Gastric cancer (GC) is the fifth-most common cancer worldwide and an important cause of cancer-related-death. The growing knowledge of its molecular pathogenesis has shown that GC is not a single entity, but a constellation of different diseases, each with its own molecular and clinical characteristics. Currently, surgery represents the only curative approach for localized GC, but only 20% of patients (pts) showed resectable disease at diagnosis and, even in case of curative resection, the prognosis remains poor due to the high rate of disease relapse. In this context, multimodal perioperative approaches were developed in western and eastern countries in order to decrease relapse rates and improve survival. However, there is little consensus about the optimal treatment for non-metastatic GC. In this review, we summarize the current status and future developments of perioperative chemotherapy in resectable GC, attempting to find clear answers to the real problems in clinical practice.

One of the most potent costimulatory molecules involved in the recognition and killing of tumor cells is CD80. However, its role and the molecular mechanisms regulating its expression in sporadic colorectal carcinogenesis remain elusive. Here, we provide evidence for CD80 overexpression in human colon epithelial cells derived from preneoplastic mucosa. Expression of CD80 on colonic epithelial cells isolated from normal human colonic mucosa, preneoplastic and neoplastic specimens was assessed by flow cytometry. WT and CD80KO mice received azoxymethane to induce colon preneoplastic lesions and sacrificed to perform histology, flow cytometry analysis and immunohistochemistry of colonic mucosa. Some WT mice were treated with a monoclonal anti-CD80 antibody following AOM administration. Primary colon epithelial cells and CT26 cell line were used to quantify the expression of CD80 in response to pro-oxidant stimuli. Specific pharmacological inhibitors and siRNA silencing were used to inhibit MAPK pathways and STAT3. CD80 expression was significantly increased in colon epithelial cells of human preneoplastic lesions. In the AOM model, CD80 impairment by administration of neutralizing antibodies or use of CD80 knockout mice enhanced dysplasia development. In vitro, CD80 upregulation was induced by oxidative stress in colon cancer cells and primary colon epithelial cells. In addition, reactive oxygen species could induce CD80 expression via the JNK and p38 MAPK pathways, that activated STAT3 transcription factor in colon cancer epithelial cells. This study provide evidence for a major role of CD80 in orchestrating immune surveillance of colon preneoplastic lesions and might help to develop novel approaches that exploit anti-tumor immunity to prevent and control colon cancer.

Esophageal cancer (EC) is an aggressive disease that is associated with a poor prognosis. Since metastastic EC is usually considered suitable only for palliative therapy with an estimated 5-year overall survival (OS) less than 5%, the optimal management of patients with liver oligometastatic EC (LOEC) is still undefined. The aim of this review is to provide an overview of the different treatment options for LOEC. A literature search was conducted using PubMed, Embase, and Cochrane to identify articles evaluating different treatment strategies for LOEC. Among 828 records that were identified, 20 articles met the inclusion criteria. These studies included patients who have undergone any type of surgical procedure and/or loco-regional therapy. Liver resection resulted in the best survival for patients with low tumor burden (3 lesions): 5-year OS 30–50% versus 8–12% after only chemotherapy (CHT). The 5-year OS of loco-regional therapies was 23% with a local recurrence risk ranging 0–8% for small lesions (2 to 3 cm). An aggressive multidisciplinary approach for LOEC patients may improve survival. Surgery seems to be the treatment of choice for resectable LOEC. If unfeasible, loco-regional therapies may be considered. In order to better select these patients and offer a chance of cure, prospective trials and a definition of treatment protocols are needed.

Esophageal cancer is a highly lethal malignancy, representing 5% of all cancer-related deaths. The two main subtypes are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While most research has focused on ESCC, few studies have analyzed EAC for transcriptional signatures linked to diagnosis or prognosis. In this study, we utilized single-cell RNA sequencing and bulk RNA sequencing to identify specific immune cell types that contribute to anti-tumor responses, as well as differentially expressed genes (DEGs). We have characterized transcriptional signatures, validated against a wide cohort of TCGA patients, that are capable of predicting clinical outcomes and the prognosis of EAC post-surgery with efficacy comparable to the currently accepted prognostic factors. In conclusion, our findings provide insights into the immune landscape and therapeutic targets of EAC, proposing novel immunological biomarkers for predicting prognosis, aiding in patient stratification for post-surgical outcomes, follow-up, and personalized adjuvant therapy decisions.

Esophageal cancer is an extremely deadly tumor that accounts for 5% of all cancer deaths. The two main subtypes of the disease are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To date, few studies analyse EAC for transcriptional signatures associated with diagnosis and/or prognosis, while most focus on the analysis of transcriptional profiles of ESCC. In this study, we used single-cell RNA sequencing (scRNA-seq) analysis of CD45+ cells enriched from Tumors and matched Non Tumor tissues from therapy naїve patients to identify all types of immune cells present in tumor immune infiltrate and its transcriptional profile. In addi-tion, we analysed the entire transcriptome in a cohort of 23 patients whose tissue biopsies were taken from Tumors and matched with Non Tumor tissue. The transcriptional signatures we obtained were then used to stratify a large cohort of TCGA EAC patients, demonstrating a strong association with their prognosis, as well as the ability to predict a patient's clinical outcome and better define the prognosis of EAC after surgery. In addition, these features may lead patients to effective therapies including immunotherapy approaches.

Objective: To establish a lymph node yield (LNY) change-point associated with improvements in overall survival (OS) and disease-free survival (DFS) in patients undergoing esophagectomy following neoadjuvant treatment for esophageal adenocarcinoma. Secondary endpoints include recurrence patterns and survival based on pathological staging. Summary Background Data: LNY has been associated with improved outcomes in esophageal cancer. The extent of lymphadenectomy following neoadjuvant treatment remains unclear. Methods: This multicenter European study included patients undergoing chemotherapy (CT) or chemoradiotherapy (CRT) followed by esophagectomy between 2018 and 2023. RA-CUSUM analysis identified change points between LNY and survival. Bootstrap resampling determined the optimal LNY, and multivariable Cox proportional hazards models analyzed LNY as continuous and categorical variables. A post hoc exploratory subgroup analysis was conducted in CT patients with optimal LNY compared with CRT irrespective of LNY. Recurrence patterns were assessed using the Fisher exact test. Results: A total of 2069 patients were included: 957 CT versus 1112 CRT. Median LNY was 32. CT data set: an optimal threshold of 25 nodes was identified (95% CI: 20–39). Categorical analysis using ≥25 nodes demonstrated 29% mortality reduction (HR: 0.714, P =0.0017). CRT data set: no significant LNY association across any endpoint. Continuous LNY showed a null effect ( P =0.633), and categorical analysis showed no benefit ( P =0.66). CT with ≥25 LNY had ∼44% lower mortality compared with CRT after adjustment for potential confounding variables (HR=0.563, P <0.001). Each positive LN increased the hazard for death by 7.3% in CT and 11.2% in CRT. Disease recurrence occurred in 32.7% of CT versus 38.3% of CRT ( P =0.001). Conclusion: On the basis of this data, there is a clear survival and recurrence benefit to performing a radical lymphadenectomy with a lymph node harvest of at least 25 nodes in patients who have received CT.