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Simple Summary: Minimally invasive approaches to total gastrectomy (TG) are gaining acceptance worldwide for the treatment of gastric cancer. Previous studies comparing short-term results were limited by pairwise comparisons and the inclusion of both total and distal gastrectomy. The present analysis aimed to compare the short-term outcomes of different techniques for TG comprehensively in the setting of GC. Lap-assisted TG (LATG), totally laparoscopic TG (TLTG), and robotic TG (RTG) seem to be associated with a lower overall complications rate and improved short-term functional outcomes compared to open TG (OTG). Severe postoperative complications and anastomotic leak seem comparable across techniques. Our findings support the adoption of minimally invasive TG techniques in the surgical management of gastric cancer. Background/Objectives: Total gastrectomy (TG) is the cornerstone treatment for gastric cancer (GC). While open TG (OTG) with D2 lymphadenectomy remains the gold standard, alternative techniques such as lap-assisted TG (LATG), totally laparoscopic TG (TLTG), and robotic TG (RTG) have been reported with promising outcomes. The present analysis aimed to compare the short-term outcomes of different techniques for TG comprehensively in the setting of GC. Methods: A systematic review and network meta-analysis were performed. The primary outcomes were overall complications (OC), severe postoperative complications (SPCs), and anastomotic leak (AL). Pooled effect-size measures included risk ratio (RR), weighted mean difference (WMD), and 95% credible intervals (CrIs). Results: Sixty-eight studies (44,689 patients) were included. Overall, 52.4% underwent OTG, 6.5% LATG, 39.2% TLTG, and 1.9% RTG. Both TLTG (RR 0.82; 95% CrI 0.73–0.92) and RTG (RR 0.75; 95% CrI 0.59–0.95) showed a reduced rate of postoperative OC compared to OTG. SPCs and AL RR were comparable across all techniques. Despite the longer operative time, LATG, TLTG, and RTG showed reduced intraoperative blood loss, time to first flatus, ambulation, liquid diet resumption, and hospital stay compared to OTG. Conclusions: Minimally invasive approaches seem to be associated with improved OC and functional outcomes compared to OTG. [ABSTRACT FROM AUTHOR]

Simple Summary: Para-aortic lymphadenectomy can be used for both staging and therapeutic purposes in ovarian, endometrial, gastric and bladder cancers. However, Para-aortic lymphadenectomy is associated with high rates of morbidity and mortality and with no evidence of benefits in terms of overall survival and disease-free survival. A systematic review of the literature was performed to look into the published randomized controlled studies (RCTs) that have reported the effectiveness of lymphadenectomy. The total number of patients was 4231. The studies reported that para-aortic lymphadenectomy did not improve overall survival and disease-free survival in advanced ovarian cancers, early endometrial cancers, advanced gastric, and bladder cancers. All of the studies had a low risk of bias. Conclusions: Para-aortic lymphadenectomy is not advised in advanced ovarian cancers, early endometrial cancers with low risks, advanced gastric cancers, and bladder cancers. Clinicians should inform patients regarding the benefits of para-aortic lymphadenectomy in terms of survival and the potential risks associated with it. Background: Para-aortic lymphadenectomy can be used for both diagnostic and therapeutic purposes as it aids in staging, provides prognostic data, and influences the patient's options for adjuvant therapy. However, there is still contention over its potential in treating cancer. A systematic review of the literature was performed to look into the published randomized controlled studies (RCTs) that have reported the effectiveness of lymphadenectomy. Methods: Five different electronic databases, including PubMed, Cochrane Library, Clinical trials.gov, ICTRP, and Embase, were used to conduct a comprehensive search. Original RCTs reporting on the impact of lymphadenectomy on the overall survival in various cancers were included. Information related to the study population, intervention, type of cancer, primary endpoints, and key findings of the study were extracted. Quality assessment of the selected studies was conducted using the Revised Cochrane Risk of Bias Tool Rob 2 for randomized trials. Results: A total of 1693 citations, with 1511 from PubMed, 80 from the Cochrane Library, 67 from Embase, 18 from ICTRP, and 17 from Clinicaltrials.gov were retrieved. Preliminary screening was performed, and after applying selection criteria, nine articles were included in the final qualitative analysis. The total number of patients was 4231, and the sample size ranged from 70 to 1408. Among these nine studies, four studies were on genital cancers (two ovarian cancers, one endometrial cancer, and one cervical cancer); four on digestive cancers (advanced gastric cancers); and one on urinary cancer (advanced bladder cancer). These studies reported that para-aortic lymphadenectomy did not improve overall survival and disease-free survival in advanced ovarian cancers, early endometrial cancers, advanced gastric, and bladder cancers. All of the studies had a low risk of bias. Conclusions: Para-aortic lymphadenectomy is not advised in advanced ovarian cancers, early endometrial cancers with low risks, advanced gastric cancers, and bladder cancers. SNB could be an alternative to lymphadenectomy for ovarian cancer in the future. Clinicians should inform patients regarding the benefits of para-aortic lymphadenectomy in terms of survival and the potential risks associated with it. [ABSTRACT FROM AUTHOR]

Simple Summary: A review of the latest research at PubMed and major cancer conferences was conducted to find out the current treatments for advanced stomach and esophagogastric junction cancers. In the West, neoadjuvant and perioperative chemotherapy is preferred for localized tumors. In East Asia, adjuvant chemotherapy is preferred. Studies are looking at how well immunotherapy and other drugs work in the perioperative setting. To choose the best treatment for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is important to know biomarkers like HER2 expression, PD-L1 combined positive score (CPS), Claudin 18.2, and microsatellite instability (MSI). The standard first-line therapy is a combination of fluoropyrimidine and a platinum derivative. The choice of chemotherapy with antibodies depends on the biomarker. This article reviews recent clinical trial results and looks at the future of systemic therapy. Background: The prognosis of patients diagnosed with locally advanced and metastatic gastric and esophago-gastric junction cancer is critical. The optimal choice of systemic therapy is essential to optimize survival outcomes. Methods: A comprehensive literature review via PubMed and analysis of major oncology congresses (European Society for Medical Oncology and American Society of Clinical Oncology websites) were conducted to ascertain the current status and latest developments in the systemic treatment of patients with localized or advanced gastric and esophago-gastric junction adenocarcinoma. Results: While neoadjuvant and perioperative chemotherapy for localized tumor stages is the preferred approach in the Western Hemisphere, adjuvant chemotherapy remains the preferred course of action in East Asia. The administration of chemotherapy, typically in the form of combinations comprising platinum and fluoropyrimidine compounds in combination with docetaxel, represents a standard of care. Investigations are underway into the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most appropriate therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine biomarkers such as HER2 expression, PD-L1 combined positive score (CPS) (combined positive score), Claudin 18.2, and microsatellite instability (MSI). In the present clinical context, the standard first-line therapy is a combination of fluoropyrimidine and a platinum derivative. The selection of chemotherapy in combination with antibodies is contingent upon the specific biomarker under consideration. Conclusions: This article reviews the current state of the art based on recent clinical trial results and provides an outlook on the future of systemic therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) represents a major global health challenge, ranking as the second leading cause of cancer-related deaths. The high mortality rate is primarily due to late-stage diagnoses, which limit effective treatment options. Recent research emphasizes the development of targeted therapies and radiation immunotherapy as promising alternatives to traditional approaches. The review authors summarize recent advancements in targeted therapies for gastric cancer, focusing on both laboratory and clinical studies. They explore targeted approaches that have shown potential for improving diagnostic accuracy and treatment effectiveness. The findings of this paper may significantly impact the research community by highlighting the importance of personalized medicine in gastric cancer treatment. By identifying specific molecular targets and utilizing nanotechnology for drug delivery, these advancements aim to enhance treatment efficacy while minimizing systemic toxicity. Overall, the review suggests the potential for improved prognosis and treatment strategies through targeted therapies and precision medicine. Gastric cancer (GC) is the second most common cause of cancer-related death worldwide and a serious public health concern. This high death rate is mostly caused by late-stage diagnoses, which lead to poor treatment outcomes. Radiation immunotherapy and targeted therapies are becoming increasingly popular in GC treatment, in addition to surgery and systemic chemotherapy. In this review, we have focused on both in vitro and in vivo research, which presents a summary of recent developments in targeted therapies for gastric cancer. We explore targeted therapy approaches, including integrin receptors, HER2, Claudin 18, and glutathione-responsive systems. For instance, therapies targeting the integrin receptors such as the αvβ3 and αvβ5 integrins have shown promise in enhancing diagnostic precision and treatment efficacy. Furthermore, nanotechnology provides novel approaches to targeted drug delivery and imaging. These include glutathione-responsive nanoplatforms and cyclic RGD peptide-conjugated nanoparticles. These novel strategies seek to reduce systemic toxicity while increasing specificity and efficacy. To sum up, the review addresses the significance of personalized medicine and advancements in gastric cancer-targeted therapies. It explores potential methods for enhancing gastric cancer prognosis and treatment in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates racial disparities in the stage of gastric cancer at diagnosis and overall survival among different racial groups using data from the SEER database (2018–2021). The retrospective cohort study of 18,984 patients found that Hispanics are 19% more likely to be diagnosed at a later stage of gastric cancer compared to non-Hispanics. Additionally, both Hispanics and Black patients showed poorer overall survival compared to Non-Hispanic Whites. The disparities are attributed to factors such as healthcare access, insurance coverage, language barriers, and preventive health service utilization. These findings highlight the need for targeted interventions to address these disparities in cancer outcomes. Introduction: Racial disparities in gastric cancer outcomes, including stage at diagnosis and overall survival, continue to affect Hispanic and non-Hispanic populations. This study aims to evaluate these disparities across different racial groups. Patients and methods: We conducted a retrospective cohort study using SEER data from 2018 to 2021, including 18,984 patients diagnosed with gastric cancer. Patients were selected based on ICD-O-3 codes for "stomach" with malignant behavior. Using ordered logistic regression, the association between race and stage at diagnosis was analyzed, while Cox proportional hazards models were used to assess OS and CSS. Results: Hispanic patients were significantly more likely to be diagnosed at a later stage compared to non-Hispanic patients (OR: 1.19; 95% CI: 1.10–1.28). Both Hispanic and Black patients had worse OS compared to Non-Hispanic Whites (HR 1.10 CI 1.03–1.17, p = 0.003 and HR 1.13 CI 1.04–1.22, p = 0.002, respectively) as well as CSS. Conclusions: Hispanic patients are more likely to be diagnosed with advanced-stage gastric cancer and have poorer survival outcomes compared to non-Hispanic Whites. These disparities may be linked to differences in healthcare access, insurance, language barriers, and preventive care utilization. [ABSTRACT FROM AUTHOR]

