was performed using PubMed and Embase databases. The relevant data were extracted, and the association between PNI and clinicopathological characteristics or survival outcome in GC patients were evaluated using a fixed-effect model or random-effect model., Results: A total 13 studies involving 7004 GC patients were included in this meta-analysis. The positive rate of PNI was 35.9% (2512/7004) in GC patients, ranging from 6.9% to 75.6%. There were significant relationships between PNI and a series of unfavourable clinicopathological factors including undifferentiated histology type (OR: 1.78, 95% CI 1.37 to 2.33, p<0.001; I 2 =75.3%), diffuse type (OR: 1.96, 95% CI 1.07 to 3.60, p=0.029; I 2 =79.5%), lymphatic invasion (OR: 7.00, 95% CI 3.76 to 13.03, p<0.001; I 2 =83.6%), vascular invasion (OR: 5.79, 95% CI 1.59 to 21.13, p=0.008; I 2 =95.8%), deeper tumour invasion (OR: 4.79, 95% CI 3.65 to 6.28, p<0.001; I 2 =65.0%) and lymph node metastasis (OR: 3.60, 95% CI 2.37 to 5.47, p<0.001; I 2 =89.6%). In addition, PNI was significantly associated with worse survival outcome in GC patients (HR: 1.69, 95% CI 1.38 to 2.06, p<0.001; I 2 =71.0%)., Conclusion: PNI was frequently detected in surgically resected specimens of GC patients, and it was a predictive factor for survival outcomes in these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The aim of this study was to evaluate the risk factors for proximal resection margin involvement and its impact on survival outcome in patients with proximal gastric cancer., Methods: A total of 488 patients who underwent potentially curative resection for proximal gastric cancer were retrospectively reviewed. Clinicopathological characteristics and survival differences between patients with positive and negative resection margins were compared and prognostic factors were determined by Cox multivariate analysis., Results: In this study, 7.6% (37/488) of patients with proximal gastric cancer had a positive proximal resection margin after postoperative histopathological examination. Positive resection margins were significantly associated with advanced tumour stage and more aggressive biological features including larger tumour size, serosal invasion and lymphovascular invasion. Serosal invasion (OR 4.543, 95% CI 2.201 to 9.380, p<0.001) and lymphovascular invasion (OR 2.279, 95% CI 1.129 to 4.600, p<0.05) were independent risk factors for positive proximal resection margins. In terms of survival outcome, positive resection margins had an adverse impact on the prognosis of patients with proximal gastric cancer (median DFS: 20.7 vs 30.2 months, p<0.001). The multivariate analysis indicated that positive resection margins (HR 1.494, 95% CI 1.042 to 2.142, p=0.029), T stage (T3-T4, HR 2.264, 95% CI 1.484 to 3.454, p<0.001) and N stage (N1-N2 stage, HR 1.696, 95% CI 1.279 to 2.248, p<0.001; N3 stage, HR 2.691, 95% CI 1.967 to 3.681, p<0.001) were independent prognostic factors for patients with proximal gastric cancer., Conclusion: Proximal resection margin involvement was an indicator of more aggressive tumours and an independent prognostic factor for patients with proximal gastric cancer. Aggressive efforts should be made to achieve a negative resection margin if gastric cancer was deemed to be potentially resectable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the prognostic significance of lymphovascular invasion (LVI) for patients with gastric cancer (GC)., Methods: A total of 1,720 consecutive patients who underwent curative gastrectomy were retrospectively identified. The association between LVI and clinicopathologic characteristics was determined and its impact on survival outcome was evaluated., Results: LVI was detected in 21.3% of GC patients, 5.9% of patients with early GC, 24.0% of patients with advanced GC, and 6.7% of node-negative patients using H&E staining. Tumor size (odds ratio [OR], 1.509; 95% confidence interval [CI], 1.159-1.965; P < .01), differentiated type (OR, 1.817; 95% CI, 1.377-2.398; P < .001), and the depth of tumor invasion (OR, 3.011; 95% CI, 2.174-4.171; P < .001) were independent predictive factors for LVI. LVI-positive patients have a poorer prognosis than LVI-negative patients, irrespective of tumor stage or lymph node metastasis. LVI was an independent prognostic factor for patients with GC (hazard ratio, 1.299; 95% CI, 1.112-1.518; P < .001)., Conclusions: LVI provided additional prognostic information for GC patients, and LVI-positive patients should be considered candidates for adjuvant chemotherapy., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Gastric carcinoma is the fourth leading cause of cancer-related morbidity throughout the globe. There are limited clinical therapies for gastric cancer due to lack of effective drugs and ambiguity in molecular mechanisms. As such there is a pressing need for novel and effective anticancer drugs for gastric cancer. The main aim of the current research work was to investigate the anticancer effects of Lanostane natural product in MKN-45 human gastric cancer cells along with evaluating its effects on cell autophagy, apoptosis, and m-TOR/PI3K/AKT signalling pathway., Methods: MTT cytotoxicity assay was used to evaluate cell viability of MKN-45 human gastric cancer cells. Apoptosis was evaluated by fluorescence microscopy using Hoechst 33258 and Annexin-V/propidium iodide (PI) assay using flow cytometry. Autophagy was evaluated by transmission electron microscopy (TEM) and western blot method. Effects on m-TOR/PI3K/AKT related protein expression were evaluated by western blot method., Results: Lanostane molecule led to substantial and dose-dependent growth inhibitory effects onMKN-45 human gastric cancer cells. Clonogenic assay showed significant decrease in MKN-45 cell colonies. Hoechst 33258 and annexin V/PI revealed that lanostane induced dominant apoptotic effects in these cells and exhibited dose-dependence. TEM revealed that lanostane induced autophagy in MKN-45 cells by forming autophagosomes and autophagic vacuoles. Lanostane also targeted m-TOR/PI3K/AKT signalling pathway by altering the expression of some key proteins., Conclusion: Lanostane displayed strong anticancer effects in MKN-45 human gastric cancer cells by triggering apoptosis and autophagy and targeting m-TOR/PI3K/AKT signalling pathway.

