Background The optimal surgical strategy for adenocarcinoma of oesophagogastric junction (AEG) remains debated, particularly regarding lymphadenectomy extent, gastrectomy type and surgical approach, with real-world prospective evidence being scarce. Objective To map lymph node metastasis (LNM) patterns and assess surgical outcomes in a large multicentre cohort of patients with AEG undergoing radical resection. Design The Chinese League of Adenocarcinoma of Esophagogastric Junction (CLAEG) registry, initiated in 2022 across 44 high-volume Chinese centres, prospectively enrolled AEG patients. This analysis included 2044 radical resections, with LNM assessed by station, stratified by Siewert type and neoadjuvant therapy. Surgical outcomes were compared between total versus proximal gastrectomy and laparoscopic versus open resection. Results Most tumours were Siewert type II (64.6%) or III (33.4%). LNM was substantially higher in abdominal than mediastinal stations; category-1 nodes (metastasis, >10%) comprised stations 1, 2, 3, 4, 7, 8a, 9 and 11p. The LNM rates for mediastinal stations were 2.77% (No. 110), 0.71% (No. 111) and 0.68% (No. 112). Patients who received neoadjuvant therapy had lower LNM rates, indicating nodal downstaging. Among those undergoing gastrectomy, patients who underwent total gastrectomy had a lower postoperative complication rate than those who underwent proximal gastrectomy (14.8% vs 21.0%; p=0.001) and achieved more extensive lymphadenectomy. Compared with open surgery, patients who underwent laparoscopic resection experienced faster postoperative recovery without higher complication rates (16.5% vs 17.3%). No perioperative mortality occurred. Conclusion The CLAEG study shows that abdominal lymphadenectomy should be prioritised in AEG, with neoadjuvant therapy, total gastrectomy and laparoscopy associated with favourable short-term outcomes.

INTRODUCTION:The role of prophylactic ileostomy and its potential to reduce the risk of postoperative complications such as anastomotic leakage remains unclear. METHODS:The PILLAR study (2018-2020, China, 17 centers) prospectively compared prophylactic ileostomy (PI) versus nonprophylactic ileostomy (NPI) in patients undergoing laparoscopic low anterior resection for rectal cancer. The primary endpoint was the anastomotic leakage rate. Secondary endpoints included postoperative complications, leakage management/outcomes, and leakage-associated risk factors. RESULTS:A prospective study was conducted to gather data from 728 patients who underwent laparoscopic low anterior resection for rectal cancer, 192 (26.4%) of whom underwent PI. Seven cases of anastomotic leakage were observed in the PI group (3.6%) and 25 cases were observed in the NPI group (4.7%). Statistical analysis revealed no significant difference in the incidence of anastomotic leakage between the two groups. Moreover, the total complication rates were 17.2% in the PI group and 10.3% in the NPI group (P = 0.012). However, the patients with anastomotic leakage in the NPI group had more severe abdominal infections, as evidenced by the C-reactive protein (CRP) values on postoperative day 5 (184.1 ± 72.2 mg/L and 77.2 ± 17.0 mg/L in the NPI and PI groups, respectively) (P<0.001). Patients' postoperative procalcitonin (PCT) values similarly support this conclusion. Notably, despite this difference in infection severity, there was no statistically significant difference in the treatment or outcomes of patients with anastomotic leakage in either group. Furthermore, male sex and CRP levels on the fifth postoperative day are identified as independent risk factors for anastomotic leakage. CONCLUSIONS:PI may have failed to decrease the incidence of anastomotic leakage in patients who underwent laparoscopic low-anterior resection for rectal cancer. Given the higher complication rate associated with PI, its use as a preventive measure for patients at risk of anastomotic leakage should be carefully considered.