Simple Summary: We conducted a retrospective multicenter national study examining the risk of gastric and esophageal cancer in patients with type 2 diabetes who were receiving glucagon-like peptide receptor agonists. We used propensity score matching analysis to account for confounders. We assessed the risk of the outcomes in a seven-year timeframe. We add to the most recent literature findings that debunk the risk of cancers with their use. Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. Methods: We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m2, and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients' baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. Results: A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. Conclusion: The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Helicobacter pylori (Hp) eradication is known to prevent gastric cancer development. However, the efficacy of Hp eradication in preventing gastric cancer is limited, and the occurrence of gastric cancer after long-term follow-up post-eradication has been reported in many cases. In recent years, the number of gastric cancer cases detected after eradication has increased, but there is no consensus on the surveillance intervals for long-term follow-up. Although most gastric cancers detected after eradication are differentiated, undifferentiated gastric cancers are also observed. These cancer types differ in their pathological characteristics and malignancy. Therefore, these characteristics need to be considered when conducting surveillance. The purpose of this retrospective study was to characterize post-eradication differentiated and undifferentiated gastric cancers occurring more than 10 years after Hp eradication and to assist in determining appropriate surveillance intervals. Background/Objectives: Eradication therapy for Helicobacter pylori gastritis was approved for insurance coverage by the Japanese government in 2013. Since then, the incidence of gastric cancer discovered after eradication (GCAE) has increased. However, there are only a few reports of GCAE diagnosed more than 10 years after eradication. We investigated the clinicopathological characteristics of early-stage GCAE, including histological types and the interval from eradication to diagnosis. Methods: Overall, 379 patients with a total of 448 GCAE lesions treated with endoscopic resection or surgery at our hospital between January 2015 and December 2021 were assessed, and 315 patients with a known interval from eradication to diagnosis of GCAE with a total of 354 lesions were included. We classified the cases into two groups: differentiated-type GCAE (D-GCAE; 279 patients, 318 lesions) and undifferentiated-type GCAE (UD-GCAE; 36 patients, 36 lesions). Results: Smoking and a mild-to-moderate degree of atrophy were risk factors associated with differentiated-type gastric cancer occurring more than 10 years after H. pylori eradication. Additionally, the rate of a mixture of histological types with relatively high malignant potential was significantly higher in UD-GCAE presenting more than 10 years after eradication group than those presenting within 10 years after eradication. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases from gastric cancer are linked to a poor prognosis, with median survival ranging from 2 to 9 months. Standard treatments, including systemic chemotherapy and targeted therapies, have demonstrated only limited effectiveness. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an experimental approach under investigation for treating these metastases, but its widespread clinical use is hindered by insufficient evidence regarding its safety and efficacy. This retrospective study presents outcomes from the first PIPAC program in Lithuania, where 32 patients underwent 71 PIPAC procedures between 2015 and 2022. Intraoperative and postoperative complications occurred in 4.2% of cases. Although reductions in peritoneal carcinomatosis index (PCI) and ascites volume were noted, they were not statistically significant. The median overall survival after PM diagnosis was 12.5 months. These findings suggest that PIPAC is a safe and feasible treatment, but further research is needed to establish its efficacy. Background: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. Methods: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien–Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. Results: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10–17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4–10). Conclusions: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the effectiveness of salvage pembrolizumab in advanced gastric cancer (AGC) patients based on HER2 expression. Conducted at Samsung Medical Center from November 2017 to March 2023, it involved 113 patients treated with pembrolizumab. Twelve patients (10.6%) were HER2-positive, and 101 were HER2-negative. Results showed no complete responses among 92 evaluable patients. However, 50% of HER2-positive patients had a partial response compared to 4.9% of HER2-negative patients (p < 0.001). Disease control rates were 70% for HER2-positive and 37.8% for HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). This indicates that salvage pembrolizumab monotherapy is more effective in HER2-positive AGC patients. Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In overall terms, the incidence and mortality of gastric cncer have substantially decreased over the past century, attributable to decreases in risk factors such as H. pylori infection, tobacco smoking, and the intake of salt-preserved food. Nevertheless, obesity is ongoing and may result in an increase in cardia cancer, particularly in Western populations. Careful monitoring of this outcome is warranted in both Western and Asian populations. Overall, the past century has seen a substantial decline in gastric cancer, attributable to decreases in risk factors such as H. pylori infection, tobacco smoking, and the intake of salt-preserved food. One potential preventive strategy for those at high risk is H. pylori eradication for infected subjects, but confirmation of this effect awaits longer follow-up. Obesity continues to advance and may cause increases in cardia cancer, particularly in Western populations, and careful monitoring of this outcome is warranted in both Western and Asian populations. These changes in gastric cancer epidemiology foreshadow a new era in gastric cancer control and warrant further monitoring of descriptive patterns and risk factors. [ABSTRACT FROM AUTHOR]

Simple Summary: There are still limited published data on the efficacy and safety of the robotic approach in the treatment of gastric cancer in elderly patients. The present study aimed at comparing the short clinical outcomes obtained in a group of elderly patients with those obtained in a group of younger patients after robotic surgery for gastric cancer. Although the elderly patients had more frequently comorbidities than the non-elderly patients, the incidence of serious postoperative complications, re-operation rate, 30-day mortality, and median hospital stay was similar within the two groups. Even the extent and adequacy of lymphadenectomy did not differ between the two groups. Our study suggests that robotic gastrectomy can be performed safely for elderly patients and may provide new insights into the validation of the robotic approach for treatment of gastric cancer in elderly patients. Robot-assisted surgery has recently been introduced to overcome some drawbacks and technical limitations in performing laparoscopic gastrectomy. The aim of the present study was to evaluate the feasibility and safety of robotic gastrectomy in elderly patients. The study enrolled 143 patients who underwent robotic gastrectomy in a single high-volume centre. All patients were divided into two groups based on age: elderly group ≥ 75 years old (EG; n = 64) and non-elderly group < 75 years old (NEG; n = 79). Comorbidities were significantly more frequent in the EG (95.3%) than in the NEG (81%) (p = 0.011). Similarly, the percentage of ASA 3 patients was significantly higher in the EG than in the NEG (43.8% vs. 24.0%, respectively; p = 0.048). Nevertheless, the incidence of Clavien–Dindo grade III and IV complications did not differ significantly between the two groups (10.9% in the EG and 6.3% in the NEG; p = 0.852). Moreover, operative time, re-operation rate, mean number of harvested lymph nodes, 30-day mortality, and median hospital stay were similar within the two groups. Our study suggests that robotic gastrectomy can be performed safely for elderly patients. In particular, chronological age does not seem to affect either the clinical or oncological short-term outcomes after robotic gastrectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraperitoneal (IP) administration of Paclitaxel (PTX) is a logical approach for treating peritoneal metastases (PMs), as it allows direct drug infiltration into PMs, providing prolonged exposure at high concentrations with minimal systemic side effects. However, the optimal timing for combining intravenous (IV) and IP administration remains uncertain. This study demonstrated that IP administration of PTX resulted in higher concentrations of PTX in peritoneal tumors, as well as increased levels of intravenously administered Carboplatin (CBDCA) when given four days after PTX administration. These findings suggest that IP PTX may enhance the efficacy of subsequent systemic chemotherapy. Therefore, staggered and repeated systemic chemotherapy following IP PTX appears to be a highly effective strategy for managing PMs. Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs. [ABSTRACT FROM AUTHOR]

