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Background: The clinicopathological features and endoscopic characteristics under magnifying endoscopy with narrow band imaging (ME-NBI) between early-stage gastric-type differentiated adenocarcinoma (GDA) and intestinal-type differentiated adenocarcinoma (IDA) remain controversial. Methods: Early gastric adenocarcinomas that underwent endoscopic submucosal dissection (ESD) in Nanjing Drum Tower Hospital between August 2017 and August 2021 were included in the present study. GDA cases and IDA cases were selected based on morphology and immunohistochemistry staining of CD10, MUC2, MUC5AC, and MUC6. Clinicopathological data and endoscopic findings in ME-NBI were compared between GDAs and IDAs. Results: The mucin phenotypes of 657 gastric cancers were gastric (n = 307), intestinal (n = 109), mixed (n = 181) and unclassified (n = 60). No significant difference was observed in terms of gender, age, tumor size, gross type, tumor location, background mucosa, lymphatic invasion, and vascular invasion between patients with GDA and IDA. GDA cases were associated with deeper invasion than IDA cases (p = 0.007). In ME-NBI, GDAs were more likely to exhibit an intralobular loop patten, whereas IDAs were more likely to exhibit a fine network pattern. In addition, the proportion of none-curative resection in GDAs was significantly higher than that in IDAs (p = 0.007). Conclusion: The mucin phenotype of differentiated early gastric adenocarcinoma has clinical significance. GDA was associated with less endoscopically resectability than IDA. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) has been accepted as a standard treatment for early gastric cardiac cancer (EGCC). Here, we investigate the clinical outcomes of the EGCC patients who underwent ESD in different indications.Methods: From January 2011 to October 2019, we enrolled 502 EGCC lesions from 495 patients which were resected by ESD at our center. We retrospectively analyzed the short-term and long-term clinical outcomes among different indication groups.Results: The number of the patients in the absolute indication (AI), expanded indication (EI) and beyond the expanded indication (BEI) groups was 265, 137 and 93, respectively. The en bloc resection rate was 100%, 100% and 98.9% (P = 0.185). The complete resection rate was 99.3%, 98.5% and 74.5%, respectively (P < 0.001). During a median follow-up of 48.1 months, the lymph node metastasis rate was 0%, 0% and 2.3% (P < 0.001). The distant metastasis rate was 0.4%, 0% and 2.3% (P = 0.150). The five-year disease-specific survival rate in the BEI group was 96.6% (P = 0.016), compared to 99.6% in the AI group and 100% in the EI group.Conclusion: The efficacy for ESD patients in EI group was almost equal to the AI group. Patients in the BEI group showed generally favorable clinical outcomes and needed to be carefully checked after ESD. ESD may be an optional treatment for patients unsuitable for gastrectomy. [ABSTRACT FROM AUTHOR]

Aims: Early gastric cardiac cancer (EGCC) has a low risk of lymph node metastasis with the potential for endoscopic therapy. We aimed to evaluate the short- and long-term outcomes of endoscopic submucosal dissection (ESD)-resected EGCCs in a large cohort of Chinese patients and compare endoscopic and clinicopathologic features between EGCC and early gastric non-cardiac cancer (EGNC). Methods: We retrospectively studied 512 EGCCs in 499 consecutive patients and 621 EGNCs in 555 consecutive patients between January 2011 and March 2018 at our center. We investigated clinicopathological characteristics of EGCC tumors, ESD treatment results, adverse events, and postresection patient survival. Results: Compared with EGNC patients, EGCC patients were significantly older (average age: 66 years versus 62 years, p < 0.001). The percentage of the gross 0–IIc pattern was higher in EGCCs (46.1%) than in EGNCs (41.5%), while the frequency of the 0–IIa pattern was lower in EGCCs (14.9%) than in EGNCs (22.4%) (p = 0.001). Compared with EGNCs, EGCCs showed smaller size, deeper invasion, fewer ulcerated or poorly differentiated tumors, but more cases with gastritis cystica profunda. The prevalence of ESD-related complications was higher in EGCCs (6.1%) than in EGNCs (2.3%) (p = 0.001). In EGCCs, the disease-specific survival rate was significantly higher in patients of the noncurative resection group with surgery (100%), compared with that (93.9%) without surgery (p < 0.001). Conclusion: Clinicopathological characteristics were significantly different between EGCCs and EGNCs. ESD is a safe and effective treatment option with favorable outcomes for patients with EGCC. Additional surgery improved survival in patients with noncurative ESD resection. [ABSTRACT FROM AUTHOR]

Gastric cancer prognoses are persistently poor due to cancer's penchant to metastasize. As a crucial regulator of signal transducer and activator of transcription (STAT3) signaling, sirtuin 1's (SIRT1) function in gastric cancer has not been well understood. Here, we report upregulated expression of SIRT1 in tissues isolated from gastric cancer patients. However, we show that the depletion of SIRT1‐mediated enhanced cancer cell proliferation and metastasis, and resulted in the enrichment of phosphorylated STAT3, acetylated STAT3, and matrix metalloproteinase 13 (MMP‐13) in both in vivo and in vitro experiments. Additionally, we demonstrate that small interfering RNAs targeting the production of STAT3, AG490, and CL‐821983 in cancer cells depleted of SIRT1 reduce metastasis. Our findings indicate that MMP‐13 expression is associated with lymph node metastasis and poor survival outcomes in gastric cancer patients. In vivo models also showed that depleted SIRT1 promoted gastric cancer growth via the STAT3/MMP‐13 axis. In conclusion, SIRT1 depletion encourages gastric cancer progression through the activation of STAT3/MMP‐13 signaling, suggesting that SIRT1 may function as a tumor suppressor. We postulate that the upregulation of SIRT1 in gastric cancer patients may be the result of a feedback mechanism that aims to oppose the damaging effects of STAT3 signaling. As such, SIRT1 activators could potentially serve as preventive and therapeutic treatments for metastatic gastric cancer. [ABSTRACT FROM AUTHOR]

Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC. [ABSTRACT FROM AUTHOR]

Background and Aim: Endoscopic ultrasonography (EUS) is a widely used imaging modality for detecting the depth of early gastric cancer (EGC) invasion. However, the studies pertaining to EUS for staging early gastric cancer have reported widely varied sensitivities and specificities. This study was conducted to estimate the overall diagnostic accuracy of EUS for staging the depth in EGCs. Methods: The literatures were identified by searching in PubMed, Embase, and Web of Knowledge databases. Two reviewers independently extracted the information from the literatures for constructing 2 × 2 table. A random-effect model or a fixed-effect model was used to estimate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. A summary receiver operating characteristic curve also was constructed. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. Results: The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of EUS for M staging were 76% (95% confidence interval [CI], 74-78%), 72% (95% CI, 69-75%), 3.67 (95% CI, 2.48-5.44), and 0.31 (95% CI, 0.24-0.40), respectively. For SM staging, these results were 62% (95% CI, 59-66%), 78% (95% CI, 76-80%), 2.99 (95% CI, 2.26-3.96), and 0.43 (95% CI, 0.32-0.57), respectively. For M/SM1 staging, they were 90% (95% CI, 88-92%), 67% (95% CI, 61-72%), 3.14 (95% CI, 2.08-4.73), and 0.12 (95% CI, 0.07-0.22), respectively. The area under the curve for mucosal, submucosal, and mucosal/minimal submucosal invasion staging were 0.85, 0.82, and 0.81, respectively. Conclusions: Endoscopic ultrasonography only has a relatively low accuracy for staging the depth of invasion in EGCs. Accordingly, EUS may be not indispensable in the staging of EGCs. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that STAT3 signaling plays important roles in regulating epigenetic aberrance during tumorigenesis, especially in the expression of certain key epigenetic enzymes such as DNMTs, HDACs, and HMTs. However, there has been no report on the relationship of STAT3 signaling and epigenetic aberrance in gastrocarcinogenesis. Aim: The purpose of this study was to explore the interrelationship of STAT3 signaling pathway and epigenetic aberrance in gastrocarcinogenesis. Methods: Immunohistochemistry was utilized to examine the protein expressions of pSTAT3, DNMT1, HDAC1, and EZH2 in 153 tissue specimens, including 20 of normal gastric epithelium tissue, 21 of intestinal metaplasia (IM), 24 of dysplasia (DYS), 23 of early gastric cancer (EGC) and 65 of advanced gastric cancer (AGC), and then analyze their possible relationship with clinicopathological factors. Results: We found that the four protein expressions were obviously enhanced following the malignant process of gastric carcinogenesis. Pearson correlation analysis of all the pathological groups showed that expression of pSTAT3 was highly associated with DNMT1, but not with HADC1 and EZH2. However, significant correlations were detected among the expression of DNMT1, HDAC1, and EZH2. Further analysis of each pathological group demonstrated that pSTAT3's expression was dramatically related with DNTM1 in the IM ( P = 0.021) and EGC groups ( P = 0.013) and correlated with EZH2 in the DYS group ( P = 0.020). Furthermore, pSTAT3's expression was associated with T staging ( P = 0.015) in the AGC group, whereas DNMT1 was associated with gender ( P = 0.021), HDAC1 with Lauren classification ( P = 0.007), and EZH2 with T staging ( P = 0.003) and lymphatic staging ( P = 0.038). Conclusions: The STAT3 signaling pathway may correlate with epigenetic aberrance during gastrocarcinogenesis. [ABSTRACT FROM AUTHOR]

The mortality rates of gastric cancer remain high due to limited therapeutic strategies. As a highly selective inhibitor of the BD2 domain of BET family proteins, ABBV-744 has potent chemotherapeutic activity against various human solid tumors. However, whether ABBV-744 has potential anti-tumor effects in gastric cancer remain largely unknown. In this study, we evaluated the effect of ABBV-744 on gastric cancer cells and explored the possible underlying mechanisms. We found that ABBV-744 inhibited the growth of gastric cancer cells and patient-derived tumor organoids in a dose-dependent manner. Cellular experiments revealed that ABBV-744 induced mitochondria damage, reactive oxygen species accumulation, cell cycle arrest and apoptotic cell death in gastric cancer cells. Transcriptomic analysis using RNA-sequencing data identified autophagy as a crucial pathway involved in the cell death caused by ABBV-744. Mechanically, further studies showed that ABBV-744 induced autophagy flux in gastric cancer cells by inactivating PI3K/AKT/mTOR/p70S6k and activating the MAPK signaling pathways. In vivo mouse xenograft studies demonstrated that ABBV-744 significantly suppressed the growth of gastric cancer cells via inducing autophagy. Taken together, our results suggest that ABBV-744 is a novel drug candidate for gastric cancer. [ABSTRACT FROM AUTHOR]