The synergistic effect of neoadjuvant immunotherapy and chemoradiotherapy in gastric adenocarcinoma is unclear. This phase II trial (NCT03631615) investigated this neoadjuvant combination in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Thirty-six patients received capecitabine 850 mg/m² twice daily and simultaneous radiotherapy for 5 weeks, sandwiched by a 21-day cycle of oxaliplatin 130 mg/m² (day 1) plus capecitabine 1000 mg/m² twice daily (days 1–14), respectively, followed by surgery. Camrelizumab 200 mg (day 1) was given for 5 cycles since initiating chemotherapy. Primary endpoint was pathological complete response (pCR, ypT0) rate. Secondary endpoints included total pCR (tpCR, ypT0N0) rate, major pathological response (MPR, < 10% residual tumor cells) rate, margin-free (R0) resection rate, downstaging, progression-free survival (PFS), overall survival (OS), and safety. The pCR rate was 33.3% (95% CI, 18.6–51.0), meeting pre-specified endpoint. TpCR, MPR, and R0 resection rates were 33.3%, 44.4%, and 91.7%, respectively. Twenty-eight (77.8%) patients reached ypN0. Two-year PFS and OS rates were 66.9% and 76.1%, respectively. The most common grade 3–4 adverse event was decreased lymphocyte count (27 [75.0%]). Neoadjuvant camrelizumab plus concurrent chemoradiotherapy exhibits promising pathological response in patients with locally advanced gastric adenocarcinoma, with an acceptable safety profile.

The immune microenvironment plays a critical role in tumor biology. The molecular profiles of immune components and related genes are of tremendous value for the study of primary resistance to immune checkpoint blockers (ICBs) for gastric cancer (GC) and serve as prognostic biomarkers to predict GC survival. Recent studies have revealed that tumor immune cell infiltration (ICI) is an indicator of the survival and responsiveness to chemotherapy in GC patients. Here, we describe the immune cell landscape based on the ESTIMATE and CIBERSORT algorithms to help separate GC into 3 ICI clusters using the unsupervised clustering method. Further in-depth analyses, such as differential expression gene (DEG) analysis and principal component analysis (PCA), help to establish an ICI scoring system. A low ICI score is characterized by an increased tumor mutation burden (TMB). The combination of the ICI score and TMB score better predicts the survival of GC patients. Analyses based on public and our own database revealed that the ICI scoring system could also help predict the survival and chemotherapy responsiveness of GC patients. The present study demonstrated that the ICI score may be an effective prognostic biomarker and predictive indicator for chemotherapy and immunotherapy.

Background: Digital histopathology provides valuable information for clinical decision-making. We hypothesized that a deep risk network (DeepRisk) based on digital pathology signature (DPS) derived from whole-slide images could improve the prognostic value of the tumor, node, and metastasis (TNM) staging system and offer chemotherapeutic benefits for gastric cancer (GC). Methods: DeepRisk is a multi-scale, attention-based learning model developed on 1120 GCs in the Zhongshan dataset and validated with two external datasets. Then, we assessed its association with prognosis and treatment response. The multi-omics analysis and multiplex Immunohistochemistry were conducted to evaluate the potential pathogenesis and spatial immune contexture underlying DPS. Results: Multivariate analysis indicated that the DPS was an independent prognosticator with a better C-index (0.84 for overall survival and 0.71 for disease-free survival). Patients with low-DPS after neoadjuvant chemotherapy responded favorably to treatment. Spatial analysis indicated that exhausted immune clusters and increased infiltration of CD11b⁺CD11c⁺ immune cells were present at the invasive margin of high-DPS group. Multi-omics data from the Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) hint at the relevance of DPS to myeloid derived suppressor cells infiltration and immune suppression. Conclusion: DeepRisk network is a reliable tool that enhances prognostic value of TNM staging and aid in precise treatment, providing insights into the underlying pathogenic mechanisms.