Simple Summary: Oesogastric cancers are often diagnosed at a locally advanced stage, especially in western countries. Thus, their prognosis is highly influenced by correct staging and response rate to preoperative therapy. Radiomics may offer a promising tool for improving the quality of current diagnostics of these tumors. Radiomic predictive models seem to work best when integrated with clinical characteristics. As a future perspective, the incorporation of molecular subgroup analysis to clinical and radiomic characteristics could even increase the effectiveness of these predictive and prognostic models. Background: Oesophageal, gastroesophageal, and gastric malignancies are often diagnosed at locally advanced stage and multimodal therapy is recommended to increase the chances of survival. However, given the significant variation in treatment response, there is a clear imperative to refine patient stratification. The aim of this narrative review was to explore the existing evidence and the potential of radiomics to improve staging and prediction of treatment response of oesogastric cancers. Methods: The references for this review article were identified via MEDLINE (PubMed) and Scopus searches with the terms "radiomics", "texture analysis", "oesophageal cancer", "gastroesophageal junction cancer", "oesophagogastric junction cancer", "gastric cancer", "stomach cancer", "staging", and "treatment response" until May 2024. Results: Radiomics proved to be effective in improving disease staging and prediction of treatment response for both oesophageal and gastric cancer with all imaging modalities (TC, MRI, and 18F-FDG PET/CT). The literature data on the application of radiomics to gastroesophageal junction cancer are very scarce. Radiomics models perform better when integrating different imaging modalities compared to a single radiology method and when combining clinical to radiomics features compared to only a radiomics signature. Conclusions: Radiomics shows potential in noninvasive staging and predicting response to preoperative therapy among patients with locally advanced oesogastric cancer. As a future perspective, the incorporation of molecular subgroup analysis to clinical and radiomic features may even increase the effectiveness of these predictive and prognostic models. [ABSTRACT FROM AUTHOR]

The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23-2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22-2.08, and cardia OR = 1.63, 95% CI = 0.97-2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14-2.40 and intestinal OR = 1.24, 95% CI = 0.91-1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18-1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12-1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11-1.58) and intestinal type (OR = 1.23, 95% CI = 1.07-1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and

Simple Summary: The incidence of gastric cancer (GC) is increasing. Many people receive an advanced diagnosis of GC. Furthermore, a large number of patients are surgically inoperable and are unresponsive to preoperative chemotherapy. Patients with GC do not currently have an immunotherapy option. Our study's objective was to provide insight into extracellular vesicles (EVs) and GC. EVs in GC can be studied, as this article explains. EVs screening, which is available for all patients, is an option for combatting GC. Extracellular vesicles, or EVs, are membrane-bound nanocompartments produced by tumor cells. EVs carry proteins and nucleic acids from host cells to target cells, where they can transfer lipids, proteomes, and genetic material to change the function of target cells. EVs serve as reservoirs for mobile cellular signals. The collection of EVs using less invasive processes has piqued the interest of many researchers. Exosomes carry substances that can suppress the immune system. If the results of exosome screening are negative, immunotherapy will be beneficial for GC patients. In this study, we provide an update on EVs and GC based on ongoing review papers and clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: The aging population has led to an increase in elderly patients with locally advanced gastric cancer (LAGC) requiring in-hospital care. These patients often present with higher levels of comorbidity and frailty, due to reduced physiological reserve and functional capacity, with a major susceptibility to surgery-related complications. However, the adoption of specific ERAS guidelines on gastric cancer surgery for elderly patients has been proven safe and effective, leading to optimize hospital stay and costs with equal complication rates. Prehabilitation programs also improve pre-treatment patient function, potentially enhancing their capacity to tolerate multimodal therapy. This study explores whether elderly patients affected by LAGC following an ERAS-based protocol may benefit from laparoscopic procedures, which could reduce operative stress and possibly improve survival in frail individuals. Minimally invasive surgery has provided several clinical advantages in locally advanced gastric cancer (LAGC) care, although a consensus on its application criteria remains unclear. Surgery remains a careful choice in elderly patients, who frequently present with frailty, comorbidities, and other disabling diseases. This study aims to assess the possible advantages of laparoscopic gastric resections in elderly patients presenting with LAGC. This retrospective study analyzed a single-center series of elderly patients (≥75 years) undergoing curative resections for LAGC between 2015 and 2020. A comparative analysis of open versus laparoscopic approaches was conducted, focusing on postoperative complications, length of hospital stay (LOS), and long-term survival. A total of 62 patients underwent gastrectomy through an open or a laparoscopic approach (31 pts each). The study population did not show statistically significant differences in demographics, operative risk, and neoadjuvant chemotherapy. The laparoscopic group reported significantly minimized overall complications (45.2 vs. 71%, p = 0.039) and pulmonary complications (0 vs. 9.7%, p = 0.038) as well as a shorter LOS (8 vs. 12 days, p = 0.007). Lymph node harvest was equal between the groups, although long-term overall survival presented significantly better after laparoscopic gastrectomy (p = 0.048), without a relevant difference in terms of disease-free and disease-specific survivals. Laparoscopic gastrectomy proves effective in elderly LAGC patients, offering substantial short- and long-term postoperative benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: A 90-day mortality predictive model for curative gastric cancer resection based on the Spanish EURECCA Esophagogastric Cancer database was externally validated using the GASTRODATA registry. The externally validated model showed a modestly worse performance compared to the original model, nevertheless maintaining its discriminating ability in clinical practice. Background: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. Methods: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. Results: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. Conclusion: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Using data from the Korean National Health Insurance Service—National Sample Cohort database, we evaluated whether patient-specific factors such as age, sex, income, residence, and the presence of comorbidities influence the relationship between gastric cancer (GC) and the likelihood of developing osteoporosis. Our study, with 1:4 propensity score matching and a stratified Cox proportional hazards model, showed that the hazard ratio of osteoporosis for the GC group was 1.13 (95%CI, 1.03–1.24) compared to that for the control group. In addition, subgroup analysis showed that age < 65 years, male sex, and a Charlson Comorbidity Index of 0 were risk factors for osteoporosis. Gastric cancer (GC) survivors may be more likely to develop osteoporosis. However, few studies on the relationship between GC and osteoporosis have been conducted on large patient populations. We aimed to determine the incidence of osteoporosis and identify related factors by comparing patients with GC and matched controls using the Korean National Health Insurance Service—National Sample Cohort (KNHIS-NSC). This study included 9078 patients with GC and 36,312 controls (1:4 propensity score-matched for sex, age, residence, and income). The hazard ratio (HR) for osteoporosis was significantly greater for GC patients than for controls according to Charlson Comorbidity Index (CCI) score-adjusted models (adjusted HR = 1.13). Kaplan–Meier analysis revealed that the cumulative incidence of osteoporosis during the follow-up period commencing from the index date was significantly greater in GC patients than in the controls (p = 0.0087). A positive correlation of osteoporosis with GC was detected for those aged < 65 years, males, and those with CCI scores = 0. In conclusion, the study findings suggest that men with GC aged < 65 years may be at an increased risk for osteoporosis. Research into additional risk factors and the optimal timing of interventions are needed to prevent fractures and minimize bone loss in GC survivors. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with atrophic gastritis and gastric intestinal metaplasia, considered gastric precancerous conditions (GPC), are at increased risk of developing gastric adenocarcinoma. The identification and surveillance of these patients are important for the diagnosis of early gastric neoplasia. Non-invasive markers of GPC with good diagnostic performance could allow the implementation of a stepwise screening approach and, with successful personalized endoscopic surveillance, possibly decrease gastric cancer morbidity and mortality. Pepsinogen I and II and their ratio are the most broadly investigated biomarkers with moderate diagnostic performance. Their combination with other markers like Helicobacter pylori antibodies and gastrin-17 (called GastroPanel®) allows for more precise identification of GPC but without significant improvement in overall performance. Other new serum biomarkers could possibly enhance the performance of pepsinogens. Some of them may be considered stand-alone biomarkers; however, until now, no high-quality data support the use of any of them. Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)—atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastrointestinal (GI) tumors present a significant global health challenge, prompting the need for new therapeutic strategies. Plasmacytoid dendritic cells (pDCs) are crucial in tumor immunity, with both anti-tumor and pro-tumor effects. This review examines pDC roles in various GI tumors and their potential as therapeutic targets. In gastric cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma, higher pDC infiltration correlates with worse outcomes, whereas in esophageal, pancreatic, and colorectal cancers, it improves outcomes. Overall, pDCs have a complex role in GI tumors, affecting both tumor immunity and progression. Further research is needed to refine their clinical use and explore combination therapies. Gastrointestinal (GI) tumors pose a significant global health burden, necessitating the exploration of novel therapeutic approaches. Plasmacytoid dendritic cells (pDCs) play a crucial role in tumor immunity, exhibiting both anti-tumor and pro-tumor effects. This review aims to summarize the role of pDCs in different types of GI tumors and assess their potential as therapeutic targets. In gastric cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma, increased infiltration of pDCs was associated with a worse outcome, whereas in esophageal cancer, pancreatic cancer, and colorectal cancer, pDC infiltration improved the outcome. Initial animal studies of gastric cancer and hepatocellular carcinoma showed that pDCs could be a successful therapeutic target. In conclusion, pDCs play a multifaceted role in GI tumors, influencing both anti-tumor immunity and tumor progression. Further research is needed to optimize their clinical application and explore combinatorial approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to evaluate 18 different preoperative immune, inflammatory, and nutritional scores and their best cut-off values as predictors of poorer overall survival (OS) and disease-free survival (DFS) in patients who underwent curative gastrectomy for gastric adenocarcinoma. This is a retrospective observational multicentre study based on data of the Spanish EURECCA Esophagogastric Cancer Registry. Time-dependent Youden index and log-rank test were used to obtain the best cut-offs of preoperative biomarkers for OS and DFS. The most relevant preoperative biomarkers of poorer OS and DFS were high neutrophil-to-lymphocyte ratio (NLR), high monocyte systemic inflammation index (moSII) (for stages I and III), and low prognostic nutritional index (PNI) (regardless tumour stage). Background: The aim of this study was to evaluate different preoperative immune, inflammatory, and nutritional scores and their best cut-off values as predictors of poorer overall survival (OS) and disease-free survival (DFS) in patients who underwent curative gastric cancer resection. Methods: This was a retrospective observational multicentre study based on data of the Spanish EURECCA Esophagogastric Cancer Registry. Time-dependent Youden index and log-rank test were used to obtain the best cut-offs of 18 preoperative biomarkers for OS and DFS. An adjusted Cox model with variables selected by bootstrapping was used to identify the best preoperative biomarkers, which were also analysed for every TNM stage. Results: High neutrophil-to-lymphocyte ratio (NLR), high monocyte systemic inflammation index (moSII), and low prognostic nutritional index (PNI) were identified as independent predictors of poor outcome: NLR > 5.91 (HR:1.73; 95%CI [1.23–2.43]), moSII >2027.12 (HR:2.26; 95%CI [1.36–3.78]), and PNI >40.31 (HR:0.75; 95%CI [0.58–0.96]) for 5-year OS and NLR > 6.81 (HR:1.75; 95%CI [1.24–2.45]), moSII > 2027.12 (HR:2.46; 95%CI [1.49–4.04]), and PNI > 40.31 (HR:0.77; 95%CI [0.60,0.97]) for 5-year DFS. These outcomes were maintained in the whole cohort for NLR and moSII (p < 0.05) but not in stage II and for PNI in all tumoral stages. The associations of NLR-PNI and moSII-PNI were also a relevant prognostic factor for OS. Conclusions: High NLR, high moSII (for stages I and III), and low PNI (regardless of tumour stage) were the most promising preoperative biomarkers to predict poor OS and DFS in gastric cancer patients treated with curative intent. [ABSTRACT FROM AUTHOR]