Background: Whether Helicobacter pylori eradication could reduce the risk of metachronous gastric cancer remain controversial. In the present study, we performed a systematic review and meta-analysis to evaluate the preventive effect of H. pylori eradication on the occurrence of metachronous gastric cancer after curative endoscopic resection of early gastric cancer., Methods: The related studies were identified by searching PubMed and Embase databases. According to the H. pylori infection status and subsequent treatment, all patients were classified into H. pylori negative group, H. pylori eradication group and noneradication group. The relevant data were extracted and pooled effect size was assessed using a fixed effect model or a random effect model., Results: A total of 11 retrospective cohort studies and 3 randomized controlled trials were included in this meta-analysis. The results based on the cohort studies indicated that the risk of metachronous gastric cancer was significantly lower in H. pylori eradication group than in noneradication group (hazard ratios: 0.65, 95% confidence interval: 0.50-0.86, P=0.002; I=0%). The pooled result of 2 randomized controlled trials demonstrated that the patients receiving anti-H. pylori treatment had a lower risk of metachronous gastric cancer than those who did not receive H. pylori eradication treatment (hazard ratios: 0.43, 95% confidence interval: 0.26-0.70, P=0.001; I=0%). In addition, the occurrence of metachronous gastric cancer in H. pylori eradication group was not significantly different from that in H. pylori negative group., Conclusions: Successful H. pylori eradication may be useful for the prevention of metachronous gastric cancer after curative endoscopic resection of early gastric cancer. Thus, anti-H. pylori treatment should be considered for those patients with H. pylori infection after curative endoscopic resection.

Objectives : To improve the prognostic accuracy of 8th edition of American Joint Committee on Cancer TNM staging system for gastric cancer by reclassifying N3a category. Methods : 1446 patients who underwent R0 surgery for histologically proven gastric cancers with ≥16 lymph nodes retrieved were selected. Results : Significant prognostic difference was observed among patients in N3a category ('7-10' group vs '11-15' group; P = 0.029). We proposed a revised pN category in which patients with '7-10' metastatic lymph nodes were categorized as r-N3a, '11-15' as r-N3b, and '>15' as r-N3c. Prognosis for patients in T2r-N3aM0 was similar to that of patients in T4aN0M0/T3N1M0/T2N2M0/T1r-N3bM0 (P = 0.584), but significantly better than that of patients in T4bN0M0/T4aN1-2M0/T3N2M0/T2r-N3bM0 (P = 0.031). Similarly, prognoses for patients in T3r-N3aM0 and T4ar-N3aM0 were similar to that of patients in T4bN0M0/T4aN1-2M0/T3N2M0/T2r-N3bM0 (P = 0.136; P = 0.193), but significantly better than that of patients in T4bN1-2M0/T4ar-N3bM0/T3r-N3bM0/T1-2r-N3cM0 (P = 0.011; P = 0.017). A revised TNM system was also proposed, in which T2r-N3aM0 was incorporated into stage IIB, T3r-N3aM0 and T4ar-N3aM0 into stage IIIA. The revised TNM system had better homogeneity, discriminatory ability, and monotonicity of gradients than the 8th edition system. Conclusion : Patients with 7-10 metastatic lymph nodes in T2-T4a categories should be considered lower stage in the final TNM stage.

