Solid tumors consist of various types of stromal cells in addition to cancer cells. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and play an essential role in tumor progression and metastasis in a variety of malignancies, including gastric cancer. However, the effects of CAFs on gastric cancer cells' progression and metastasis are not well studied. Here we show that matrix metalloproteinase 11 (MMP11) in exosomes secreted from CAFs can be delivered into gastric cancer cells. Gastric CAFs promote gastric cancer cell migration partially through exosomal MMP11. Moreover, MMP11 is overexpressed in exosomes purified from plasma of gastric cancer patients and tumor tissues and associated with overall survival of gastric patients. We also find that MMP11 is negatively regulated by exosomal miR-139 in the CAFs of gastric cancer. Exosomal miR-139 inhibits tumor growth and metastasis of gastric cancer cells by decreasing the expression of MMP11 in vitro and in vivo. Thus, we propose that exosomal miR-139 derived from gastric CAFs could inhibit the progression and metastasis of gastric cancer by decreasing MMP11 in tumor microenvironment.

Background and aims: Endoscopic resection is increasingly performed for gastric gastrointestinal stromal tumors (GIST). However, the safety and outcomes remain elusive. We aimed in this retrospective study to compare operative complications and prognosis between endoscopically and surgically resected small (≤ 5 cm) GIST tumor groups. Methods: In this single-center retrospective study, we compared demographics, clinical outcomes, and the R0 resection rate between the endoscopy (n =268) and surgery (n =141) groups. Only GIST tumors in size of ≤ 5.0 cm were recruited for this comparison study. Results: Overall, the mean age of patients was 59.0 years (range: 31.0-83.0). The male-female ratio was 0.68. The most common site of GIST was, in the descending order, the gastric fundus (55%), corpus (27.6%), cardia (10.8%), and antrum (6.6%). Compared with the surgery group, GIST tumors in the endoscopy group were significantly smaller (1.69±0.9 cm, vs . 3.20±1.2 cm in the surgery group; P <0.001) in size; postoperative hospital stay was significantly shorter (4.66±1.5 days, vs. 8.11±5.0; P <0.001); post-resection time to first liquid diet was significantly shorter (1.94±1.1 days, vs. 4.63±2.6; P < 0.001); the incidence of operative and post-operative complications was significantly fewer (p < 0.05), and hospital costs were significantly lower (20115.4±5113.5¥, vs. 43378.4±16795.7¥; P < 0.001). The R0 resection rate was significantly lower in the endoscopy (93.3%) than in the surgery (99.3%) groups (P< 0.01). In the endoscopy group, 176 (65.7%) and 69 (25.7%) patients were found to be at very low and low risk of aggressiveness, respectively, in comparison to 27(19.2%) and 86 (61.0%) patients in the surgery group, respectively (P <0.001). Among 409 cases, 50 (12.2%) were found to be at intermediate or high risk of aggressiveness, 20 of which were treated with adjuvant imatinib therapy and but only 8/20 taking imatinib for 1 to 3 months because of side effects and high costs. No local or distant tumor recurrence was observed over an average of 33.5-month follow-ups. Two patients died of other disease in the surgery group. Conclusions: Endoscopic resection of selected small gastric GISTs (≤ 5cm) was feasible, safe, and associated with better intraoperative results and an equal postoperative course, compared to surgical resection.

Background : Early gastric carcinoma (EGC) with pure signet ring cell carcinoma (pSRCC) has been reported to have favourable prognosis and low risk of lymph node metastasis (LNM). However, risk factors of LNM and clinicopathological features for early gastric mixed signet ring cell carcinoma (mSRCC) remain poorly investigated. The aim of this study was to identify risk factors of LNM and compare clinicopathological characteristics and prognosis of early gastric pSRCC with mSRCC. Methods : This retrospective study was conducted at our center between 2005 and 2015 in 796 patients underwent radical gastrectomies combined with lymph node dissections, A total of 160 patients with early gastric SRCC underwent gastrectomies with lymph node dissections were reviewed, in which 79 cases were pSRCC and 81 cases were mSRCC. Risk factors of LNM and clinicopathologic features of these two groups were statistically compared, including age, gender, tumor location, gross pattern, size, invasion depth, lymphovascular invasion (LVI), helicobacter pylori ( Hp ) infection, atrophic gastritis, ulcer finding and LNM. Patients were follow-up for post-resection survival. The 5-year survival and disease-specific survival rate were estimated with the Kaplain-Meier method with a log-rank test and compared between the two groups. Results : Tumor size ( P <0.05), invision depth ( P <0.05) and LVI ( P < 0.0001) were risk factors of LNM, LVI ( P < 0.0001) was independent risk factor of LNM in 160 patients. Univariate analysis reviewed LVI ( P < 0.0001) as the risk factor in the pSRCC group, and the risk factors of LNM in the mSRCC included LVI ( P < 0.0001) and tumor size ( P <0.05). Multivariable analysis revealed two independent risk factors in the mSRCC group: 1) tumor size ( P < 0.05), and 2) LVI ( P < 0.0001). The significant characteristics in two groups included the male gender ( P < 0.0001), gross pattern ( P < 0.05), LVI ( P < 0.01), and Hp infection ( P < 0.01). The difference of LNM rate between expanded indication and out of indication in 160 patients was significant ( P =0.03). The overall 5-year survival rate for early gastric SRCC was 96.3%. There was no significant difference in the overall survival and disease-specific survival between the two groups. Conclusions : Although with similar post-resection survival, the independent risk factors of LNM in the early mSRCC group, compared to those in the early pSRCC group, included large tumor size and LVI. Early gastric mSRCC had more aggressive clinicopathological features than pSRCC.

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.

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.