The recurrence of gastric cancer after curative resection had adverse effects on patients’ survival. The treatment presence varied from different countries. The aims of this study were to understand the recurrence incidence, patterns, and timing and to explore the risk factors in China. One thousand three hundred four patients who undergoing curative resection from more than 100 hospitals between January 1st 1986 and September 1st 2013, were surveyed in detail. Clinical pathological factors were examined as potential risk factors of each recurrence pattern using univariate and multivariate analyses. Recurrence timing was also analyzed based on disease-free survival. Among 1304 gastric cancer patients, 793 patients (60.8%) experienced recurrence and 554 patients (42.5%) experienced recurrence within 2 years after operation. The median disease-free survival was 29.00 months (interquartile range [IQR] 12.07, 147.23). Receiving operation in general hospitals was one of independent risk factors of local-regional recurrence (OR = 1.724, 95% CI 1.312 to 2.265) and distant metastasis (OR = 1.496, 95% CI 1.164 to 1.940). Patients would suffer lower risk of distant metastasis if they received no more than 3 cycles adjuvant chemotherapy (OR = 0.640, 95% CI 0.433 to 0.943). Adjuvant radiotherapy could reduce the risk of recurrence (OR 0.259, 95% CI 0.100 to 0.670), especially distant metastasis (OR = 0.260, 95% CI 0.083 to 0.816). More than 60% patients experienced recurrence after curative resection for gastric cancer, especially within 2 years after surgery. Risk factors were clarified between various recurrence patterns. Advanced gastric cancer and undergoing operation in general hospitals contributed to increased recurrence risk and worse survival. Enough number of lymph nodes harvest and standard D2 lymphadenectomy could reduce recurrence. Chinese patients would benefit from adjuvant chemotherapy and radiotherapy.

Gastrointestinal (GI) cancers represent a major public health problem worldwide. Due to the late detection and high heterogeneity of GI cancers, traditional treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy, have shown limited effects, and the overall prognosis of these patients remains poor. Recently, immunotherapy, involving programmed cell death-1 (PD-1) and its ligand (PD-L1), has shown promising efficacy in several solid cancers and seems to have become a potential treatment option for GI cancers This review focuses on data on the development of immunotherapy-based clinical trials in esophageal cancer, gastric cancer, and colorectal cancer. The predictive biomarkers and combination strategies in clinical trials and translational medicine are also discussed. Finally, prospects for immunotherapy in the treatment of GI cancers are described. Although only a small proportion of patients with GI cancers respond to PD-1/PD-L1 blockade, we strongly believe that precision immunotherapy might improve the overall survival of many more GI cancer patients in the future.

Background: Platinum‐based chemotherapy is recommended for the treatment of advanced gastroenteropancreatic neuroendocrine carcinoma (GEP‐NEC). The objective of the current phase 2 study was to compare the efficacy and toxicity between etoposide and cisplatin (EP) and irinotecan and cisplatin (IP) as first‐line treatment in patients with advanced GEP‐NEC.Methods: Patients with advanced, poorly differentiated GEP‐NEC randomly were assigned to receive EP or IP. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression‐free survival, overall survival, and toxicities.Results: The planned size of the study population was 144 patients, but enrollment was terminated early at 66 patients because the premature analysis found similar responses in the 2 treatment arms. The ORRs of the EP and IP arms both were 42.4% (14 of 33 patients). The efficacy was similar for small cell NEC with EP or IP (63.2% and 61.5%, respectively; P = .61), whereas that of IP was slightly better in patients with non–small cell NEC (30% vs 14.3%; P = .42). The median progression‐free survival was 6.4 months and 5.8 months, respectively, for the EP and IP arms (P = .81), and the median overall survival was 11.3 months and 10.2 months, respectively, for the EP and IP arms (P = .37). The incidence of grade 3/4 neutropenia was significantly higher in the EP arm compared with the IP arm (45.4% vs 12.1%; P = .002). Nonhematological toxicity was relatively mild and more frequent in the IP arm compared with the EP arm (54.5% vs 18.2%; P = .001). No toxicity‐related deaths were reported.Conclusions: The results of the current study demonstrated that IP is not inferior to EP, with comparable efficacy for poorly differentiated NEC of the digestive system. In addition, both regimens appear to be well tolerated with diverse toxicity profiles.

The application of immunotherapy in gastrointestinal (GI) cancers remains challenging because of the limited response rate and emerging therapeutic resistance. Combining clinical cohorts, multi‐omics study, and functional/molecular experiments, it is found that ANO1 amplification or high‐expression predicts poor outcomes and resistance to immunotherapy for GI cancer patients. Knocking‐down or inhibiting ANO1 suppresses the growth/metastasis/invasion of multiple GI cancer cell lines, cell‐derived xenograft, and patient‐derived xenograft models. ANO1 contributes to an immune‐suppressive tumor microenvironment and induces acquired resistance to anti‐PD‐1 immunotherapy, while ANO1 knockdown or inhibition enhances immunotherapeutic effectiveness and overcomes resistance to immunotherapy. Mechanistically, through inhibiting cancer ferroptosis in a PI3K‐Akt signaling‐dependent manner, ANO1 enhances tumor progression and facilitates cancer‐associated fibroblast recruitment by promoting TGF‐β release, thus crippling CD8⁺ T cell‐mediated anti‐tumor immunity and generating resistance to immunotherapy. This work highlights ANO1's role in mediating tumor immune microenvironment remodeling and immunotherapeutic resistance, and introduces ANO1 as a promising target for GI cancers’ precision treatment.