Purpose: Radical gastrectomy with D2 lymphadenectomy has been widely recognized as standard surgical procedure for advanced gastric cancer, while the role of No. 14v lymphadenectomy in distal gastric cancer remains controversial., Methods: Clinicopathological data of 793 distal gastric cancer patients who underwent at least a radical D2 lymphadenectomy with No. 6 nodes metastasis were retrospectively reviewed., Results: Fifty patients received No. 14v lymphadenectomy. Patients with No. 14v nodes metastasis (21/50, 42.0%) had poor prognosis. The No. 14v nodes metastasis was not an independent prognostic factor (P = 0.075). In distal gastric cancer patients with No. 6 nodes metastasis, No. 14v lymphadenectomy deteriorated overall survival, what's more, No. 14v lymphadenectomy was an independent risk prognostic factor (hazard ratio: 1.404; 95% confidence interval 1.043-1.889; P = 0.025). There was no significant difference in overall or locoregional and other types of recurrence rate between the 14vD+ and the 14vD- groups. The proportion of complication rate was greater in 14vD+ group (P = 0.001)., Conclusion: Extended D2 gastrectomy including No. 14v lymphadenectomy seems to be associated with poor overall survival and increased complication rate of distal gastric cancer patients with No. 6 nodes metastasis.

Purpose: By comparing short- and long-term outcomes following totally robotic radical distal gastrectomy (TRDG) and robotic-assisted radical distal gastrectomy (RADG), we aimed to assess in which modus operandi patients will benefit more., Methods: From January 2015 to May 2019, we included 332 patients undergone RADG (237) and TRDG (95). Based on the propensity score matching (PSM), inclusion and exclusion criteria, 246 patients were finally included in the propensity score-matched cohort including RADG group (164) and TRDG group (82). We then compared the short- and long-term outcomes following both groups., Results: Propensity score-matched cohort revealed no significant differences in both groups. Intra-abdominal bleeding, time to pass flatus, postoperative activity time, length of incision hospital stays, and stress response were significantly less in TRDG group than in RADG group. We observed 30 complications in RADG group while 13 complications in TRDG group. There were no significant differences in TRDG group and RADG group in terms of operation time, time for anastomosis, proximal resection, distal resection margin, number of lymph node resection, and total hospitalization cost. Both 3-year overall survival and 3-year disease-free survival were comparable in both groups., Conclusions: TRDG is a safe and feasible modus operandi profiting from short- and long-term outcomes compared with RADG. As surgeons improving their professional skills, TRDG could serve as the standard procedure for distal locally advanced gastric cancer with D2 lymphadenectomy.

Background: Whether intraoperative blood loss (IBL) was independently associated with poor prognosis of gastric cancer (GC) patients remains controversial. In the present study, we evaluated the impact of IBL on the disease-free survival (DFS) of GC patients., Methods: A total of 1669 patients who underwent curative gastrectomy for GC were reviewed retrospectively. All patients were classified as IBL < 400 mL and IBL ≥ 400 mL group according to the amount of IBL. The prognostic difference between two patient groups was compared and clinicopathologic factors associated with the prognosis of GC patients were analyzed., Results: The 5-year DFS rate of the patients with IBL < 400 mL and those with IBL ≥ 400 mL was 52.1% and 41.5%, respectively (P < 0.001). The 5-year DFS rate of the patients who did and did not receive intraoperative blood transfusion was 36.9% and 53.2%, respectively (P < 0.001). However, the similar survival outcomes were not observed in the subgroup analysis based on the TNM stage. The multivariate analysis indicated that IBL (HR 1.021, 95% CI 0.875-1.191, P > 0.05) and intraoperative blood transfusion (HR 1.111, 95% CI 0.943-1.309, P > 0.05) were not independent prognostic factors for GC patients. In addition, the patients with IBL ≥ 400 mL had a higher risk of postoperative complications than those with IBL < 400 mL, especially for intraabdominal infection and wound infection. The tumor located in upper 1/3 stomach, total gastrectomy, combined organ resection and advanced tumor stage (stage III) were independent risk factors for intraoperative massive hemorrhage., Conclusion: Intraoperative blood loss was significantly associated with tumor-related and surgery-related factors. Intraoperative blood loss itself could not independently affect survival outcome of GC patients after curative gastrectomy.

