Gastric cancer (GC) is a highly heterogeneous disease, and the response of patients to clinical treatment varies substantially. There is no satisfactory strategy for predicting curative effects to date. We aimed to explore a new method for predicting the clinical efficacy of GC treatment based on immune variables detected via flow cytometry.

We collected 394 tumour tissues from GC patients for flow cytometry analysis and gating analysis of tumour-infiltrating immune cells (TIICs). Unsupervised consensus clusters were generated from the cohort to classify patients into different phenogroups, and their clinical characteristics were examined. The derived model was evaluated via principal component analysis and t-distributed stochastic neighbourhood embedding analysis. Kaplan-Meier's curves were used to determine the prognosis during a 920-day-long median follow-up period (interquartile range: 834-1071 days). Adjusted multivariate Cox regression analysis was used to evaluate the association of clusters with disease-free survival (DFS) and recurrence.

All patients were classified based on their TIIC profiles into the C1 (characterized by low CD45 negative cell, high lymphocyte, high neutrophil and low CD3 + T cell levels), C2 (characterized by high CD8 + CD279+ cell and low CD4+ Th and CD8+ Tc cell numbers) and C3 (characterized by high CD4 + CD25+ and Treg cell levels) phenogroups. Patients from the three clusters had varied pathologies, MMR statuses and TIIC distribution patterns (p < .05). Kaplan-Meier's analysis showed that the prognosis of C3 was inferior compared to C1 and C2 (p = .0025). Adjusted Cox proportional hazard models helped us identify that C1 and C2 exhibited a favourable factor of recurrence after surgery, compared to C3. Kaplan-Meier's analysis showed that C1 and C2 were associated with a better DFS than C3 in some GC patient subgroups.

The machine learning model developed was found to be effective model at predicting the prognosis of patients with GC and their TIIC profiles for risk stratification in clinical settings.

Due to constant stimulation by stomach acid and local bleeding, gastric tissue wounds tend to heal slowly and complications such as anastomotic leakage have a high incidence. Suturing is often used to treat gastric wounds in clinic, but it still faces risks such as bleeding, slow healing, and leakage. Recently, hydrogel have been widely used to treat various types of wounds. Although hydrogels have shown promising efficacy in wound healing, it is still a challenge in dealing with wounds in gastric tissue for the poor adaptability of traditional materials in acidic environments. Hence, a series of pH responsive and good tissue adhesive hydrogels (MA-HA/AA) based on methacryloyl hyaluronic acid (MA-HA) and acryloyl-6-aminocaproic acid (AA) via in situ photo-crosslinking were designed, and anti-inflammatory and pro-healing traditional Chinese medicines ginsenoside Rg1 was incorporated into the hydrogel to treat gastric tissue wound. These acid-responsive hydrogels could form effective acid-resistant barriers and could lead to hemostasis rapidly through its strong adhesion. Besides, the hydrogels contracted under an acidic environment, which could tighten the gastric tissue wounds and sustained release the loaded ginsenoside Rg1. In addition, the hydrogels showed excellent biocompatibility and in vivo degradability. In summary, the acid-responsive contractile hyaluronic acid hydrogel loaded with ginsenoside Rg1 had good properties for hemostasis and acid-resistance to facilitate the promotion of gastric wounds healing.

HER2 overexpression is a marker for targeted therapy in adenocarcinoma of the gastroesophageal junction (GEJ) and stomach. The present study aimed to evaluate the frequency of HER2 overexpression with reference to clinicopathological characteristics in subjects from King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 10-year period. A retrospective cross-sectional study was conducted on all biopsy and resection specimens diagnosed with either gastric cancer (GC) or GEJ adenocarcinomas from patients between January 2014 and December 2023 that had a final pathology report. Demographic characteristics of 122 patients, including age and sex, were collected, along with pathological details such as tumor grade, histological subtype and HER2 status. χ2 test was used to analyze the association between collected clinicopathological characteristics and HER2 status of the tumor. Most patients were aged 40-60 years. Males constituted 66% of the patients, and the ethnic distribution between Saudi and non-Saudi was almost equal. The most common subtype of cancer was the intestinal type (49%), and the majority of cases were poorly differentiated (64%). HER2 status was assessed in only 61% of cases, with 13.5% showing gene amplification. There was no significant association found between HER2 status and clinicopathological features.

Triple-negative breast cancer (TNBC) is the most frequent malignancy in women. It is a prevalent condition, representing 15-20 % of all breast cancer cases, characterized by its aggressive subtype and unfavorable prognosis.

The main aim of this study is to find and develop a potential novel therapeutic candidate for TNBC treatment utilizing luteolin derivatives compounds.

In this study, we used the stable TNBC protein structure from the Protein Data Bank (PDB) and selected luteolin, a bioactive compound known for its anti-cancer properties, to design potential anti-cancer drugs using computational methods. Structural activity relationship methodologies were used to evaluate active and inactive outcomes using pass prediction scores. Furthermore, we employed in-silico methods such as ADMET, drug-likeness evaluation, DFT quantum calculations, and Frontier Molecular Orbitals (HOMO and LUMO). Afterwards, we performed molecular docking for binding affinity and molecular dynamics simulations over 200 ns to validate interactions with TNBC protein RESULTS: Our results demonstrated that the ligands DM02, DM06, DM07, and DM09 did not violate Lipinski rules, and their reduced HOMO-LUMO energy gap indicates enhanced chemical reactivity and interaction with biological targets. The drug's maximum softness and minimum hardness values showed rapid metabolism and no hepatotoxicity, carcinogenicity, skin sensitization, or aquatic toxicity. Molecular docking studies revealed that DM02 and DM09, luteolin derivatives, have the highest binding affinity with the TNBC protein (PDB ID 5HA9) and our study confirms their stable interactions with the protein, suggesting potential therapeutic agents for TNBC.

