Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin’s influence on EC. This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects. Key focus areas include its impact on insulin signaling, AMP-activated protein kinase (AMPK) activation, and the mTOR pathway, which collectively contribute to its role in mitigating esophageal cancer progression. This review critically examines the body of clinical and preclinical evidence surrounding the potential role of metformin, a widely prescribed anti-diabetic medication, in EC management. Our examination extends to the modulation of inflammation, oxidative stress and angiogenesis, revealing metformin’s potential as a metabolic intervention in esophageal cancer pathogenesis. By consolidating epidemiological and clinical data, we assess the evidence that supports metformin’s candidacy as an adjuvant therapy for esophageal cancer. By summarizing clinical and preclinical findings, our review aims to enhance our understanding of metformin’s role in EC management, potentially improving patient care and outcomes.

Connexins, a family of tetraspan membrane proteins forming intercellular channels localized in gap junctions, play a pivotal role at the different stages of tumor progression presenting both pro- and anti-tumorigenic effects. Considering the potential role of connexins as tumor suppressors through multiple channel-independent mechanisms, their loss of expression may be associated with tumorigenic activity, while it is hypothesized that connexins favor the clonal expansion of tumor cells and promote cell migration, invasion, and proliferation, affecting metastasis and chemoresistance in some cases. Hepatocellular carcinoma (HCC), characterized by unfavorable prognosis and limited responsiveness to current therapeutic strategies, has been linked to gap junction proteins as tumorigenic factors with prognostic value. Notably, several members of connexins have emerged as promising markers for assessing the progression and aggressiveness of HCC, as well as the chemosensitivity and radiosensitivity of hepatocellular tumor cells. Our review sheds light on the multifaceted role of connexins in HCC pathogenesis, offering valuable insights on recent advances in determining their prognostic and therapeutic potential.

Inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) remains a significant clinical challenge due to its link with chronic inflammation and the inherent limitations of current prevention and surveillance strategies. The cGAS-STING pathway has emerged as a key player in the immune regulation of inflammation-driven carcinogenesis, demonstrating both protective and pathogenic roles. This review examines the contrasting roles of the cGAS-STING signaling pathway in intestinal inflammation and colitis-associated cancer (CAC), emphasizing its promise as a target for cancer prevention strategies. Evidence suggests that modulating this pathway could preserve epithelial integrity, limit chronic inflammation, and bolster anti-tumor immunity. Despite advancements in therapies like mesalazine and surveillance colonoscopy programs, gaps in efficacy remain, particularly for Crohn’s disease and high-risk populations. Future research should focus on integrating cGAS-STING-targeted approaches with existing modalities to provide personalized and less invasive strategies for CAC prevention. By harnessing this pathway’s therapeutic potential, a paradigm shift in managing IBD-associated CRC may be achieved, addressing the challenges of long-term disease surveillance and prevention.

Background/Objectives: Computed tomography (CT)-based radiomic analysis is an emerging technique that enables non-invasive assessment of tumor characteristics. In gastrointestinal stromal tumors (GISTs), radiomics may reflect biological behavior such as proliferative activity, often indicated by Ki-67 expression. To our knowledge, this is the first systematic review and meta-analysis synthesizing evidence on the ability of CT radiomics to predict the Ki-67 index in GISTs, addressing an important gap in the literature. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the predictive performance of CT radiomics for Ki-67 expression in GISTs. A literature search of PubMed, Scopus, Science Direct, and the Cochrane Library was performed up to December 2024 using predefined terms. Extracted data included study design, patient demographics, imaging protocols, radiomic features, and diagnostic performance. Study quality was assessed using the QUADAS-2 tool. A random-effects meta-analysis summarized the pooled area under the ROC curve (AUC), sensitivity, and specificity. Subgroup and sensitivity analyses explored heterogeneity sources. Publication bias was assessed using Egger’s test and funnel plots. Results: Six studies involving 1632 patients were included. The pooled sensitivity and specificity for predicting Ki-67 expression were 0.71 and 0.76, respectively, with a summary AUC of 0.79. Subgroup analyses showed consistent results across different imaging protocols and radiomic feature sets, though the Ki-67 cutoff (8% vs. 10%) affected diagnostic performance. Moderate heterogeneity and potential publication bias in specificity were observed. Conclusions: CT-based radiomics demonstrates moderate accuracy for non-invasively predicting Ki-67 index in GISTs. While not a substitute for histology, it may support personalized preoperative planning and guide future immunotherapy strategies. In the future, radiomic signatures—particularly when integrated with molecular or immune-related biomarkers—could help refine patient selection and monitoring strategies for emerging therapies, including immunotherapy.

Anastomotic leakage (AL) remains a major complication after esophagectomy, especially in patients with esophagogastric cancers who have undergone neoadjuvant therapies, which can impair tissue healing. Endoscopic vacuum-assisted closure (EndoVAC) is an innovative approach aimed at managing AL by facilitating wound drainage, reducing infection, and promoting granulation tissue formation, thus supporting effective healing. This review explores the role and effectiveness of EndoVAC in treating AL post-esophagectomy in esophageal cancer patients. We present an overview of its physiological principles, including wound contraction, enhanced tissue perfusion, and optimized microenvironment, which collectively accelerate wound closure. In addition, we examine clinical outcomes from recent studies, which indicate that EndoVAC is associated with improved leak resolution rates and potentially shorter hospital stays compared to traditional methods. Overall, this review highlights EndoVAC as a promising tool for AL management and underscores the need for continued investigation to refine its protocols and broaden its accessibility. By optimizing EndoVACs use, multidisciplinary teams can improve patient outcomes and advance esophageal cancer care.

Backgrounds: Gastric malignancies are exceptionally rare among children and young adults, and their clinicopathological characteristics and outcomes remain poorly defined. This study aimed to evaluate the demographic, clinical, and survival features of gastric cancer in patients aged ≤24 years using population-based data. Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016) for individuals ≤ 24 years with primary gastric malignancies. Cox proportional hazards models were used to identify predictors of overall survival (OS). Results: A total of 324 patients were included (mean age: 20 years; 50% female). Adenocarcinoma was the most common histologic subtype (52%), nearly half of which were signet ring cell carcinomas (46%). The majority of patients (59%) were diagnosed at stage IV. Median OS was 18 months, and 5-year OS was 49%. Children and adolescents (≤18 years) had significantly better survival than young adults (median OS: 34 vs. 15 months, p < 0.01). In multivariable analysis, advanced AJCC stage and higher lymph node ratio were independently associated with worse overall survival, while lymphoma histology and radiotherapy were linked to more favourable outcomes. Conclusions: Gastric cancers in patients ≤ 24 years often present at advanced stages and are dominated by aggressive histology. Prognosis is primarily determined by tumour stage, histological subtype, and lymph nodal burden. These population-based risk estimates support risk stratification and prognostic assessment in young patients by highlighting histology- and nodal-burden-driven prognostic strata.