Background: Recently, increased evidence indicated that additional surgery should be performed in highly selected patients with non-curative endoscopic resection. In this study, we performed a systematic review and meta-analysis to evaluate the risk factors associated with lymph node metastasis for the patients with non-curative endoscopic resection of early gastric cancer., Methods: The related studies were identified by searching PubMed and Embase databases. According to the status of lymph node metastasis, all patients were classified into node-negative group and node-positive group. The relevant clinicopathologic factors were extracted, and the pooled odds ratio (OR) and 95% confidence interval (CIs) were assessed using a fixed effects model or random effects model., Results: A total of nine relevant studies involving 1720 early gastric cancer patients who underwent additional surgery following the non-curative endoscopic resection were included in this meta-analysis. The results indicated that deeper submucosal invasion (SM2) (OR 3.44, 95% CI 1.94-6.10, P < 0.001; I 2  = 0%), positive vertical margin (OR 2.35, 95% CI 1.57-3.53, P < 0.001; I 2  = 0%), lymphatic invasion (OR 11.06, 95% CI 5.47-22.36, P < 0.001; I 2  = 0%), and vascular invasion (OR 2.79, 95% CI 1.68-4.64, P < 0.001; I 2  = 0%) were significantly associated with lymph node metastasis for these patients. However, horizontal margin, tumor size, differentiation type, and ulceration were not identified as risk factors associated with lymph node metastasis., Conclusion: Lymphatic invasion, vascular invasion, deeper submucosal invasion (SM2), and positive vertical margin should be strongly considered in selecting the candidates for additional surgery treatment.

Purpose: Skip metastasis (SK) is an exceptional pattern of lymph node metastasis and the incidence of skip metastasis is not infrequent in gastric cancer (GC). In the present study, we evaluated the clinical significance of skip LN metastasis in GC patients., Methods: According to the anatomical location of positive lymph nodes (LNs), the patients who underwent curative gastrectomy in our institute were classified in three groups: only perigastric involvement (PG group), only extraperigastric involvement (SK group) and both perigastric and extraperigastric involvement (PG+EP group). The clinicopathologic features and prognostic differences between the different groups were compared., Results: The incidence of skip metastasis was 3.9% in all GC patients and the most common location of skip metastasis was No.7 and No.8a node station. The proportion of only one involved station accounted for 83.0% of all cases. In addition, the SK group had fewer numbers of retrieved LNs than the PG and the PG+EP group, especially in the perigastric area. There were significant differences between different groups in the baseline characteristics. After clinicopathologic factors were adjusted and matched, we found that the prognosis of skip metastasis was poorer than that of only perigastric involvement, but was similar to that of both perigastric and extraperigastric involvement., Conclusion: The patients with skip metastasis had a poorer prognosis than those with only perigastric involvement. Anatomical location of metastatic LNs may be not ignored, and adequate lymphadenectomy should be indispensable for node-positive patients.