Exosomes, critical mediators within the tumor microenvironment (TME), facilitate intercellular communication by transferring bioactive molecules, including noncoding RNAs (ncRNAs). These extracellular vesicles, secreted by nearly all cell types and detectable in bodily fluids, selectively encapsulate functional ncRNAs, which play pivotal roles in tumorigenesis, progression, and therapeutic resistance. In renal cell carcinoma (RCC), exosomal ncRNAs have emerged as key regulators driving tumor proliferation, metastasis, and immunosuppression through mechanisms such as activation of the MAPK pathway, promotion of epithelial-mesenchymal transition (EMT), and modulation of immune cell polarization. Notably, exosomal ncRNAs contribute to drug resistance by mediating cross-talk between cancer cells and stromal components, including fibroblasts and tumor-associated macrophages (TAMs). Their inherent stability, conferred by protective lipid bilayers, enhances their potential as non-invasive diagnostic and prognostic biomarkers. Specific ncRNAs, such as miR-210 and circSDHC, exhibit differential expression in RCC patient sera and urine, offering high diagnostic accuracy for early detection and metastasis monitoring. Furthermore, targeting exosomal ncRNA biogenesis or their downstream pathways-via engineered exosomes loaded with therapeutic RNAs or inhibitors-represents a promising strategy to overcome resistance and improve treatment efficacy. This review comprehensively delineates the mechanistic roles of exosomal ncRNAs in RCC pathogenesis, highlights their clinical utility as biomarkers, and explores innovative therapeutic approaches to disrupt ncRNA-mediated oncogenic signaling. Advancing our understanding of exosome-ncRNA dynamics may unlock novel precision therapies for RCC, addressing unmet challenges in current clinical management.

Objective: This study aimed to develop and validate a predictive model for postoperative complications in gastrointestinal cancer patients using a large multicenter database, based on machine learning algorithms.Methods: We analyzed the clinicopathological data of 3,926 gastrointestinal cancer patients from the Prevalence of Abdominal Complications After GastroEnterological surgery(PACAGE) database, covering 20 medical centers from December 2018 to December 2020. The predictive performance was evaluated using receiver operating characteristic(ROC) curves and Brier Score.Results: The patients were divided into gastric(2,271 cases) and colorectal cancer(1,655 cases) groups and further divided into training and external validation sets. The overall postoperative complication rates for gastric and colorectal cancer groups were 18.1% and 14.8%, respectively. The most common complication was the intraabdominal infection in both gastric and colorectal cancer groups. In the training set, the Random Forest(RF) model predicted the highest mean area under the curve(AUC) values for overall complications and different types of complications, in both the gastric cancer group and the colorectal cancer group, with similar results obtained in the external validation set. ROC curve analysis showed good predictive performance of the RF model for overall and infectious complications. An application-based clinical tool was developed for easy application in clinical practice.Conclusions: This model demonstrated good predictive performance for overall and infectious complications based on the multi-center database, supporting clinical decision-making and personalized treatment strategies.

Though oncolytic viruses (OVs) hold significant potential for comprehensive treatment of malignant tumors, their systemic administration faces substantial challenges such as insufficient circulation time, inadequate tumor targeting, and spontaneous antiviral immune response of the body, which seriously limits the clinical application of OVs. Herein, we proposed a tumor targeting strategy of tumor cell membrane biomimetic liposomes to encapsulate OVs for intravenous delivery, which enables OVs to target the homotypic tumor lesions and exert their oncolytic effect. On the one hand, this cell membrane biomimetic carrier enhanced the encapsulation of OVs by the hybrid lipid membranes, concealed the viral capsid proteins, and diminished the neutralization and clearance of the virions from the bloodstream. On the other hand, enhanced tumor targeted delivery can be achieved through the utilization of homologous adhesion molecules on the surface of tumor cell membrane. In addition, this strategy also promoted the tumor infiltration of CD4+, CD8+ T cells mediated by the oncolytic effect of OVs and increased the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the tumor, thereby effectively enhancing the anti-tumor effect of intravenous administration of OVs. The findings of our study demonstrate that T-L@Ad11 offers a handy and efficient approach for targeting tumors, thereby enhancing the antitumor efficacy of intravenous administration of OVs.