Our computational data suggest that Luteolin derivatives have the potential to be utilized as therapeutic agents for TNBC. However, further experimental validation is needed to validate these findings.

Antibody-drug conjugates, particularly trastuzumab deruxtecan (T-DXd), have emerged as effective therapies for various solid tumours. Clinical trials show that T-DXd improves survival in both HER2-positive and HER2-low breast cancer patients. Additionally, it improves survival in HER2-positive gastro-oesophageal cancer and elicits objective responses in HER2-low tumours. Responses have also been noted in lung and gynaecological cancers with HER2 expression, although subgroup analyses for HER2-low cases are lacking. This review assesses HER2 protein expression levels and gene amplification across solid tumours where T-DXd shows potential benefits. We focus on the accuracy and limitations of HER2 testing methods, particularly for identifying HER2-low cancer. A semi-systematic approach was employed, searching EMBASE, Medline, Cochrane, and PubMed databases. We calculated median incidences of HER2-positive, HER2-low, and HER2-0 by immunohistochemistry (IHC), and HER2 amplification by in situ hybridisation (ISH). A total of 144 studies were included, covering breast (n=57), gastro-oesophageal (n=33), lung (n=17), gynaecological (n=24), and various other carcinomas (n=13). The median incidences of HER2-low were 52%, 16%, 58%, and 17% in breast, gastro-oesophageal, endometrial, and ovarian cancers, respectively, with unknown incidences in lung and cervical cancers. Factors influencing HER2-low detection include tumour heterogeneity, antibody clones, observer variability, and lack of validated scoring criteria. Given the significant proportion of HER2-low cases, many patients could benefit from T-DXd, but limitations in detection accuracy necessitate further research and standardisation in diagnostic methods and criteria to advance the clinical utility of T-DXd for HER2-low tumours.

Cellular metabolic reprogramming supports tumor proliferation, invasion, and metastasis by enhancing resistance to stress and immune clearance. Understanding these metabolic changes within the tumor microenvironment is vital to developing effective therapies. We conducted single-cell RNA sequencing on 11 gastric cancer (GC) samples and eight metastatic lesions, analyzing 92,842 cells across eight cell types, including cancer cells, stromal cells, and immune cells. Our findings highlight that the mitochondrial ATP synthase subunit ATP5MC2 uniquely alters during early GC metastasis. Experiments and clinical data confirmed that ATP5MC2 upregulation facilitates cancer cell proliferation, invasion, and metastasis. Constructing a single-cell atlas revealed significant immune cell heterogeneity associated with GC metastasis and its molecular subtypes. This study underscores the role of ATP5MC2-driven metabolic changes and diverse immune landscapes in promoting GC metastasis, offering new avenues for anti-metastatic treatment development.

The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus (EBV), the first virus confirmed to cause human cancer. Viral infections significantly contribute to the global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B virus (HBV), human papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. These viruses are primarily associated with hepatocellular carcinoma, gastric cancer, cervical cancer, nasopharyngeal carcinoma, Kaposi sarcoma, lymphoma, and adult T-cell leukemia/lymphoma. Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers, providing new targets and strategies for treatment or prevention. This review first outlines the global epidemiology of virus-related tumors, milestone events in research, and the process by which oncogenic viruses infect target cells. It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly, including the regulation of oncogenes or tumor suppressor genes, induction of genomic instability, disruption of regular life cycle of cells, immune suppression, chronic inflammation, and inducing angiogenesis. Finally, current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.

The aim of this study was to compare the effects of accommodated jejunal interposition double tract reconstruction (aji-DTR) and Roux-en-Y reconstruction after laparoscopic-assisted total gastrectomy on intraoperative and postoperative indicators in advanced gastric cancer (AGC) patients.

A retrospective analysis was performed on 80 AGC patients, including 43 with aji-ATR and 37 with Roux-en-Y reconstruction. Propensity score matching was performed between the two groups. The primary outcome measures included operative time, intraoperative blood loss, postoperative complications, postoperative hospital stay, total hospitalization costs, and survival rate. The secondary outcome measures were postoperative nutritional status, recovery of digestive function, and postoperative gastrointestinal·symptoms.

There were 24 pairs of patients after matching. There were no significant differences in the operative time, intraoperative blood loss, time of first flatus, time of first defecation, time of liquid diet, time of semi-liquid diet, postoperative complications, postoperative hospital stays, and total hospitalization costs (all P > 0.05). Interestingly, Roux stasis syndrome was significantly more frequent in Roux-en-Y group than aji-DTR group [6 (25.0%) vs 1 (4.2%), P = 0.045]. While no significant difference was observed in survival rates, reflux esophagitis, dumping syndrome and nutritional parameter including hemoglobin, albumin, and prognostic nutritional index (all P > 0.05).

Compared with Roux-en-Y reconstruction, aji-DTR had similar surgical parameters, postoperative digestive function recovery, nutritional parameters, and survival rate, but showed an advantage in reducing Roux stasis syndrome. Therefore, aji-DTR after laparoscopic assisted total gastrectomy may be a safe and feasible alternative for AGC patients.

In the current period of pharmaceutical discovery, herbal remedies have shown to be an unmatched supply of anticancer medications. Plants and their derivatives, through analogues, play a vital role in cancer treatment.

The current investigation assessed the effectiveness of inhibiting the growth of gastric cancer cells in AGS cells by blocking the JAK/ STAT3 signalling pathways using the natural medicines Concanavalin A (Con-A) and silibinin (SB).