Simple Summary: ARID1A mutations are emerging as a prognostic and predictive factor in gastric cancer. Recent studies suggest their potential role in predicting patient response to novel treatment strategies including immunotherapy, poly(ADP) ribose polymerase (PARP) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors. The aim of the present review is to provide a detailed appraisal of the significance of the loss of ARID1A functionality in GCs, and examine its prognostic and therapeutic implications. AT-rich interaction domain 1 (ARID1A) is a pivotal gene with a significant role in gastrointestinal tumors which encodes a protein referred to as BAF250a or SMARCF1, an integral component of the SWI/SNF (SWItch/sucrose non-fermentable) chromatin remodeling complex. This complex is instrumental in regulating gene expression by modifying the structure of chromatin to affect the accessibility of DNA. Mutations in ARID1A have been identified in various gastrointestinal cancers, including colorectal, gastric, and pancreatic cancers. These mutations have the potential to disrupt normal SWI/SNF complex function, resulting in aberrant gene expression and potentially contributing to the initiation and progression of these malignancies. ARID1A mutations are relatively common in gastric cancer, particularly in specific adenocarcinoma subtypes. Moreover, such mutations are more frequently observed in specific molecular subtypes, such as microsatellite stable (MSS) cancers and those with a diffuse histological subtype. Understanding the presence and implications of ARID1A mutations in GC is of paramount importance for tailoring personalized treatment strategies and assessing prognosis, particularly given their potential in predicting patient response to novel treatment strategies including immunotherapy, poly(ADP) ribose polymerase (PARP) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors. [ABSTRACT FROM AUTHOR]

Simple Summary: Helicobacter pylori (H. Pylori) eradication has been the mainstream for preventing and treating gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Prior studies have shown variations in the eradication rates of H. Pylori in the US. This can influence gastric MALT lymphoma occurrence and outcomes. Therefore, we conducted a comprehensive analysis of incidence and mortality rates of gastric MALT lymphoma in different demographic-specific populations. We found that gastric MALT lymphoma incidence rates have been decreasing in the US over the past two decades. This decline was observed in both sexes, various age groups, and all race/ethnic populations except Black individuals. The decrease was also seen in early-stage tumors but not in late-stage tumors. Mortality analysis showed decreasing mortality in males, older adults, early-stage tumors, and most race/ethnic groups but not in females, younger adults, Black individuals, or late-stage tumors, which had non-decreasing rates. Our findings hold important public health implications and encourage further investigations of gastric MALT lymphoma risk factors, including disparities in H. Pylori screening, management, and outcomes. Background: Helicobacter pylori (H. Pylori) eradication has been the mainstream for preventing and treating gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Prior data showed disparities in eradication rates of H. Pylori between different populations. This can potentially impact the occurrence of gastric MALT lymphoma. There are limited data on the incidence and mortality rates and trends of gastric MALT lymphoma in the US. Therefore, the aim of the current study was to conduct a time-trend analysis of gastric MALT lymphoma incidence and mortality rates in different populations. Methods: The incidence rates of gastric MALT lymphoma were calculated from the United States Cancer Statistics (USCS) database (which covers nearly 98% of the US population) between 2001–2020 and were age-adjusted to the standard 2000 US population using SEER*Stat software (version 8.4.3, national cancer institute "NCI"). Incidence-based mortality (IBM) rates, also age-adjusted to the standard 2000 US population, were calculated from the Surveillance Epidemiology and End Results (SEER) database. Tumor location was specified using ICD-O-3 codes C 160–C 169 with malignant behavior. Histopathology was specified using the ICD-O-3 code 9699. The rates were categorized by sex, age, race/ethnicity, and tumor stage at diagnosis. Age groups were older adults (aged 55 years or older) and younger adults (aged younger than 55 years). Race/ethnic groups included Non-Hispanic White (White), Non-Hispanic Black (Black), Hispanic, Non-Hispanic Asian/Pacific Islander (API), and Non-Hispanic American Indian/Alaska Native (AI/AN), as reported in the database. Stage at diagnosis included early stage (in situ and localized tumors) and late stage (regional and distant site tumors). Joinpoint Regression Software (version 5.0.2, NCI) using the weighted Bayesian Information Criteria method was used to generate time trends. Trends were reported as annual percentage change (APC) and average APC (AAPC). Parametric estimations were used with a two-sided t-test to evaluate the trends with a p-value cutoff at 0.05. Results: There were 21,625 patients diagnosed with gastric MALT lymphoma in the US between 2001 and 2020. Overall, incidence rates were significantly decreasing over the study period (AAPC = −1.93). This decrease was seen in males (AAPC = −1.67) and in females (AAPC = −1.66) (Figure). When categorized by age groups, older adults also experienced a significant decrease in gastric MALT lymphoma incidence rates (AAPC = −1.66). While this was also seen in younger adults, the rates were decreasing at a slower pace (AAPC = −1.38). When categorizing the trends by race/ethnicity, incidence rates were significantly decreasing in White (AAPC = −2.09), Hispanic (AAPC = −1.61), and API (AAPC = −3.92) populations. However, the rates were stable among Blacks. While early-stage tumors experienced a significant decrease (AAPC = −1.10), the rates were stable for late-stage tumors. When evaluating mortality, there were 11,036 patients whose death was attributed to gastric MALT lymphoma between 2000 and 2020. IBM rates were decreasing in males (AAPC = −1.47), older adults (AAPC = −1.55), Whites (AAPC = −1.23), Hispanics (AAPC = −1.73), APIs (AAPC = −2.30), and early-stage tumors (AAPC = −1.08). On the other hand, IBM rates were stable in females, younger adults, Blacks, and late-stage tumors. Discussion: An extensive nationwide data analysis encompassing nearly 98% of patients diagnosed with gastric MALT lymphoma in the US unveils a declining trend in the incidence of cancer overall over the past two decades. This decline is observed in both sexes and various age groups. When stratifying by race and ethnicity, this incidence has been decreasing in all populations except among Black individuals. While early-stage tumors have also demonstrated a significant decrease in incidence rates, late-stage tumors have shown no parallel decline. Mortality evaluation also revealed an improvement in most of the US population except among females, younger adults, Black individuals, and late-stage tumors. While the cause of our findings is unclear, it could be driven by disproportionate exposure to risk factors, including H. Pylori, and disparities in screening, management, and outcomes. Future studies are warranted to investigate factors contributing to worse outcomes of gastric MALT lymphoma, especially in the Black population. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary risk regarding Helicobacter pylori infection is that it is associated with gastric cancer. The lack of eradication of Helicobacter pylori has led to an increase in the prevalence of gastric cancer. We examined the literature from the year 2024 related to the Helicobacter pylori/gastric cancer association. Immunological studies increased, but they did not convince in the study of this infection. Most of the examined studies address the clinical treatment of this bacterium. However, to the same extent, other studies have investigated genetically individualized treatment. If, until now, clinical treatments have not yet been able to eradicate this bacterium, we recommend genetically individualized treatment. Numerous studies have been performed on Helicobacter pylori infection because of the high death rate linked to this illness and gastric cancer. An update on the key developments in recent years in the investigation of Helicobacter pylori and gastric cancer is the goal of this review. Using the search term "Helicobacter pylori, gastric cancer", the PubMed database was searched. Only papers published in 2024 fulfilled the inclusion criteria. Because case report papers were not part of our investigation, they satisfied the exclusion criteria. Most of the research on the variable genes of Helicobacter pylori is guided by genetics to determine potential treatments. Studies on clinical treatments for the eradication of H. pylori with promising therapeutic options are needed. We found the fewest studies related to the immunopathology of H. pylori infection, which is still unknown. In conclusion, priority should be given to this kind of research. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal disease in gastric cancer has a poor prognosis, with a median survival of 3–6 months and a 5-year survival rate of 0%. Despite multiple advancements in therapeutics, the National Comprehensive Cancer Network (NCCN) guidelines recommend systemic chemotherapy or best supportive care for GC with peritoneal dissemination. According to several studies, CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC. Background: Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. Methods: A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. Results: Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8–28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9–8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (−1.8954 (95% CI: −2.5761 to −1.2146; p < 0.001). Conclusions: CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC. [ABSTRACT FROM AUTHOR]