Aims: The prognostic significance of infiltration growth pattern (INF) in patients with gastric cancer (GC) remains controversial. In the present study, we evaluated the impact of INF pattern on the prognosis of patients with advanced GC., Methods: A total of 1455 patients with advanced GC who underwent curative gastrectomy in our institution were retrospectively analysed. All patients were histopathologically classified as INFa/b and INFc pattern according to the Japanese Classification of Gastric Cancer. The prognostic difference between two patterns was compared and clinicopathological features were analysed., Results: The prognosis of the patients with INFc pattern was poorer than that of those with INFa/b pattern (5-year disease-free survival, INFa/b: 48.4% vs INFc: 33.5%, p < 0.001), even when they were stratified according to lymph node metastasis and the tumour, node, metastases stage. In addition, the subgroup analysis indicated that INFc pattern was significantly associated with poorer prognosis of T2-T3 stage patients (T2, INFa/b: 72.7% vs INFc: 55.4%; T3, INFa/b: 47.4% vs INFc: 33.5%; p<0.001). However, a similar result was not observed among T4a stage patients (INFa/b: 26.8% vs INFc: 24.8%, p>0.05). The prognosis of T2 stage patients with INFc pattern was similar to that of T3 stage patients with INFa/b pattern (p>0.05). Also, there was no significantly prognostic difference between T3 stage patients with INFc pattern and T4a stage patients (p>0.05). The multivariate analysis indicated that INF pattern was an independent prognostic factor for patients with advanced GC (HR 1.259, 95%CI 1.089 to 1.454)., Conclusion: In view of its prognostic significance, histopathological evaluation of INF pattern in surgically resected specimens should be recommended in patients with advanced GC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: despite a better prognosis in node-negative advanced gastric cancer (GC), a proportion of patients have a tumor recurrence within five years and eventually die due to cancer-related causes. The present study aimed to evaluate the predictive factors of tumor recurrence and long-term survival in node-negative advanced GC., Methods: a total of 646 node-negative advanced GC patients who underwent a curative gastrectomy in our institution were included in the study. The impact of different clinicopathologic factors on tumor recurrence and overall survival were analyzed., Results: tumor recurrences were observed in 181 patients and the cumulative recurrence rate at two-years and five-years were 50.8% and 86.2%, respectively. Lymphovascular invasion, advanced T stage (T3-T4) and an inadequate number of retrieved lymph nodes (LNs) were independent predictive factors of tumor recurrence in node-negative advanced GC. Older age, an upper 1/3 tumor, lymphovascular invasion, infiltration growth pattern (INFγ) and the depth of tumor invasion (T4 stage) were independently associated with long-term survival. With regard to node-negative patients with ≥ 15 retrieved LNs, infiltration growth pattern (INFγ) and advanced T stage (T3-T4) were independent risk factors for both tumor recurrence and long-term survival., Conclusion: in addition to lymphovascular invasion, inadequate RLNs and advanced T stage, the prognostic significance of infiltration growth pattern in node-negative advanced GC was especially emphasized. These risk factors should be considered when selecting candidates for adjuvant chemotherapy and postoperative surveillance.

Background: Whether high body mass index (BMI) was associated with increased postoperative complications and unfavorable prognosis of gastric cancer (GC) patients remain controversial. In the present study, we performed a systematic review and meta-analysis to evaluate the impact of high BMI on surgical outcome, postoperative complications and long-term survival of GC patients., Methods: The related studies were identified by searching PubMed and Embase databases. According to the BMI, all GC patients were classified into BMI ≥25 kg/m 2 group and BMI <25 kg/m 2 group. The relevant data was extracted and pooled effect size was assessed using a fixed effect model or random effect model., Results: A total of 36 relevant studies involving 30,642 GC patients were included in this meta-analysis. The results indicated that high BMI patients had longer operation time, fewer number of retrieved lymph nodes and larger amount of intraoperative blood loss than other patients, regardless of open gastrectomy or laparoscopic gastrectomy. In addition, the risk of postoperative complications was significantly higher in the patients with BMI ≥25 kg/m 2 than in those with BMI <25 kg/m 2 , especially for infectious complications. However, high BMI had no negative impact on postoperative mortality and long-term survival of GC patients., Conclusion: Despite the increased surgical difficulty and postoperative complications, high BMI was not associated with the prognosis of GC patients. To reduce the risk of postoperative complications, more meticulous operation technique and improved perioperative management should be necessary for high BMI patients., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aim: To investigate whether the 8th edition of Tumor, Node, Metastasis (TNM) staging could properly evaluate the prognosis of gastric cancer patients., Methods: The prognostic performance between the 7th and 8th edition of TNM staging was compared and clinicopathologic features were analyzed., Results: The stage shifts in the 8th edition staging resulted in the increased numbers of stage IIIA patients and decreased numbers of stage IIB, stage IIIB and stage IIIC patients. Compared with the previous edition, the 8th edition of TNM staging provided a better prognostic stratification for stage III patients. However, whether it is reasonable to incorporate T4aN2, T4aN3a and T4bN3b into stage IIIA, stage IIIB and stage IIIC respectively, which still need further validation., Conclusion: Despite the obvious superiority, several deficiencies may still exist in the new edition staging. To better provide prognostic information and therapeutic guidance for gastric cancer patients, the TNM staging system should be further improved in the future.