After being exposed to various doses of concanavalin A, and silibinin (Con-A + SB) for 24 h (0- 60 µM), the cells were evaluated for multiple studies. The MTT assay was used to examine the combination of Con-A + SB-induced cytotoxicity. To evaluate ROS, DCFH-DA staining was utilized. Dual (AO/EtBr) staining was performed to examine apoptotic modifications, and MMP levels in AGS cells were examined using the appropriate fluorescence staining assays. By using flow cytometry and western blotting, cell cycle, and apoptosis were assessed.

The relative cytotoxicity of Con-A and SB was found to be approximately 19.6 μM and 16.78 μM, (p < 0.05) correspondingly, according to the findings. After a 24-h incubation period, the combination of Con-A and SB generates significant cytotoxicity in AGS cells, with an IC50 of 10.37 μM (p < 0.01). Furthermore, AGS cells treated with Con-A and SB concurrently showed increased apoptotic signals, exhibited by Bax overexpression, Bcl-2 downregulation, and Caspase-3 activation, as well as considerable ROS generation.

Therefore, the combination usage of Con-A + SB has the potential to serve as a chemotherapeutic agent since it prevents the synthesis of JAK/STAT3 intermediated control of proliferation and cell cycle-regulating proteins.

This study aimed to develop an intelligent individualized nutrition management (iNutrition) applet for postdischarge gastric cancer patients following gastrectomy based on the Health Action Process Approach (HAPA) theory and using the design thinking method.

We developed the iNutrition applet using the design thinking method, including the following phases: (1) "empathize and define," which focused on understanding patients' needs and establishing the goals of the iNutrition applet through qualitative interviews; (2) "ideate and prototype," during which literature reviews and multidisciplinary interactive workshops to conceptualize innovative solutions were conducted and a fully functional iNutrition applet was developed; and (3) "test," during which the iNutrition applet was evaluated through usability testing.

Based on qualitative interviews with 15 patients, we determined that the iNutrition applet would need to satisfy patients' needs in the following areas: adjustment to postoperative anatomical changes, evidence-based knowledge, communication with peers, consultation with medical staff, tailored nutritional plans, coping plans, and needs for technology. Consequently, the applet was designed to have eight functions: gastrointestinal symptom management, nutrition knowledge, medical consultation, peer communication, nutrition goals, nutrition diary with calculator, weekly meal plan, and nutritional status score. During short-term usability testing, the patients' task completion rate ranged from 88 to 100%. Long-term usability testing resulted in a System Usability Scale (SUS) score of 75.20 ± 10.63 and a net promoter score (NPS) of 32%. The participants were generally satisfied with the applet's design and functionality, providing feedback that informed further refinements to the final version of the applet.

The iNutrition applet, which has received high ratings for usability and user satisfaction, is an acceptable and feasible method of postdischarge nutritional management for gastric cancer patients following gastrectomy.

Previous trials have revealed better treatment efficacy of programmed cell death 1 (PD-1) inhibitors combined with chemotherapy as first-line treatments than chemotherapy alone in advanced gastric cancer (GC) patients, but real-world evidence is still lacking. Hence, this real-world study aimed to investigate the efficacy and safety of PD-1 inhibitors plus chemotherapy as first-line treatments compared with chemotherapy alone in advanced GC patients.

In total, 102 advanced GC patients were allocated into a combination group (receiving chemotherapy combined with a PD-1 inhibitor as a first-line treatment) (n = 48) or a chemotherapy group (receiving chemotherapy only as a first-line treatment) (n = 54) according to their actual treatment regimens.

The objective response rate (ORR) was greater in the combination group than in the chemotherapy group (25.0 % versus 9.3 %, P = 0.033), whereas the disease control rate (DCR) was not different between the groups (83.3 % versus 66.7 %, P = 0.054). Progression-free survival (PFS) was prolonged in the combination group than in the chemotherapy group (P = 0.018). The median (95 % confidence interval) PFS was 19.7 (12.2-27.2) months in the combination group and 16.5 (7.3-25.7) months in the chemotherapy group. Multivariate logistic regression analyses revealed that PD-1 inhibitors combined with chemotherapy were independently associated with an increased ORR (odds ratio: 4.180, P = 0.024), increased DCR (odds ratio: 2.928, P = 0.049), and prolonged PFS (hazard ratio: 0.388, P = 0.030). No difference was found in total or each specific grade III-IV adverse reaction between the groups (all P > 0.05).

Treatment with a PD-1 inhibitor plus chemotherapy as a first-line treatment shows better treatment efficacy with similar safety to that of chemotherapy alone in advanced GC patients.

The objective is to systematically gather relevant research to determine and quantify the risk factors and pooled prevalence for pneumonia after a radical gastrectomy for gastric cancer.

The reporting procedures of this meta-analysis conformed to the PRISMA 2020. Chinese Wan Fang data, Chinese National Knowledge Infrastructure (CNKI), Chinese Periodical Full-text Database (VIP), Embase, Scopus, CINAHL, Ovid MEDLINE, PubMed, Web of Science, and Cochrane Library from inception to January 20, 2024, were systematically searched for cohort or case-control studies that reported particular risk factors for pneumonia after radical gastrectomy for gastric cancer. The pooled prevalence of pneumonia was estimated alongside risk factor analysis. The quality was assessed using the Newcastle-Ottawa Scale after the chosen studies had been screened and the data retrieved. RevMan 5.4 and R 4.4.2 were the program used to perform the meta-analysis.