Simple Summary: As the precursor of pepsin, Pepsinogen C (PGC) is the final product of the maturation and differentiation of gastric mucosa cells. The latest bioinformatics analysis found that PGC may play a little-known role in the carcinogenic process, but there is no relevant experimental evidence to prove the effect of PGC on the biological function of cancer cells. In our research, we found PGC may act as a tumor suppressor in the development and metastasis of gastric cancer. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of gastric cancer cell migration and invasion. Thus, PGC has the potential to be a new therapeutic target for gastric cancer. Aim: This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. Method: The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR. Results: PGC inhibited the proliferation, viability, epithelial–mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated. Conclusion: PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion. [ABSTRACT FROM AUTHOR]

Simple Summary: Human epidermal receptor (HER) 2-positive advanced gastric cancer (AGC) is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. After the success of a ToGA trial, the development of treatment for HER2-positive AGC had been at a standstill for a long time. Recently, trastuzumab deruxtecan in later-line therapy and the combination therapy of chemotherapy plus trastuzumab with immune checkpoint inhibitor has demonstrated significant survival benefit in first-line treatment. Currently, several clinical trials of new types of anti-HER2 agents are ongoing. Human epidermal receptor (HER) 2-positive advanced gastric cancer is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. Although combination therapy with trastuzumab and chemotherapy provides meaningful survival benefit, clinical trials targeting HER2 have failed to demonstrate clinical benefits in first- or subsequent-line treatment. Trastuzumab deruxtecan, an antibody–drug conjugate, has shown positive results even in later-line treatment and has become new standard treatment. In first-line therapy, combination therapy with pembrolizumab and trastuzumab plus chemotherapy demonstrated a dramatic response rate. Therefore, the FDA rapidly approved it without waiting for the results of survival time. The emergence of combination therapy including immunotherapy with HER2-targeting agents and the development of HER2 targeting agents with or without immunotherapy have been advancing for treating HER2-positive gastric cancer. In this review, we will discuss the current status of treatment development and future perspectives for HER2-positive gastric cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Significant progress has been made in the surgical treatment of stomach cancer. A shift towards less invasive techniques is evident, and new methods continue to evolve. Laparoscopic surgery is widely adopted and its indications have steadily expanded, while robot-assisted surgery is being introduced in clinical practice. Function-preserving surgery, which retains the stomach's capacity and digestive function, has now been established as a valid option for early-stage tumors. Currently, more limited procedures are being explored, such as sentinel node navigation surgery, which seeks to target only the specific lymph nodes most likely to be affected. The goal of these efforts is to reduce postoperative complications, accelerate recovery, minimize the impact on nutritional status, and preserve the quality of life of patients following surgery. This review aims to provide an up-to-date overview of the current state of surgical treatment for stomach cancer, addressing established practices, emerging trends, and future directions. Significant progress has been made in the surgical management of gastric cancer over the years, and previous discrepancies in surgical practice between different parts of the world have gradually lessened. A transition from the earlier period of progressively more extensive surgery to the current trend of a more tailored and evidence-based approach is clear. Prophylactic resection of adjacent anatomical structures or neighboring organs and extensive lymph node dissections that were once assumed to increase the chances of long-term survival are now performed selectively. Laparoscopic gastrectomy has been widely adopted and its indications have steadily expanded, from early cancers located in the distal part of the stomach, to locally advanced tumors where total gastrectomy is required. In parallel, function-preserving surgery has also evolved and now constitutes a valid option for early gastric cancer. Pylorus-preserving and proximal gastrectomy have improved the postoperative quality of life of patients, and sentinel node navigation surgery is being explored as the next step in the process of further refining the minimally invasive concept. Moreover, innovative techniques such as indocyanine green fluorescence imaging and robot-assisted gastrectomy are being introduced in clinical practice. These technologies hold promise for enhancing surgical precision, ultimately improving the oncological and functional outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome, among patients with gastric cancer. Textbook Neoadjuvant Outcome integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of gastric cancer patients undergoing neoadjuvant chemotherapy to identify the treatment- and patient-related data required to establish high-quality oncological care further. The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the "All or None" method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the "ideal" and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one), a flavonoid, is richly found in fruits and vegetables. Kaempferol has been proven to reduce tumor cell growth by modulating several pathways and molecular mechanisms, such as causing G0/G1 phase arrest in esophageal cancer, reducing G2/M cell cycle proteins in gastric cancer, inducing apoptosis by Akt/mTOR pathway in pancreatic cancer, causing cell cycle arrest (especially HT-29 human colon cancer cells), and suppressing cell growth by PI3K/mTOR/MMP signaling pathways in liver cancer. The application of nanotechnology has been shown to enhance the efficacy of kaempferol against gastrointestinal cancer. Mechanistic studies showed kaempferol-conjugated nanoparticles inducing oxidative stress-mediated apoptosis and cell cycle arrest in liver cancer cells, potentially leading to anti-cancer effects. Notably, kaempferol-conjugated gold nanoclusters have also shown efficacy in reducing tumor volume in vivo. However, there is a lack of research specifically focused on gastrointestinal cancers, highlighting the need for further exploration in this area. In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The prevalence of cancer related to the digestive system keeps rising. We examined the 2024 literature on gastric cancer. Apart from surgery, which remains the primary treatment option for gastric cancer, immunotherapy and therapeutic targeting are becoming increasingly significant in the management of this disease. Following gastric cancer surgery, a multidisciplinary approach is required, with nutritionists and psychologists playing fundamental roles. Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term "gastric cancer" to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori, and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the significant improvements in the diagnosis and therapeutic strategies for gastric cancer, this malignancy still remains one of the most prevalent worldwide, with a significant mortality rate. Recently, the number of studies concerning herbal medicine and its use in various cancers has increased significantly. For example, there has been research focusing on its applications alone or in combination with other therapeutic strategies, such as chemotherapy. Therefore, because of the continuous research on newer spices, we aimed to summarize the current knowledge regarding the application of herbal medicine in gastric cancer patients, taking into account their potential as a part of potential cancer therapy. Besides providing a summary of the potential alternative therapeutic approaches for gastric cancer, the findings of this paper might provide insight into further research directions. Gastric cancer (GC) ranks third in terms of cancer-related deaths and is the fifth most commonly diagnosed type of cancer. Its risk factors include Helicobacter pylori infection, Epstein–Barr virus infection, the consumption of broiled and charbroiled animal meats, salt-preserved and smoke-enhanced foods, alcohol drinking, tobacco smoking, exposure to ionizing radiation, and positive family history. The limited effectiveness of conventional therapies and the widespread risk factors of GC encourage the search for new methods of treatment and prevention. In the quest for cheap and commonly available medications, numerous studies focus on herbal medicine, traditional brews, and spices. In this review, we outline the potential use of spices, including turmeric, ginger, garlic, black cumin, chili pepper, saffron, black pepper, rosemary, galangal, coriander, wasabi, cinnamon, oregano, cardamom, fenugreek, caraway, clove, dill, thyme, Piper sarmentosum, basil, as well as the compounds they contain, in the prevention and treatment of GC. We present the potential molecular mechanisms responsible for the effectivity of a given seasoning substance and their impact on GC cells. We discuss their potential effects on proliferation, apoptosis, and migration. For most of the spices discussed, we also outline the unavailability and side effects of their use. [ABSTRACT FROM AUTHOR]