BACKGROUND:Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM:To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS:In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS:The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION:Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

Background: Current clinical treatments for gastric cancer (GC), particularly advanced GC, lack infallible therapeutic targets.The 3′-untranslated region (3′-UTR) has attracted increasing attention as a drug target.Methods: In vitro and in vivo experiments were conducted to determine the function of FN1 3′-UTR and FN1 protein in invasion and metastasis.RNA pull-down assay and high-throughput sequencing were used to screen the factors regulated by FN1 3′-UTR and construct the regulatory network.Western blotting and polymerase chain reaction were used to examine the correlation of intermolecular expression levels.RNA-binding protein immunoprecipitation was used to verify the correlation between FN1 3′-UTR and target mRNAs. Results:The FN1 3′-UTR may have stronger prognostic implications than the FN1 protein in GC patients.Upregulation of FN1 3′-UTR significantly promoted the invasive and metastatic abilities of GC cells to a greater extent than FN1 protein in vitro and in vivo.A novel regulatory network was constructed based on the FN1 3′-UTR-let-7i-5p-THBS1 axis, wherein FN1 3′-UTR displayed stronger oncogenic effects than the FN1 protein.Conclusions: FN1 3′-UTR may be a better therapeutic target for constructing targeted drugs in GC than the FN1 protein.

Objective: To determine the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) following radical gastrectomy and to identify independent risk factors of CR-POPF. Background: CR-POPF and its sequelae are potential complications following radical gastrectomy. The reported incidence of CR-POPF was quite different across various regions, and no consensus was reached. Methods: Between December 2017 to November 2018, patients who underwent radical gastrectomy from 22 centers across 13 regions in China were prospectively recruited. The primary endpoint was the occurrence of CR-POPF, defined by the International Study Group of Pancreatic Fistula (ISGPF) in 2016. Clinically relevant change and short-term outcomes were recorded to diagnose and grade the POPF. Multivariate regression analyses were performed to identify independent risk factors of clinically relevant postoperative pancreatic fistula (CR-POPF). Results: A total of 2089 cases were analyzed. The incidence of biochemical leakage (BL) and CR-POPF were 19.6% and 1.1% respectively. All CR-POPF patients recovered well after appropriate treatment and no Grade C POPF were recorded. Logistic regression analysis showed pTNM III (OR, 2.940; 95% CI 1.180-7.325; P = 0.021) and LigaSure usage (OR, 6.618; 95% CI 1.847-23.707; P = 0.004) were independent risk factors of CR-POPF. LigaSure usage (OR, 4.817; 95% CI 1.184-19.598; P = 0.028), the drain amylase content (D-AMY) on postoperative day 3 (POD3) =5 times the upper limit of normal amylase (OR, 3.476; 95% CI 1.240-9.744; P = 0.018) and open surgery (OR, 2.463; 95% CI 1.003-6.050; P = 0.049) were independent predictors for identifying CR-POPF from BL. Conclusion: In rich-experienced gastric cancer centers, there is high prevalence of BL secondary to radical gastrectomy without clinical impact. Fewer patients suffered Grade B POPF, and Grade C POPF was less common. The patients with pTNM III or LigaSure usage were prone to suffer CR-POPF. Surgery procedure, LigaSure usage combined with D-AMY measurement on POD3 are promising for early identification of CR-POPF.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and an adaptor protein that primarily regulates adhesion signaling and cell migration. FAK promotes cell survival in response to stress. Increasing evidence has shown that at the pathological level, FAK is highly expressed in multiple tumors in several systems (including lung, liver, gastric, and colorectal cancers) and correlates with tumor aggressiveness and patient prognosis. At the molecular level, FAK promotes tumor progression mainly by altering survival signals, invasive capacity, epithelial-mesenchymal transition, the tumor microenvironment, the Warburg effect, and stemness of tumor cells. Many effective drugs have been developed based on the comprehensive role of FAK in tumor cells. In addition, its potential as a tumor marker cannot be ignored. Here, we discuss the pathological and pre-clinical evidence of the role of FAK in cancer development; we hope that these findings will assist in FAK-based clinical studies.

食管胃结合部癌(EGJ)发病率逐年升高,且Siewert Ⅱ型食管胃结合部腺癌(AEG)的治疗仍然存在较大争议.其核心问题主要围绕食管切缘和胃切除范围、淋巴结清扫范围及消化道重建方式等方面.随着国内外针对Siewert Ⅱ型AEG不断进行多学科讨论学习与验证,Siewert Ⅱ型AEG的诊疗思路日益完善和规范.我国亦通过多中心试验(CLASS-10等)不断探究Siewert Ⅱ型AEG治疗的规范化道路.相信随着越来越多的大型前瞻性临床研究的积极推进,为各学科之间的沟通合作与新技术的创新带来更多融合的可能,能够给予患者更多的生存获益.