Our study included data from 20,840 individuals across 27 trials. The pooled prevalence of postoperative pneumonia was 11.0% (95% CI = 8.0% ~ 15.0%). Fifteen risk factors were statistically significant, according to pooled analyses. Several factors were identified to be strong risk factors, including smoking history (OR 2.71, 95% CI = 2.09 ~ 3.50, I2 = 26%), prolonged postoperative nasogastric tube retention (OR 2.25, 95% CI = 1.36-3.72, I2 = 63%), intraoperative bleeding ≥ 200 ml (OR 2.21, 95% CI = 1.15-4.24, I2 = 79%), diabetes mellitus (OR 4.58, 95% CI = 1.84-11.38, I2 = 96%), male gender (OR 3.56, 95% CI = 1.50-8.42, I2 = 0%), total gastrectomy (OR 2.59, 95% CI = 1.83-3.66, I2 = 0%), COPD (OR 4.72, 95% CI = 3.80-5.86, I2 = 0%), impaired respiratory function (OR 2.72, 95% CI = 1.58-4.69, I2 = 92%), D2 lymphadenectomy (OR 4.14, 95% CI = 2.29-7.49, I2 = 0%), perioperative blood transfusion (OR 4.21, 95% CI = 2.51-7.06, I2 = 90%), and hypertension (OR 2.21, 95% CI = 1.29-3.79, I2 = 0%). Moderate risk factors included excessive surgery duration (OR 1.51, 95% CI = 1.25-1.83, I2 = 90%), advanced age (OR 1.91, 95% CI = 1.42-2.58, I2 = 94%), nutritional status (OR 2.62, 95% CI = 1.55-4.44, I2 = 71%), and history of pulmonary disease (OR 1.61, 95% CI = 1.17-2.21, I2 = 79%).

This study identified 15 independent risk factors significantly associated with pneumonia after radical gastrectomy for gastric cancer, with a pooled prevalence of 11.0%. These findings emphasize the importance of targeted preventive strategies, including preoperative smoking cessation, nutritional interventions, blood glucose and blood pressure control, perioperative respiratory training, minimizing nasogastric tube retention time, and optimizing perioperative blood transfusion strategies. For high-risk patients, such as the elderly, those undergoing prolonged surgeries, experiencing excessive intraoperative blood loss, undergoing total gastrectomy, or receiving open surgery, close postoperative monitoring is essential. Early recognition of pneumonia signs and timely intervention can improve patient outcomes and reduce complications.

The early prediction of lymph node positivity (LN+) after neoadjuvant chemotherapy (NAC) is crucial for optimizing individualized treatment strategies. This study aimed to integrate radiomic features and clinical biomarkers through machine learning (ML) approaches to enhance prediction accuracy by focusing on patients with locally advanced gastric cancer (LAGC).

We retrospectively enrolled 277 patients with LAGC and randomly divided them into training (n = 193) and validation (n = 84) sets at a 7:3 ratio. In total, 1,130 radiomics features were extracted from pre-treatment portal venous phase computed tomography scans. These features were linearly combined to develop a radiomics score (rad score) through feature engineering. Then, using the rad score and clinical biomarkers as input features, we applied simple statistical strategies (relying on a single ML model) and integrated statistical strategies (including classification model integration techniques, such as hard voting, soft voting, and stacking) to predict LN+ post-NAC. The diagnostic performance of the model was assessed using receiver operating characteristic curves with corresponding areas under the curve (AUC).

Of all ML models, the stacking classifier, an integrated statistical strategy, exhibited the best performance, achieving an AUC of 0.859 for predicting LN+ in patients with LAGC. This predictive model was transformed into a publicly available online risk calculator.

We developed a stacking classifier that integrates radiomics and clinical biomarkers to predict LN+ in patients with LAGC undergoing surgical resection, providing personalized treatment insights.

Neoadjuvant therapy (NAT) is increasingly used in locally advanced gastric cancer (LAGC), but a significant proportion of patients respond poorly, causing adverse outcomes. Few studies have specifically examined the prognosis of this subgroup. This study aimed to analyze survival and recurrence in poor responders to guide follow-up and treatment strategies.

This multicenter retrospective study included patients with LAGC who received NAT. Tumor regression was graded following the Becker system, defining TRG 2-3 as poor response. Outcomes were assessed for overall survival (OS), recurrence-free survival (RFS), and recurrence patterns.

648 patients were included: 341 with TRG 2 and 307 with TRG 3. In the entire cohort, the 3-year OS and RFS were 54.6% and 55.2%, respectively. Recurrence occurred in 299 patients, with the following recurrence patterns: distant metastasis (26.1%, n = 78), peritoneal metastasis (21.1%, n = 63), locoregional recurrence (18.7%, n = 56), and multiple-site recurrence (18.4%, n = 55). Liver metastasis was significantly higher in the TRG 3 group than in the TRG 2 group (14.1% versus 5.3%, P = 0.010). ypN+ was the most significant independent risk factor for recurrence (OR = 2.73, 95% CI 1.83-4.08, P < 0.001); an increasing number of positive lymph nodes led to higher 3-year cumulative mortality in patients. Despite poor response to NAT, completing over four adjuvant chemotherapy cycles was associated with improved survival outcomes.

Poor NAT responders in LAGC have high recurrence rates, particularly in the first year post-surgery, with ypN+ status being the strongest predictor of recurrence. Completing over four cycles of AC was associated with survival improvement in this group.

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide. While laparoscopic gastrectomy (LG) has been widely adopted for early and locally advanced gastric cancer (AGC), its safety and oncological efficacy in T4a GC remain unclear. To date, no randomized controlled trials have specifically examined the role of LG in the treatment of T4a GC. This study aims to provide robust evidence comparing the short- and long-term outcomes of laparoscopic distal gastrectomy (LDG) versus open distal gastrectomy (ODG) in resectable T4a GC.