This study aimed to evaluate the prognostic value of plasma circulating tumor DNA (ctDNA) level in patients with resectable gastric cancer (GC). A total of 59 patients were prospectively enrolled, with their ctDNA detected and paired tumor tissue collected at various peri‐operative time points. Patients with higher 1‐month post‐operative ctDNA levels demonstrated shorter overall survival status (hazard ratio [HR] = 5.30, p = 0.0022) and a higher risk of recurrence (HR = 3.85, p = 0.011). The model combining ctDNA with conventional serum tumor markers for GC, including carcinoembryonic antigen, carbohydrate antigen 19‐9, and CA72‐4, shows high predictive effectiveness for GC prognosis with an area under the curve of 0.940 (p = 0.002), which is higher than net ctDNA and other models without ctDNA. Patients with lower ctDNA levels were more likely to have positive stromal programmed cell death ligand 1 expression (p = 0.046). Additionally, DCAF4L2 mutation was identified as the crucial gene mutation in ctDNA suggesting poor prognosis of patients with GC. Overall, this study highlights that post‐operative ctDNA can serve as an effective biomarker for prognostic prediction and recurrence surveillance in resectable GC.

Although small-bowel perforation is a life-threatening emergency even after immediate surgical intervention, studies have rarely investigated surgical outcomes due to its relatively low incidence. This study aimed to investigate the outcomes of emergency surgery for patients with small-bowel perforation transferred to the intensive care unit (ICU) and the risk factors for mortality. Consecutive patients with small-bowel perforation who were confirmed via emergency surgery and transferred to the ICU in Zhongshan Hospital, Fudan University (Shanghai, China) between February 2011 and May 2020 were retrospectively analysed. Medical records were reviewed to determine clinical features, laboratory indicators, surgical findings, and pathology. A total of 104 patients were included in this study, among whom 18 (17.3%), 59 (56.7%), and 27 (26.0%) underwent perforation repair, segmental resection with primary anastomosis, and small-bowel ostomy, respectively. Malignant tumours were the leading cause of perforation in these patients (40.4%, 42/104). The overall post-operative complication rate and mortality rates were 74.0% (77/104) and 19.2% (20/104), respectively. Malignant tumour-related perforation (odds ratio [OR], 4.659; 95% confidence interval [CI], 1.269–17.105; P = 0.020) and high post-operative arterial blood-lactate level (OR, 1.479; 95% CI, 1.027–2.131; P = 0.036) were identified as independent risk factors for post-operative mortality in patients with small-bowel perforation transferred to the ICU. Patients with small-bowel perforation who are transferred to the ICU after emergency surgery face a high risk of post-operative complications and mortality. Moreover, those patients with malignant tumour-related perforation and higher post-operative blood-lactate levels have poor prognosis.

Background: The prognostic values of serum cytokines in cancer have not yet been fully determined. The objective of this study was to identify potential biomarkers associated with clinical outcomes in critical gastrointestinal (GI) cancer patients. Methods: A retrospective analysis was performed to quantify serum interleukin (IL)-2, IL-8, tumor necrosis factor-α (TNF-α), procalcitonin (PCT), and C-reactive protein (CRP) for correlation with clinical outcomes in GI cancer patients. The patients were divided into tertiles or quartiles based on the cytokine levels: Q1, Q2, and Q3, or Q1, Q2, Q3, and Q4. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values of the cytokines. Results: Trend analysis showed that IL-2, IL-8, TNF-α, PCT, and CRP levels had significant positive correlations with mortality in GI cancer patients (all P-values were lower than 0.05). The significance was observed in Q3 vs. Q1 in IL-2 (P=0.026), Q3 vs. Q1 in IL-8 (P=0.003), Q2 and Q3 vs. Q1 in TNF-α (P=0.012 and P=0.002, respectively), Q4 vs. Q1 in PCT (P=0.031), Q3 and Q4 vs. Q1 in CRP (P=0.011 and P=0.001, respectively). The area under curve (AUC) of IL-2, IL-8, TNF-α, PCT, and CRP were 0.706, 0.729, 0.743, 0.769, and 0.736, and the optimal cutoff points were determined at 838 U/mL, 46.15 pg/mL, 11.95 pg/mL, 0.77 pg/mL, and 109.38 mg/L, respectively. Under these critical values, the sensitivity was 73.3%, 66.7%, 80.0%, 93.3%, and 86.7%, and the specificity was 64.9%, 72.0%, 60.4%, 61.8%, and 68.9%, respectively. Conclusions: In GI cancer patients, serum IL-2, IL-8, TNF-α, PCT, and CRP levels can provide potential prognostic values for predicting clinical outcomes. The results may facilitate the exploration of cancer-related cytokine networks and development of novel therapy for GI cancer patients.