Simple Summary: In this investigation, we analyzed the number, type, and location of immune cells within surgically resected gastric cancer specimens treated with or without preoperative chemotherapy. We hypothesized that chemotherapy can stimulate the host immune system, as evidenced by an increased number of anti-tumor infiltrating lymphocytes in the tumor microenvironment. We found significantly elevated levels of immune cells within chemotherapy-treated tumors compared with chemotherapy-naïve specimens. We also revealed important associations between survival and immune lymphocytes in the tumor-related stromal tissue. Together, we added evidence supporting the immunostimulatory role of chemotherapy and underscore the potential utility of immunotherapy in resectable gastric cancer. Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles, as evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, as well as total TILs (CD4+, CD8+, Treg, B cells), within chemotherapy-treated tumors compared with chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic responses with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherapy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery with adequate lymphadenectomy (D2) currently represents the standard of care for resectable gastric cancer under most guidelines. However, super-extended lymphadenectomy (D2plus) may offer better locoregional control in advanced stages with a high risk of metastases to third-level nodes. In recent years, preoperative chemotherapy has become a novel issue in patients with locally advanced gastric cancer. To date, only a few studies have evaluated D2plus lymphadenectomy in patients with locally advanced or oligometastatic gastric cancer after preoperative therapy. The present study included a large series when compared with the current literature and reports limited morbidity/mortality rates and relevant survival outcomes. Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13–106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13–18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Biomarker-guided therapies offer the possibility for targeted cancer therapies. For gastric cancer, HER2 plays a pivotal role. To date, with trastuzumab and trastuzumab-deruxtecan, two HER2-targeting options exist for the treatment of metastatic HER2-positive gastric cancer. However, these therapies rarely lead to long-lasting results as resistance mechanisms and heterogeneity limit their success. This review gives an overview of the current standard-of-care treatment of HER2-positive gastric cancer and new developments in the field. Despite a decreasing incidence in Western countries, gastric cancer is among the most common cancer subtypes globally and is associated with one of the highest tumor-related mortality rates. Biomarkers play an increasing role in the treatment against gastric cancer. HER2 was one of the first biomarkers that found its way into clinical practice. Since the ToGA trial, trastuzumab has been part of first-line palliative chemotherapy in metastatic or unresectable gastric cancer. HER2-targeting agents, such as the tyrosine kinase inhibitor lapatinib, the antibody drug conjugate (ADC) trastuzumab-emtansine or dual HER2 inhibition (pertuzumab and trastuzumab), have been investigated in the second-line setting but led to negative study results. More recently, the ADC trastuzumab-deruxtecan was authorized after the failure of trastuzumab-based treatment. However, further improvements in HER2-directed therapy are required as resistance mechanisms and HER2 heterogeneity limit the existing treatment options. This review aims to give an overview of the current standard-of-care HER2-directed therapy in gastric cancer, as well as its challenges and future developments. [ABSTRACT FROM AUTHOR]