This is a phase III, randomized controlled, non-inferiority trial. Patients with clinical T4a GC (cT4aN0-3M0) suitable for distal gastrectomy with D2 dissection will be randomly assigned in a 1:1 ratio to undergo either LDG or ODG. A total 240 patients (120 each group) are required to statistically show non-inferiority of the LDG with respect to the primary end-point, 3-years disease-free survival (DFS). Secondary endpoints include morbiity, mortality, postoperative recovery, and quality of life.

This study is the first prospective randomized trial specifically designed to compare laparoscopic and open approaches for T4a GC. By standardizing surgical techniques and ensuring experienced surgeons perform the procedures, this trial aims to establish whether LDG can provide equivalent oncological outcomes while reducing perioperative morbidity and enhancing postoperative recovery. The findings will provide high-quality evidence to inform future guidelines and clinical decision-making in the management of T4a gastric cancer.

This study is registered at ClinicalTrials.gov (NCT04384757), version 6. Registration Date: 08/05/2020.

In this prospective, open-label, exploratory study (RENMIN-213), patients with previously untreated, HER2-negative, advanced G/GEJ adenocarcinoma with signet ring cell carcinoma or peritoneal metastasis were enrolled to receive eight cycles of apatinib, tislelizumab, and chemotherapy every 3 weeks, with a maintenance therapy with apatinib plus tislelizumab for a maximum of 1 year. Homogeneous patients receiving immune checkpoint inhibitors combined with chemotherapy at the same time were deemed as the control group for efficacy. The primary endpoint was progression-free survival. Secondary endpoints were objective response rate, disease control rate, duration of response, overall survival, biomarkers, health-related quality of life, and safety. A total of 33 patients [median (range) age, 60 (32-72) years; 21 (63.6%) male; 11 (33.3%) signet ring cell carcinoma; 30 (90.9%) peritoneal metastasis] were enrolled and deemed evaluable for efficacy analysis. Of these patients, 32 (97%) were without disease progression, of whom 1 (3.0%) patient had complete response and 18 (54.6%) had partial response. Six patients (18.2%) were able to undergo surgery after treatment. After propensity score matching, the median progression-free survival was 10.17 months (95% confidence interval, 7.13-13.21) in the apatinib combined with tislelizumab and chemotherapy group, as compared with 6.0 months in the immune checkpoint inhibitor combined with chemotherapy group. The median duration of response increased from 4.5 to 8.7 months. The objective response rate increased from 33.3% to 54.6%, and the disease control rate increased from 87.9% to 97.0%. Treatment-related grade 3 or higher adverse events for evaluable patients occurred in 11 patients (33.3%), and patients' health-related quality of life improved after treatment.

To evaluate the efficiency of 68Ga-FAPI-04 PET (PET/MRI or PET/CT) for N and M staging in gastric carcinoma and compare outcomes with histopathology and contrast-enhanced computed tomography (CECT).

Patients with gastric carcinoma who had undergone 68Ga-FAPI-04 PET/MRI or PET/CT before treatment were retrospectively enrolled. Histopathology post lymphadenectomy was the gold standard for N staging, while histopathology and follow-up data were the reference for overall outcomes. The diagnostic efficiency of 68Ga-FAPI-04 PET for detecting regional lymph node involvement and distant metastases was compared to that of CECT.

Sixty-two patients were enrolled. In 18 patients who underwent 68Ga-FAPI-04 PET/MRI and lymphadenectomy, 532 lymph nodes were dissected. 68Ga-FAPI-04 PET/MRI showed similar sensitivity, specificity, and accuracy compared to CECT (28.3% vs. 23.2%, 99.8% vs. 99.3%, and 86.5% vs. 85.2%, all P > 0.05). Fifty-five patients had regional lymph node metastasis, 68Ga-FAPI-04 PET exhibited comparable diagnostic efficiency to CECT, with sensitivity of 83.6% versus 87.3%, specificity of 100% versus 85.7%, accuracy of 85.5% versus 87.1% (all P > 0.05). Excluding 3 patients with only abdominal CECT, 32 out of 59 patients had distant metastasis, with no significant differences in sensitivity, specificity, and accuracy between 68Ga-FAPI-04 PET and CECT based on patient (100% vs. 87.5%, 92.6% vs. 96.3%, and 96.6% vs. 91.5%, all P >0.05). Notably, 68Ga-FAPI-04 PET outperformed CECT in detecting peritoneal, distant lymph nodes, bone, liver, and ovarian metastases by visualizing more lesions or greater lesion extent.

68Ga-FAPI-04 PET exhibits comparable diagnostic performance to CECT for patient-based N staging and M staging of gastric cancer. However, it surpasses CECT in visualizing distant metastases.

To investigate the value of radiomic analysis of dual-energy CT (DECT)-derived iodine maps (IMs) for the differentiation between T1/2 and T3/4a stage tumors in gastric cancer (GC).

A total of 263 patients who received upfront surgery and were pathologically confirmed with gastric adenocarcinoma were enrolled in this study. Dual-phase enhanced CT scans with gemstone spectral imaging (GSI) mode were performed within two weeks before surgery. 151 patients were retrospectively collected for the training (n = 105) and validation (n = 46) cohorts, and 112 patients were prospectively collected for the external test1 (n = 68) and external test2 (n = 44) cohorts. According to the postoperative pathological T stage, patients were classified into T1/2 and T3/4a stage groups. Clinical characteristics were recorded and quantitative iodine concentration (IC) of tumors was measured. Radiomics features were extracted from the venous phase (VP) IMs by three-dimensional region of interest (3D-ROI) segmentation. Feature selection was performed using the least absolute shrinkage and selection operator. Four machine learning algorithms, including random forest, logistic regression, naive Bayes, and support vector machine, were used to construct radiomics models. Finally, the most valuable clinical characteristics, DECT parameters, and the best radiomics model were combined to build a nomogram. The diagnostic performance of nomogram was evaluated by the area under receiver operating characteristic curve (AUC), calibration curve, and decision curve.