Objective: In this study, we performed a systematic review and meta-analysis to evaluate the impact of preoperative underweight status on postoperative complications and survival outcome of gastric cancer (GC) patients., Methods: The related studies were identified by searching PubMed and Embase databases. According to the body mass index (BMI), all patients were classified into underweight group (<18.5 kg/m 2 ) and normal weight group (≥18.5 kg/m 2 , <25 kg/m 2 ). The relevant data were extracted and pooled effect size were assessed using a fixed effect model or random effect model., Results: A total of 12 studies were included in this meta-analysis. The results indicated that underweight patients had a higher risk of postoperative complications than normal weight patients (RR: 1.28, 95% CI: 1.01-1.61, P < 0.05; I 2 = 57.3%), especially for pulmonary infection (RR: 1.58, 95% CI: 1.03-2.43, P < 0.05; I 2 = 47.7%). However, there was no significant difference between underweight and normal weight patients for major surgery-related complications such as anastomotic leakage, wound infection, and intra-abdominal infection. In addition, the short-term (RR: 2.12, 95% CI: 1.47-3.06, P < 0.001; I 2 = 0%) and long-term survival (HR: 1.53, 95% CI: 1.14-2.07, P < 0.01; I 2 = 64.0%) of underweight patients was significantly poorer than that of normal weight patients., Conclusion: Preoperative underweight status was significantly associated with unfavorable postoperative outcome of GC patients. The status may represent excessive nutritional consumption and malnutrition resulting from aggressive tumor.

BRCA1-associated protein 1 (BAP1) has been reported as a novel tumor suppressor, while in gastric adenocarcinoma, the function of this protein was still await to be uncovered. Based on a large group of patients with gastric adenocarcinoma, our study aimed to have a further understanding about the correlation of BAP1 expression and patients' clinical outcomes. We performed quantitative PCR and Western blot to examine BAP1 expression in 38 cases of gastric adenocarcinoma samples and adjacent non-cancerous tissues. Immunochemistry was used to evaluate BAP1 expression in a large cohort of 474 paraffin-embedded specimens. The clinical and prognostic significance of BAP1 expression was statistically analyzed. Postoperative survival between groups was using Kaplan-Meier analysis. BAP1 was overexpressed in paracancerous normal mucosa compared with gastric cancer. Decreased BAP1 expression was associated with higher histologic grade (P = 0.044), tumor infiltration (P < 0.001), metastasis status (P = 0.023), and TNM stage (P < 0.001). Patients with low expression of BAP1 had shorter overall survival compared with those with high expression (P < 0.001). Patients' survival in stage N0 could be stratified by the expression of BAP1. Multivariate analysis showed that in gastric adenocarcinoma, BAP1 expressing level was an independent prognostic factor (RR = 0.575, P < 0.001). Decreased expression of BAP1 suggests pessimistic prognosis for gastric adenocarcinoma patients. Further studies are warranted.

Objective: To compare the long-term survival of total laparoscopic radical distal gastrectomy (TLDG) with delta-shaped anastomosis and laparoscopic assisted radical distal gastrectomy (LADG) with tubular anastomosis., Methods: The study retrospectively analyzed the clinical and pathologic data of 160 distal gastric cancer patients who underwent laparoscopic radical distal gastrectomy with Billroth I anastomosis at the First Affiliated Hospital of Chongqing Medical University from December 2012 to March 2015. All the patients were definitively diagnosed as primary gastric carcinoma before operation, and no evidences of invasion to adjacent organs, distant metastasis or enlarged fused lymph nodes around important vessels were discovered by image tests. Eighty-six patients underwent TLDG with delta-shaped anastomosis (delta-shaped anastomosis group, DSG) and 74 patients underwent LADG with tubular anastomosis (tubular anastomosis group, TAG) in two surgery teams who had different experience of gastroduodenostomy. All the patients agreed the operation and signed informed consent. All patients followed until October 2015 when the final cumulative survival rate was counted. Survival was analyzed by Kaplan-Meier method., Results: The baseline data were comparable and operations were successfully completed. Postoperative follow-up time of DSG was 7-32 months, follow-up rate was 91%(78/86), and 11 of whom died of the gastric cancer. The cumulative survival rate by the end of the follow-up was 82.8%. Postoperative follow-up time of TAG was 7-33 months, follow-up rate was 95%(70/74), 7 of whom died of the gastric cancer. The cumulative survival rate by the end of the follow-up was 81.7%. The intergroup difference of cumulative survival rate was not significant(χ(2)=1.210, P=0.271). No stage I patient died of gastric cancer in both groups. The cumulative survival rate by the end of the follow-up of stage II was 87.2% vs. 93.3%(DAG vs. TAG, χ(2)=0.426, P=0.514) ,and in stage III was 65.3% vs. 37.6%(DAG vs. TAG, χ(2)=0.718, P=0.397), and the differences were not significant., Conclusion: The TLDG with delta-shaped anastomosis and LADG with tubular anastomosis have similar long-term survival for distal gastric cancer treatment.