Simple Summary: In the current study, we have collected real-world population data from the Netherlands Cancer Registry of patients who underwent perioperative anthracyclin triplets or FLOT. Our study showed no significant overall survival improvement for FLOT-treated patients compared to anthracyclin triplets, despite more staging laparoscopies in the first group. However, FLOT patients demonstrated higher rates of neoadjuvant therapy completion, proceeding to adjuvant therapy, and increased pathological complete response rates. Even though survival difference failed to reach statistical significance, we believe that our findings hold significance as they mirror the outcomes observed in clinical practice, outside the controlled environment of a clinical trial. Background: The FLOT4-AIO trial (2019) showed improved survival with perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) compared to anthracyclin triplets in gastric cancer treatment. It is unclear whether these results extend to real-world scenarios in the Netherlands. This study aimed to compare outcomes of perioperative FLOT to anthracyclin triplets in a real-world Dutch gastric cancer population. Methods: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) gastric or gastro-esophageal junction carcinoma between 2015–2021 who received neoadjuvant FLOT or anthracyclin triplets were selected from the Netherlands Cancer Registry. The primary outcome was overall survival (OS), analyzed through multivariable Cox regression. Secondary outcomes included pathological complete response (pCR), neoadjuvant chemotherapy cycle completion, surgical resection rates, and adjuvant therapy. Results: Adjusted OS showed no significant survival benefit (HR = 0.88, 95% CI 0.77–1.01, p = 0.07), even though the median OS was numerically improved by 8 months with FLOT compared to anthracyclin triplets (48.1 vs. 39.9 months, p = 0.16). FLOT patients were more likely to undergo diagnostic staging laparoscopies (74.2% vs. 44.1%, p < 0.001), had higher rates of completing neoadjuvant chemotherapy (OR = 1.35, 95% CI 1.09–1.68, p = 0.007), receiving adjuvant therapy (OR = 1.34, 95% CI 1.08–1.66, p = 0.08), and achieving pCR (OR = 1.52, 95% CI 1.05–2.20, p = 0.03). No significant differences were observed in (radical) resection rates. Conclusion(s): Real-world data showed no significant OS improvement for FLOT-treated patients compared to anthracyclin triplets, despite more staging laparoscopies. However, FLOT patients demonstrated higher rates of neoadjuvant therapy completion, proceeding to adjuvant therapy, and increased pCR rates. Therefore, we recommend the continued use of neoadjuvant FLOT therapy in the current clinical setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Stomach cancer is rarely diagnosed at early stages, while it is still easy to cure. We gathered information from national registries and evaluated all patients with early stomach cancer in a defined healthcare region and re-examined tissue samples to characterize this group. We found that only 88 of 1205 stomach cancers from 2001 to 2016 were early cancers, with no major change in how common early cancers were during the 15-year study period. Specific features of the early gastric cancer (EGC), such as size, growth depth, growth into veins, and ulceration, were associated with spreading to regional lymph nodes. The patients were followed up for a minimum of five years after the operation, and most died of causes unrelated to stomach cancer. However, 12.7% of the deaths were cancer-related, with similar proportions being due to complications after surgery and recurrence of EGC, which could manifest itself more than five years after diagnosis. Early gastric cancers (EGCs) are confined to the gastric mucosa and submucosa irrespective of lymph node metastases and constitute only a minor proportion of gastric cancer in Western countries. We aimed to characterize EGCs and assess the survival of EGC in Central Norway during 2001–2016. A retrospective population-based study on 1205 patients with gastric cancer was performed. At the time, surgical resection was the standard treatment, and 88 (7.3%) EGCs were identified. Histopathological specimens were re-examined, and the eCura score and survival were evaluated. The number of gastric cancers declined (p = 0.010), but the relative proportion of EGC was unchanged during the study period. EGCs were more often of the Lauren intestinal type (p < 0.001) compared with controls. A significant proportion (9.4%, n = 5) of the patients with a low-risk eCura had lymph node metastases, whereas further exclusion of tumors with histological ulceration or SM2 invasion identified an N0 cohort. The median survival for EGC patients was 117.1 months (95% CI 99.8–134.3) and the 5-year overall survival was 75%. Twelve deaths were cancer-related, either due to postoperative complications (5.7%, n = 5) or cancer recurrence (8%, n = 7). In conclusion, EGCs constituted a minor but constant proportion of gastric cancers. eCura alone was insufficient in predicting patients with pN0 disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with advanced gastric cancer (AGC) often discontinue treatment when peritoneal metastases progress, particularly during second- or third-line chemotherapy. To prevent serious complications like bowel obstruction or increased ascites burden, it is crucial to identify predictors of peritoneal metastases before they occur. In this study, serum carbohydrate antigen 125 (CA125) concentrations were found to be associated with increased ascites burden in patients with AGC and served as a prognostic factor. Moreover, CA125 kinetics, measured at a median interval of 28 days after initiating taxane-plus-ramucirumab treatment, were found to be associated with the ascites response. Furthermore, an increase in CA125 concentration exceeding 0.0067% per day, as determined by receiver operating characteristic curve analysis, predicted the progression of peritoneal metastases. Thus, monitoring CA125 kinetics is vital for predicting the progression of peritoneal metastases and can help determine the optimal timing for subsequent chemotherapy. Currently, no established marker exists for predicting peritoneal metastasis progression during chemotherapy, although they are major interruptive factors in sequential chemotherapy in patients with advanced gastric cancer (AGC). This multicenter retrospective study was conducted from June 2015 to July 2019, analyzing 73 patients with AGC who underwent taxane-plus-ramucirumab (TAX/RAM) therapy and had their serum carbohydrate antigen 125 (CA125) concentrations measured. Of 31 patients with elevated CA125 levels above a cutoff of 35 U/mL, 25 (80.6%) had peritoneal metastasis. The CA125 concentrations before TAX/RAM treatment were associated with ascites burden. The overall survival was significantly shorter in the CA125-elevated group. CA125 kinetics, measured at a median of 28 days after chemotherapy, were associated with the ascites response (complete or partial response: −1.86%/day; stable disease: 0.28%/day; progressive disease: 2.33%/day). Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Inflammatory biomarkers have been widely investigated as potential predictors of prognosis among patients with gastric cancer (GC). Recently, a novel cancer biomarker, the inflammation burden index (IBI), was proposed, which is defined as the product of C-reactive protein multiplied by the neutrophil/lymphocyte ratio. The IBI comprehensively evaluates inflammatory load in cancer patients, and to date, IBI has been validated only in the Eastern population, which is known for genetic and clinicopathological differences from Western GC patients. Therefore, this study aimed to evaluate IBI as a prognostic biomarker among Central European patients undergoing multimodal treatment for GC. A low IBI was observed among patients obtaining neoadjuvant chemotherapy (NAC), and a high IBI was associated with an increased risk of postoperative complications and a higher mortality rate. IBI might help tailor treatment decision making. However, it requires further validation in a large prospective population-based study. Since increasing evidence underlines the prominent role of systemic inflammation in carcinogenesis, the inflammation burden index (IBI) has emerged as a promising biomarker to estimate survival outcomes among cancer patients. The IBI has only been validated in Eastern gastric cancer (GC) patients; therefore, the aim of this study was to evaluate the IBI as a prognostic biomarker in Central European GC patients undergoing multimodal treatment. Ninety-three patients with histologically confirmed GC who underwent multimodal treatment between 2013 and 2021 were included. Patient recruitment started with the standardization of neoadjuvant chemotherapy (NAC). Blood samples were obtained one day prior to surgical treatment. The textbook outcome (TO) served as the measure of surgical quality, and tumor responses to NAC were evaluated according to Becker's system tumor regression grade (TRG). A high IBI was associated with an increased risk of postoperative complications (OR 2.95, 95% CI 1.13–7.72). In multivariate analysis, a high IBI (HR = 2.56, 95% CI 1.28–5.13) and a high neutrophil-to-lymphocyte ratio (NLR, HR = 2.55, 95% CI 1.32–4.94) were associated with an increased risk of death, while NAC administration (HR = 0.40, 95% CI 0.18–0.90) and TO achievement (HR = 0.42, 95% CI 0.22–0.81) were associated with a lower risk of death. The IBI was associated with postoperative complications and mortality among GC patients undergoing multimodal treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with gastric cancer who underwent gastrectomy after surgery had a poor long-term prognosis when postoperative complications occurred. However, the relationship between preoperative inflammation and postoperative complications in patients with gastric cancer who underwent gastrectomy remains unclear. For example, it has been suggested that intervention methods may differ depending on whether chronic inflammation is present in patients with malnutrition. This study aimed to determine the relationship between preoperative mild inflammation and postoperative complications in patients with gastric cancer after gastrectomy. As a result, management to ameliorate inflammation is necessary if preoperative chronic inflammation is present. The purpose of this study was to investigate the association between preoperative inflammation and postoperative complications in gastric cancer patients having elective gastrectomy. Participants in this study were those who underwent radical gastrectomy between April 2008 and June 2018 and were diagnosed with stage I–III primary gastric cancer. Preoperative CRP values were used to divide the patients into two groups: the inflammation group comprised individuals having a CRP level of ≥0.5 mg/dL; the other was the non-inflammation group. The primary outcome was overall complications of Clavien–Dindo grade II or higher after surgery. Using propensity score matching to adjust for background, we compared the postoperative outcomes of the groups and conducted a multivariate analysis to identify risk variables for complications. Of 951 patients, 852 (89.6%) were in the non-inflammation group and 99 (10.4%) were in the inflammation group. After matching, both groups included 99 patients, and no significant differences in patient characteristics were observed between both groups. The inflammation group had a significantly greater total number of postoperative complications (p = 0.019). The multivariate analysis revealed that a preoperative CRP level of ≥0.5 mg/dL was an independent risk factor for total postoperative complications in all patients (odds ratio: 2.310, 95% confidence interval: 1.430–3.730, p < 0.001). In conclusion, in patients undergoing curative resection for gastric cancer, preoperative inflammation has been found to be an independent risk factor for overall complications after surgery. Patients with chronic inflammation require preoperative treatment to reduce inflammation because chronic inflammation is the greatest risk factor for postoperative complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 10–12% of patients present with oligometastatic disease (OMD) from oesophageal or gastric cancer (OGC). Potential curative treatment is debated in these patients, especially when located in the liver. The aim of this study was to describe the outcomes of patients who underwent surgical treatment of the primary tumour together with local treatment of synchronous liver metastases. We report a 5-year survival of 30%, but disease recurred in 80% of patients. Patients with a solitary liver metastasis may have the best prognosis, but more data are needed to optimise patient selection for curative treatment. Approximately 10–12% of patients with oesophageal or gastric cancer (OGC) present with oligometastatic disease at diagnosis. It remains unclear if there is a role for radical surgery in these patients. We aimed to assess the outcomes of OGC patients who underwent simultaneous treatment for the primary tumour and synchronous liver metastases. Patients with OGC who underwent surgical treatment between 2008 and 2020 for the primary tumour and up to five synchronous liver metastases aiming for complete tumour removal or ablation (i.e., no residual tumour) were identified from four institutional databases. The primary outcome was overall survival (OS), calculated with the Kaplan–Meier method. Secondary outcomes were disease-free survival and postoperative outcomes. Thirty-one patients were included, with complete follow-up data for 30 patients. Twenty-six patients (84%) received neoadjuvant therapy followed by response evaluation. Median OS was 21 months [IQR 9–36] with 2- and 5-year survival rates of 43% and 30%, respectively. While disease recurred in 80% of patients (20 of 25 patients) after radical resection, patients with a solitary liver metastasis had a median OS of 34 months. The number of liver metastases was a prognostic factor for OS (solitary metastasis aHR 0.330; p-value = 0.025). Thirty-day mortality was zero and complications occurred in 55% of patients. Long-term survival can be achieved in well-selected patients who undergo surgical resection of the primary tumour and local treatment of synchronous liver metastases. In particular, patients with a solitary liver metastasis seem to have a favourable prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Traditional survival models estimate risk across many patients, and thus, translating survival outcomes to individual patients is a difficult task. Individual survival distributions (ISDs) provide an accurate survival curve for each individual patient. In this study, we demonstrate that ISDs established with multi-task logistic regression (MTLR) models provide accurate individual survival predictions for gastric cancer. Because MTLR is not bound by traditional assumptions, we demonstrate that the degree to which a tumour has a favourable immune system interaction has the most relevant long-term survival effects. Recent advances in our understanding of gastric cancer biology have prompted a shift towards more personalized therapy. However, results are based on population-based survival analyses, which evaluate the average survival effects of entire treatment groups or single prognostic variables. This study uses a personalized survival modelling approach called individual survival distributions (ISDs) with the multi-task logistic regression (MTLR) model to provide novel insight into personalized survival in gastric adenocarcinoma. We performed a pooled analysis using 1043 patients from a previously characterized database annotated with molecular subtypes from the Cancer Genome Atlas, Asian Cancer Research Group, and tumour microenvironment (TME) score. The MTLR model achieved a 5-fold cross-validated concordance index of 72.1 ± 3.3%. This model found that the TME score and chemotherapy had similar survival effects over the entire study time. The TME score provided the greatest survival benefit beyond a 5-year follow-up. Stage III and Stage IV disease contributed the greatest negative effect on survival. The MTLR model weights were significantly correlated with the Cox model coefficients (Pearson coefficient = 0.86, p < 0.0001). We illustrate how ISDs can accurately predict the survival time for each patient, which is especially relevant in cases of molecular subtype heterogeneity. This study provides evidence that the TME score is principally associated with long-term survival in gastric adenocarcinoma. Additional external validation and investigation into the clinical utility of this ISD model in gastric cancer is an area of future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite remarkable progress in treating early-stage gastric cancer (GC), the clinical outcomes for patients with advanced disease remain very poor. Tissue invasion and metastasis constitute the major causes of cancer-related deaths, including GC. This highlights the urgent need to develop animal models that can recapitulate these processes to develop novel therapeutic strategies. We developed a highly reproducible and cost-effective procedure to establish orthotopic GC xenografts showing high engraftment and metastatic rates via the direct implantation of tumor cell suspensions. Compared with the routine method to establish orthotopic xenograft models by engrafting intact tumor fragments, our approach significantly shortens the experimental timeline and allows for the flexible adjustment of the number of tumor cells implanted to control the rate of tumor progression. Both dose- and time-dependent progressions of tumor invasion and metastasis were nicely recapitulated in our model. Our work provides valuable tools for studying GC progression and metastasis and developing effective therapies. Although the implantation of intact tumor fragments is a common practice to generate orthotopic xenografts to study tumor invasion and metastasis, the direct implantation of tumor cell suspensions is necessary when prior manipulations of tumor cells are required. However, the establishment of orthotopic xenografts using tumor cell suspensions is not mature, and a comparative study directly comparing their engraftment and metastatic capabilities is lacking. It is unclear whether tumor fragments are superior to cell suspensions for successful engraftment and metastasis. In this study, we employed three GC cell lines with varying metastatic capacities to stably express firefly luciferase for monitoring tumor progression in real time. We successfully minimized the risk of cell leakage during the orthotopic injection of tumor cell suspensions without Corning Matrigel by systematically optimizing the surgical procedure, injection volume, and needle size options. Comparable high engraftment and metastatic rates between these two methods were demonstrated using MKN-45 cells with a strong metastatic ability. Importantly, our approach can adjust the rate of tumor progression flexibly and cuts the experimental timeline from 10–12 weeks (for tumor fragments) to 4–5 weeks. Collectively, we provided a highly reproducible procedure with a shortened experimental timeline and low cost for establishing orthotopic GC xenografts via the direct implantation of tumor cell suspensions. [ABSTRACT FROM AUTHOR]

Simple Summary: The response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. The elevated level of IL-6 prior to treatment and cycle 2 of the FLOT regimen might be a predictor of pathological response to NAC in locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer. The results were obtained from a small group of patients and currently cannot be used in everyday clinical practice. Confirmation of the results in a larger group of patients seems to be essential from a clinical point of view, bearing in mind that IL-6 plays a significant role in gastric cancer biology, particularly in metastasis formation and in the mechanism of chemotherapeutic resistance. Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. Methods: We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Results: Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022). Conclusions: The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC. [ABSTRACT FROM AUTHOR]