The nomogram combined tumor clinical T stage (cT), tumor thickness, venous-phase iodine concentration (ICVP), normalized arterial-phase iodine concentration (nICAP), and Radscore (derived from logistic regression model). This integrated model demonstrated favorable performance in the differentiation between T1/2 and T3/4a stage tumors in GC, with AUCs of 0.892 (95 %CI: 0.829-0.956), 0.846 (95 %CI: 0.734-0.958), 0.894 (95 %CI: 0.818-0.970) and 0.821 (95 %CI: 0.689-0.952) observed for the training, validation, external test 1, and external test 2 cohorts, respectively. Hosmer-Lemeshow test showed a good fit (all P > 0.05). Decision curves confirmed that the nomogram provided more net clinical benefit than the default simple strategy over a wide range of threshold probabilities.

We have developed and validated a multidimensional personalized nomogram that integrates a radiomics model based on DECT-derived IMs, DECT quantitative parameters, and traditional clinical features. The proposed model demonstrated favorable performance in preoperative identification of T3/4a stage tumors in GC.

Gastric cancer (GC) represents a global health-care challenge. Recent progress in immunotherapy has elicited attracted considerable attention as a viable treatment option through modulating the host immune system and unleashing pre-existing immunity, which has profoundly revolutionized oncology, especially GC. Nonetheless, low clinical response and intrinsic and acquired resistance remain persistently challenging. The microenvironment of GC comprising multifarious stromal cell types has remarkable immunosuppressive elements that may impact the efficacy of immunotherapy. Immunosenescence is increasingly regarded as a factor that contributes to cancer development, remodels the tumor microenvironment and affects the efficacy of immunotherapy. Natural products are at the forefront of traditional medicine. Senotherapeutics is a class of drugs and natural products capable of delaying, preventing, or reversing the senescence process (i.e., senolytics) or suppressing senescence-associated secretory phenotype (i.e., senomorphics). Emerging evidence supports that natural products can improve the efficacy of existing immunotherapy and expand their indications in GC mainly based upon remodeling the immunosuppressive microenvironment and reversing immunosenescence. The review provides an integrated review of previously reported and ongoing clinical trials with immunotherapeutic regimens in GC and discusses current challenges. Next, we focus on natural compounds that exert anti-GC functions and possess immunomodulatory properties. More attention is paid to the potential of these natural compounds in modulating the immune microenvironment and immunosenescence. Lastly, we discuss the nanomedicine that can overcome the deficiencies of natural products. Altogether, our review suggests the enormous potential of natural compounds in GC immunotherapy, and provides an important direction for future research.

This study tested the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in restaging locally advanced gastric cancer after neoadjuvant therapy (NAT) using pathologic T stage (ypT) and pathologic N stage (ypN) as the reference standard.

Between August 2022 and September 2023, the study enrolled a prospective cohort of 70 gastric cancer patients who underwent NAT and subsequent surgical resection. MRI procedures, including DLSB T2-weighted imaging (T2WI), ZOOMit diffusion-weighted imaging (DWI), and XD-VIBE dynamic contrast-enhanced imaging (DCE), were performed after NAT and before surgery. Four abdominal radiologists independently assigned radiologic T stage (yrT) and radiologic N stage (yrN) based on individual and combined sequences. Inter-reader agreement was quantified using Kendall's coefficient. Diagnostic accuracy was determined by comparing MRI assessments and pathologic outcomes, with pairwise comparisons analyzed via the McNemar test. Subgroup analysis evaluated the performance in identifying good responders to NAT.

Inter-reader agreement was almost perfect for T restaging and substantial for N restaging. Diagnostic accuracy for T restaging was 0.432 using DLSB-T2WI, 0.586 using ZOOMit DWI, 0.557 using XD-VIBE DCE, and 0.586 using mpMRI. The accuracy demonstrated by DWI, DCE and mpMRI was superior to that of T2WI (all P < 0.05). For N restaging, the accuracy of the mpMRI protocol was 0.443. Notably, mpMRI achieved an AUC of 0.879 (95% confidence interval 0.835-0.915) for differentiating ypT0-1 tumors.

Advanced mpMRI strategies can serve as a valuable tool for restaging gastric cancer after NAT. Accurately differentiating good responders to neoadjuvant therapy through mpMRI holds significant clinical implications for personalized treatment strategies and improved patient outcomes.

Although neoadjuvant therapy (NAT) for advanced gastric cancer (AGC) can benefit patient survival, few studies have compared the short- and long-term outcomes of robotic and laparoscopic gastrectomy for AGC after NAT.

The clinical data of 321 AGC patients who received NATs and who underwent robotic gastrectomy (RG, n = 109) or laparoscopic gastrectomy (LG, n = 212) between May 2017 and September 2022 were collected and analyzed retrospectively at our center. After propensity score matching (PSM) for 1:1 matching to eliminate bias, both groups had 106 cases. Short-term clinical outcomes and long-term survival-related indicators were compared between the two groups of patients.