Surgical quality is critical in cancer treatment,as it not only determines the radical resection of the primary tumor but also allows expedited postoperative recovery and early continuation of adjuvant therapy.Postoperative complications are valuable met-rics for assessing surgical quality.In gastric and colorectal cancer surgeries,postoperative complications substantially postpone patients'recovery and,in extreme cases,pose life-threatening risks[1].To reduce postoperative mortality and complications,interna-tional medical infrastructure has seen a rise in the number of national surgical databases,such as the American College of Surgeons-National Surgical Quality Improvement Program(ACS-NSQIP),Dutch Institute of Clinical Auditing(DICA),and the Japa-nese National Clinical Database(NCD)programs[2-5].

外科手术是食管胃结合部腺癌（adenocarcinoma of the esophagogastric junction，AEG）的主要治疗手段，但因其解剖所在位置和生物学行为的特殊性，其相关手术问题是肿瘤外科医生关注的热点话题，其中包括食管切缘距离。

BACKGROUND:Interferon-induced transmembrane proteins (IFITMs) are a family of proteins which functions mainly include controlling cell proliferation, promoting homotypic cell adhesion, and preventing viral infection. This research study attempts to elucidate the association between IFITM10 expression level and gastric cancer (GC).METHODS:Transcriptome sequencing and clinical information on GC and normal tissues was obtained from the Cancer Genome Atlas (TCGA) database. R and related statistical packages were used to analyze the relationship between IFITM10 and survival in GC patients based on available clinical information. Receiver operating characteristic curves (ROC) were constructed using the SPSS software package. IFITM10 expression levels in patients tissue samples were examined by qPCR and association between IFITM10 expression and clinic characteristics was analyzed using SPSS. The signaling pathway associated with IFITM10 was analyzed using gene set enrichment analysis (GSEA).RESULTS:In the TCGA database, IFITM10 was highly expressed in GC tissues (P<0.001). Area under the curve (AUC) value for IFITM10 in all samples was 0.813, while AUC value in the paired GC and adjacent tissues was 0.955. In the sample of surgical patients, IFITM10 was highly expressed in GC tissues (P<0.001). IFITM10 expression was higher in T1 and T2 tissues (P=0.042), male patients (P=0.031), and tissues without neuro infiltration (P=0.008).CONCLUSIONS:IFITM10 is highly expressed in GC and can serve as an early diagnostic indicator. High expression of IFITM10 was related to a low T stage in GC.

Gastric cancer is one of the most frequently diagnosed malignant tumors, with rapid progression and poor prognosis. The role of chondroitin sulfate synthase 1 (CHSY1) in the development and progression of gastric cancer was explored and clarified in this study. The immunohistochemistry analysis of clinical tissue samples as well as data mining of public database showed that CHSY1 was significantly upregulated in gastric cancer and associated with more advanced tumor stage and poorer prognosis. In vitro loss-of-function experiments demonstrated the inhibited cell proliferation, colony formation, cell migration, as well as the promoted cell apoptosis by CHSY1 knockdown. Moreover, recovery of CHSY1 expression could attenuate the regulatory effects induced by CHSY1 knockdown. Correspondingly, gastric cancer cells with CHSY1 knockdown showed reduced tumorigenicity and slower tumor growth in vivo. In conclusion, this study identified CHSY1 as a tumor promotor in gastric cancer, which may be utilized as a novel indicator of patients' prognosis and therapeutic target for developing more effective drug for GC treatment.

The detection rate of submucosal tumors in the gastric cardia increases year by year. Most of these tumors are benign or borderline tumors, among which leiomyoma and gastrointestinal stromal tumor are more common. The functional preservation of the gastric cardiac region is closely related to the anatomical structure of the esophagogastric junction. The esophageal reflux is mainly evaluated directly or indirectly by upper gastrointestinal radiography, gastroscopy, CT examination and manometric measurements of the lower esophagus. For tumors at this specific region, the risk of lymph node metastasis is very low, and according to the tumor free principle, usually only complete removal of the tumor is required. We aim to introduce the minimally invasive and function preserving procedures, including endoscopic therapy alone, laparoscopic and endoscopic cooperative surgery, and totally laparoscopic surgery. The selection of this tailored treatment should be based on the tumor location, size, shape and growth pattern (intraluminal or extraluminal), and the experience of the surgical team, so as to improve postoperative quality of life of the patients.