Simple Summary: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. However, HP eradication is generally considered to be effective in preventing gastric cancer. Due to these contradictory facts, it remains unclear whether the impact of HP eradication on the clinical course of GC is truly beneficial. In this retrospective multicenter study conducted over 5 years, a total of 231 patients with GCs were newly diagnosed and enrolled exclusively through screening endoscopy. Propensity analysis showed that HP eradication was not significantly associated with deeper tumor invasion. HP eradication did not lead to delayed diagnosis of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases. Background: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. Methods: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. Results: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b–T4-GCs and T1b2–T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48–2.81) and 1.16 (0.42–3.19), respectively. Conclusions: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: This study was conducted to compare two endoscopic procedures for managing malignant gastric outlet obstruction. The first and most commonly used procedure is enteral stenting, which is safe, easy, and widely available. The second procedure, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), is more challenging, can result in severe adverse events, and requires specific skills. However, EUS-GE, which bypasses the tumor, could have some advantages in terms of the stent dysfunction rate. Our study found that stent dysfunction occurred more frequently after enteral stenting, while stent patency was longer after EUS-GE. However, the early clinical efficacy was comparable between the two procedures and was influenced by patients' performance status. This study suggests that the choice between these two techniques should be personalized based on several factors, including patients' prognosis and life expectancy, clinical success, and local expertise. Background: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen apposing metal stent has emerged as a minimally invasive treatment for the management of malignant gastric outlet obstruction (mGOO). We aimed to compare EUS-GE with enteral stenting (ES) for the treatment of mGOO. Methods: Patients who underwent EUS-GE or ES for mGOO between June 2017 and June 2023 at two Italian centers were retrospectively identified. The primary outcome was stent dysfunction. Secondary outcomes included technical success, clinical failure, safety, and hospital length of stay. A propensity score-matching analysis was performed using multiple covariates. Results: Overall, 198 patients were included (66 EUS-GE and 132 ES). The stent dysfunction rate was 3.1% and 16.9% following EUS-GE and ES, respectively (p = 0.004). Using propensity score-matching, 45 patients were allocated to each group. The technical success rate was 100% for both groups. Stent dysfunction was higher in the ES group compared with the EUS-GE group (20% versus 4.4%, respectively; p = 0.022) without differences in clinical efficacy (p = 0.266) and safety (p = 0.085). A significantly shorter hospital stay was associated with EUS-GE compared with ES (7.5 ± 4.9 days vs. 12.5 ± 13.0 days, respectively; p = 0.018). Kaplan–Meier analyses confirmed a higher stent dysfunction-free survival rate after EUS-GE compared with ES (log-rank test; p = 0.05). Conclusion: EUS-GE offers lower rates of stent dysfunction, longer stent patency, and shorter hospital stay compared with ES. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer is a major global health issue, ranking among the top causes of cancer-related deaths. Unfortunately, most patients are diagnosed in advanced stages, with only a 6% chance of surviving five years. Current treatment involves a specific drug combination, but predicting its effectiveness is challenging. This review explores the changing world of gastric cancer markers, focusing on Claudin 18.2 (CLDN18.2) as a promising target. Recent trials show that Zolbetuximab, a CLDN18.2-targeting drug, works well with chemotherapy for CLDN18.2-positive gastric cancer. Understanding how to choose these therapies is crucial as this new approach unfolds. This review aims to overview new strategies in managing CLDN18.2 positive advanced gastric cancer. Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC. [ABSTRACT FROM AUTHOR]

Simple Summary: Oligometastatic cancer describes an intermediate stage of cancer between localized and widely spread disease. Oligometastasis can be treated with local treatments, such as surgical removal or radiotherapy. The concept of oligometastasis is also observed in the field of gastric cancer. However, the definition of oligometastasis in gastric cancer is not yet established. Metastatic lesions that are localized and technically removable at diagnosis and that demonstrate a certain response to chemotherapy sometimes present a favorable survival outcome with local treatment. Those metastatic lesions are considered oligometastasis in the field of gastric cancer. Major guidelines for gastric cancer describe the concept of oligometastasis, and a European multicenter board of experts organized the OligoMetastatic Esophagogastric Cancer Consortium to establish the definition, diagnosis, and treatment for oligometastasis. Two large phase 3 studies are ongoing to evaluate the survival outcomes of patients with oligometastasis treated with perioperative chemotherapy combined with surgical removal. The concept of oligometastasis is not yet fully established in the field of gastric cancer. However, metastatic lesions that are localized, technically resectable at diagnosis, present a certain response to preoperative chemotherapy, and present favorable survival outcomes with local treatments, sometimes in combination with chemotherapy, are recognized as oligometastasis in the field of gastric cancer. Oligometastasis is noted in European Society for Medical Oncology guidelines and Japanese gastric cancer treatment guidelines, and local treatment is mentioned as one of the pivotal treatment options for oligometastasis. Solitary liver metastasis or a small number of liver metastases; retroperitoneal lymph node metastasis, especially localized para-aortic lymph node metastasis; localized peritoneal dissemination; and Krukenberg tumor are representative types of oligometastasis in gastric cancer. The AIO-FLOT3 trial prospectively evaluated the efficacy of multimodal treatments for gastric cancer with oligometastasis, including surgical resection of primary and metastatic lesions combined with chemotherapy, confirming favorable survival outcomes. Two phase 3 studies are ongoing to investigate the efficacy of surgical resection combined with perioperative chemotherapy compared with palliative chemotherapy. Thus far, the evidence suggests that multimodal treatment for oligometastasis of gastric cancer is promising. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer remains the world's fifth most lethal malignancy. Perineural invasion (PNI) is a common growth pattern of gastric cancer. Currently, the diagnosis of PNI relies on postoperative pathology, which is an invasive approach. In this study, we built a radiomics–clinicopathological model based on logistic regression analysis to preoperatively predict PNI. The radiomics–clinicopathological model yielded AUC values of 0.851 (95%CI: 0.769–0.933) in the training set, 0.842 (95%CI: 0.713–0.970) in the testing set and 0.813 (95%CI: 0.672–0.954) in the validation set. This proposed model may help clinicians make clinical decisions and provide personalized treatment to gastric cancer patients. In this research, the value of perineural invasion (PNI) in predicting prognoses for gastric cancer patients was also studied. Purpose: The aim of this study was to construct and validate a nomogram for preoperatively predicting perineural invasion (PNI) in gastric cancer based on machine learning, and to investigate the impact of PNI on the overall survival (OS) of gastric cancer patients. Methods: Data were collected from 162 gastric patients and analyzed retrospectively, and radiomics features were extracted from contrast-enhanced computed tomography (CECT) scans. A group of 42 patients from the Cancer Imaging Archive (TCIA) were selected as the validation set. Univariable and multivariable analyses were used to analyze the risk factors for PNI. The t-test, Max-Relevance and Min-Redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select radiomics features. Radscores were calculated and logistic regression was applied to construct predictive models. A nomogram was developed by combining clinicopathological risk factors and the radscore. The area under the curve (AUC) values of receiver operating characteristic (ROC) curves, calibration curves and clinical decision curves were employed to evaluate the performance of the models. Kaplan–Meier analysis was used to study the impact of PNI on OS. Results: The univariable and multivariable analyses showed that the T stage, N stage and radscore were independent risk factors for PNI (p < 0.05). A nomogram based on the T stage, N stage and radscore was developed. The AUC of the combined model yielded 0.851 in the training set, 0.842 in the testing set and 0.813 in the validation set. The Kaplan–Meier analysis showed a statistically significant difference in OS between the PNI group and the non-PNI group (p < 0.05). Conclusions: A machine learning-based radiomics–clinicopathological model could effectively predict PNI in gastric cancer preoperatively through a non-invasive approach, and gastric cancer patients with PNI had relatively poor prognoses. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers of the esophagus and stomach are among the most common and deadly cancers worldwide, and have been major contributors to human suffering throughout recorded history. This review traces the chronology of these cancers from 3000 BCE to the present. The first several thousand years were devoted to palliative operations, before advances in operative technique and technology led to the first curative surgery in 1913. Around the same time, in 1910, systemic therapies were introduced, and radiotherapy shortly thereafter. The later decades of the 20th century saw a groundswell of advances in surgery, endoscopic therapy, systemic therapy, and radiotherapy, and, from the 1970s, an increasing focus on combination approaches. While studies in these areas continued to advance, immunotherapies became a major new category in the late 2010s. An increasing number of immunotherapies have been developed and now encompass more indications and earlier lines of therapy. As standards of care incorporate these effective yet expensive therapies, care must be given to disparities and methods for increasing access. Esophagogastric cancers are among the most common and deadly cancers worldwide. This review traces their chronology from 3000 BCE to the present. The first several thousand years were devoted to palliation, before advances in operative technique and technology led to the first curative surgery in 1913. Systemic therapies were introduced in 1910, and radiotherapy shortly thereafter. Operative technique improved massively over the 20th century, with operative mortality rates reducing from over 50% in 1933 to less than 5% by 1981. In addition to important roles in palliation, endoscopy became a key nonsurgical curative option for patients with limited-stage disease by the 1990s. The first nonrandomized studies on combination therapies (chemotherapy ± radiation ± surgery) were reported in the early 1980s, with survival benefit only for subsets of patients. Randomized trials over the next decades had similar overall results, with increasing nuance. Disparate conclusions led to regional variation in global practice. Starting with the first FDA approval in 2017, multiple immunotherapies now encompass more indications and earlier lines of therapy. As standards of care incorporate these effective yet expensive therapies, care must be given to disparities and methods for increasing access. [ABSTRACT FROM AUTHOR]