A total of 212 patients were included in the groups after matching. There were fewer overall complications (13.2% vs. 28.3%, P = 0.007) and surgical complications (8.5% vs. 17.9%, P = 0.043) in the RG group than in the LG group. Compared with the LG group, the RG group had more harvested overall lymph nodes (35.25 ± 4.99 vs. 31.45 ± 6.31, P < 0.001) and more suprapancreatic lymph nodes (13.12 ± 4.38 vs. 10.05 ± 4.13, P < 0.001). Patients in the RG group had significantly shorter surgery times (217.62 ± 47.49 vs. 267.25 ± 70.68, P < 0.001) and less blood loss (46.51 ± 27.02 vs. 70.75 ± 37.25, P < 0.001) than patients in the LG group. The RG group had significantly faster bowel function recovery, earlier liquid diet, and shorter hospital stay. Compared with LG, RG had a better 3-year RFS (75.5% vs. 62.3%, P = 0.017).

Compared with laparoscopic surgery, robotic surgery significantly increased the number of lymph node dissected, reduced intraoperative blood loss, and postoperative surgical complications rate. Although RG did not statistically improve 3-year overall survival, there was a significant improvement in RFS and could be an alternative surgical method for GC patients after NAC.

Gastric cancer patients without invasion of the squamocolumnar junction have a low probability of extragastric mesenteric metastasis, and the survival benefit of conducting D2 lymphadenectomy plus complete mesogastrium excision is unclear in this group of patients.

This was a retrospective analysis of patients with stage II/III gastric cancer without invasion of the squamocolumnar junction who underwent laparoscopic radical surgery for gastric cancer at the First Hospital of Putian City, Fujian Province, from January 2014 to May 2019. Five-year disease-free survival was the primary outcome, and 5-year overall survival and the recurrence pattern were the secondary outcomes. Morbidity, mortality, and surgery-related outcomes within 30 days of surgery were also analyzed.

This study included 366 patients, 133 in the D2 lymphadenectomy group and 233 in the D2 lymphadenectomy plus complete mesogastrium excision group. There was no statistically significant difference in 5-year disease-free survival and overall survival in the D2 lymphadenectomy plus complete mesogastrium excision group compared with the D2 lymphadenectomy group (P > .05). Regarding recurrence pattern, the D2 lymphadenectomy group had a higher rate of local recurrence (12.3% and 38.3%, P = .001). In subgroup analysis, patients with stage III and T3-4aN1-3 gastric cancer in the D2 lymphadenectomy plus complete mesogastrium excision group had significantly better 5-year disease-free survival compared with the D2 lymphadenectomy group (P < .05).

Laparoscopic D2 lymphadenectomy plus complete mesogastrium excision not only decreased the local recurrence rate of stage II/III gastric cancer without invasion of the squamocolumnar junction, but it also improved the 5-year disease-free survival of patients with stage III and T3-4aN1-3 gastric cancer without invasion of the squamocolumnar junction.

Conventional ypT category evaluates the depth of invasion after neoadjuvant therapy (NAT) for gastric cancer (GC) and has limited prognostic value. Tumor regression grade (TRG) measures the extent of tumor response to treatment, and when combined with the ypN category, it may enhance the prediction of patient outcomes. This study aims to develop a new staging system by integrating TRG and ypN category to better evaluate the prognosis of GC patients receiving NAT.

This retrospective analysis included 962 patients who underwent radical gastrectomy after NAT, with 513 in the development cohort (from one center) and 449 in the external validation cohort (from five centers). The ypN-TRG staging system was established by calculating the distance from the origin on a cartesian plane incorporating the ypN (x-axis) stage and TRG (y-axis) grade, and five sub-stages were delineated.

In the development cohort, 3-year overall survival rates according to ypN-TRG stage I, IIA, IIB, IIIA, IIB were 87.6%, 80.2%, 70.7%, 47.3%, 21.5%, p < 0.01. Compared with ypTNM, the ypN-TRG staging system performed better in terms of the prognostic discrimination power (C-index), goodness-of-fit (AIC, BIC), model improvement (NRI, IDI), and model stability (time-AUC). Multivariate Cox regression analysis confirmed the superiority of ypN-TRG over ypTNM staging. In the external validation cohort, ypN-TRG staging was a better predictor of OS and DFS in patients with GC.

The ypN-TRG staging system is superior to the AJCC eighth edition ypTNM staging system in accurately assessing the prognosis of patients with GC after NAT.

Few studies have focussed on using histological phenotype to evaluate prognostic factors after adjuvant chemotherapy (AC) in patients with pStage II/III gastric cancer. We evaluated the impact of histological type based on the World Health Organization classification.

Overall, 348 patients with pStage II/III advanced gastric cancer undergoing R0 gastrectomy without neoadjuvant chemotherapy were included. Of these, 143 underwent AC. Univariate and multivariate analyses for prognostic factors of relapse-free survival (RFS) and overall survival (OS) were performed in all patients and patients receiving AC. Moreover, long-term survivals were compared by histological phenotype between patients with and without AC.

Multivariate analysis in all patients revealed that histologically poorly cohesive carcinoma with not otherwise specified and signet ring cell subtype (PCC-NOS/SRC) and pN 2/3 independently and adversely affected RFS. Alternatively, male sex, poor PS and pN 2/3 adversely affected OS. In multivariate analysis of patients receiving AC, longer tumour size (≥ 80 mm), histologically PCC-NOS/SRC phenotype and pN 3 independently influenced RFS. Multivariate analysis in this population for OS revealed that pN 3 and poor postoperative immune-nutritional status significantly induced worse OS. Comparison of RFS and OS by histological phenotype between patients with and without AC showed that AC had no efficacy for improving long-term survivals in histologically PCC phenotype.

Histologically PCC phenotype by WHO classification, particularly PCC-NOS/SRC phenotypes, showed poor long-term RFS even after AC in patients with pStage II and III gastric cancer. An effective chemotherapeutic regimen needs to be developed for this specific subtype of gastric cancer.

To develop and validate a radiomics signature, utilizing baseline and restaging CT, for preoperatively predicting progression-free survival (PFS) after neoadjuvant chemotherapy (NAC) in locally advanced gastric cancer (LAGC).