Gastric cancer remains high prevalence and fatality rates in China even though its morbidity has been decreased drastically. Allicin, which is from an assistance food-garlic (Allium Sativum L), was found to be effective in gastric cancer treatment. It is a defensive substance with a board biological properties: inhibition of bacteria, fungus, virus, controlled hypertension, diabetes, and chemoprevention of several cancers, etc. Experiments have shown that allicin can be chemopreventive to gastric cancer by inhibiting the growth of cancer cells, arresting cell cycle at G2/M phase, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, which includes the caspase-dependent/-independent pathways and death receptor pathway. Those mechanisms probably involve in modulating enzymatic activity, restraining DNA formation, scavenging free radicals, and affecting cell proliferation and even tumor growth. Therefore, this review is focus on the mechanism of allicin in gastric cancer.

Objective: This study sought to investigate the role of the forkhead transcription factor FOXO3a in the prognosis of stage II/III gastric cancer patients., Materials and Methods: A single-institution cohort of 289 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor and adjacent normal specimens were used for tissue microarray construction. Tissue sections were immunostained with FOXO3a. Microscopic evaluation to assess the presence and localization of FOXO3a in tumor and adjacent normal tissues was performed. Results were analyzed for association with clinicopathological characters and overall survival (OS)., Results: FOXO3a expression was significantly higher in tumor tissues compared with adjacent normal tissues, and nuclear FOXO3a staining was observed to be more common in tumor samples than adjacent normal tissues. Poorer prognosis was seen in patients with tumors harboring lower expression of FOXO3a and also patients with adjacent normal tissues harboring higher expression of FOXO3a. High expression of FOXO3a in tumor tissues served as a good prognostic marker with multivariate hazard ratio (HR) of 0.737 (95% CI, 0.574 to 0.947; P=0.017) for OS., Conclusion: The expression of FOXO3a was upregulated and activated in gastric cancer tissues, and was significantly associated with a favorable prognosis in stage II/III gastric cancer patients.

Cellular movement is mainly orchestrated by actin-dependent cytoskeleton in which Rho GTPase Rac1 or vasodilator-stimulated phosphoprotein (VASP) closely collaborates. In the present in vitro study, we investigated the inhibitory effect and underlying molecular mechanism of icariin, a pure extract of the traditional Chinese medicine Herba epimedii, on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Rac1-siRNA-dependent down-regulation of Rac1 led to a large drop in VASP expression, whereas VASP-siRNA led to a slight fall in Rac1 expression, implying that the amount of Rac1 may influence VASP expression level. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP. These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug.

Objective: To study the relationship between consumption of fish sauce, diet, living-habit and risk of gastric cancer., Methods: A population-based 1:2 matched case-control study was conducted in Changle and Fuqing Cities of Fujian Province during May 1994 to July 1995. Totally, 272 matched pairs were investigated., Results: Risk state single-factor analysis indicated that there were significant associations between occurrence of gastric cancer and over consumption of fish sauce (OR = 2.57), pickled vegetables (OR = 1.41) and sea food (OR = 1.57), low consumption of fresh vegetables (OR = 1.95), citrus fruits (OR = 1.41), other fruits (OR = 1.31) and green tea (OR = 1.72), exposure to moldy cereals (OR = 2.32), taking meals at irregular times (OR = 5.47) and familial history of malignancy (OR = 3.27). No associations between risk of gastric cancer and smoking, alcohol drinking, amount of salft consumption, use of refrigerator were found. Analysis of risk state conditional logistic regression showed that fish sauce, pickled sea food, irregularly taking meals and familial history of malignancy were included in a set of risk factors for gastric cancer, with a summary attributable risk percentage of 75.49%., Conclusion: Over consumption of fish sauce, pickled food, moldy cereals, irregularly taking meals and familial history of malignancy may be the local risk factors for high occurrence of gastric cancer, and fresh vegetables and fruits, green tea may have protective effects on it.