A total of 316 patients with LAGC who received NAC followed by gastrectomy were retrospectively included in this single-center study; these patients were split into two cohorts, one for training (n = 243) and the other for validation (n = 73), based on the different districts of our hospital. A total of 1316 radiomics features were extracted from the volume of interest of the gastric-cancer lesion on venous phase CT images. Four radiomics signatures were built for predicting PFS based on baseline CT (Pre-Rad), restaging CT (Post-Rad), delta radiomics (Delta-Rad) and multi-time radiomics (PrePost-Rad), respectively. Then the PrePost-Rad was combined with clinical factors to establish a nomogram (Rad-clinical model). Kaplan-Meier survival curves with log-rank tests were used to assess the prognostic usefulness of the Rad-clinical model.

All baseline characteristics were not statistically different between the two cohorts. The PrePost-Rad achieved improved predictive value by a C-index of 0.724 (95% CI: 0.639-0.809) in the validation cohort [Pre-Rad: 0.715 (0.632-0.798); Post-Rad: 0.632 (0.538-0.725), Delta-Rad: 0.549 (0.447-0.651)]. In terms of clinical benefit, calibration capability, and prediction efficacy, the Rad-clinical model performed well for PFS prediction, with a C-index of 0.754 (95% CI: 0.707-0.800) and 0.719 (95% CI: 0.639-0.800) in the training and validation cohorts, respectively, superior to the clinical model (cN stage and CA199) but comparable to the PrePost-Rad. Moreover, the Rad-clinical model could accurately classify gastric-cancer patients after NAC into three PFS risk groups in both training and validation cohorts. The risk stratification also performed well in most subgroups (good responders, poor responders, ypTNM Ⅱ, and ypTNM Ⅲ/Ⅳ).

The Rad-clinical model integrating longitudinal radiomics score and clinical factors performed well in preoperatively predicting PFS of LAGC patients after NAC and surgery.

Gastric cancer remains a major health challenge worldwide, with nearly 1 million new cases annually contributing to more than 650 000 deaths. Epidemiologically, gastric cancer shows substantial geographical variation in incidence, with higher rates in Asia, South America, and eastern Europe, and a rapid increase in early-onset cases among people younger than 50 years. Key risk factors for gastric cancer include Helicobacter pylori infection, diet, obesity, smoking, and genetic predisposition. Early detection through comprehensive diagnostic procedures is crucial for optimising treatment outcomes. Standard treatment approaches for locally advanced gastric cancer include surgical resection, particularly D2 lymphadenectomy, complemented by chemotherapy and radiotherapy. There is increasing implementation of minimally invasive surgical techniques for operable disease and integration of immune checkpoint inhibitors and targeted therapies for advanced stages. Emerging therapies, such as novel targeted treatments and next-generation immunotherapies, show promise in improving survival and quality of life. Future directions in the management of gastric cancer focus on precision medicine, continued advancement in immunotherapy, novel early detection methods, and a multidisciplinary approach to care. These strategies aim to enhance the overall effectiveness of treatment and prognosis worldwide.

Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of cardiovascular and thromboembolic events. However, the incidence of cardiovascular and thromboembolic events associated with ICIs in gastroesophageal cancers is unknown.

We performed a propensity score-matched cohort study using the TriNetX Analytics Network database, which comprises de-identified data from over 130 participating healthcare institutions. Patients who received ICI and chemotherapy were compared with those who received only chemotherapy. The primary outcomes were cardiovascular events including pericarditis, myocarditis, heart failure, myocardial infarction, ischemic stroke, atrial fibrillation, conduction disorders as well as venous thromboembolism (VTE) within 1-year of ICI or chemotherapy. We matched the cohorts based on predetermined variables including demographics, metastatic disease, chemotherapy, underlying comorbidities, and the use of cardiovascular and lipid-lowering medications.

We identified 1,448 patients who received ICI and chemotherapy and 11,966 patients who received chemotherapy only. After matching, 1,425 patients remained in each cohort. The mean age was 63.1 ± 12.7 years in the ICI and chemotherapy cohort and 62.9 ± 12.1 years in the chemotherapy-only cohort. ICI was associated with a higher incidence of pericarditis (45.6 vs. 30.9 cases per 1000 patient-years; HR 1.51 [95% CI 1.03-2.22]) and VTE (102.5 vs. 75.1 cases per 1000 patient-years; HR 1.40 [95% CI 1.09-1.80]). The incidence of other cardiovascular outcomes were similar between the two cohorts.

In this cohort study, the use of ICI and chemotherapy was associated with an approximately 40-50% increased risk of pericarditis and VTE than patients on chemotherapy only.

To develop a nomogram based on clinical features and spectral quantitative parameters to preoperatively predict the Lauren classification for locally advanced gastric cancer (LAGC).

Patients diagnosed with LAGC by postoperative pathology who underwent abdominal triple-phase enhanced spectral computed tomography (CT) were prospectively enrolled in this study between June 2023 and December 2023. All the patients were categorized into intestinal- and diffuse-type groups according to the Lauren classification. Traditional characteristics, including demographic information, serum tumor markers, gastroscopic pathology, and image semantic features, were collected. Spectral quantitative parameters, including iodine concentration (IC), effective atomic number (Zeff), and slope of the energy spectrum curve from 40 keV to 70 keV (λ), were measured three times for each patient by two blinded radiologists in arterial/venous/delayed phases (AP/VP/DP). Differences in traditional features and spectral quantitative parameters between the two groups were compared using univariable analysis. Independent predictors of the Lauren classification of LAGC were screened using multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to assess the discriminating capability. Ultimately, the nomogram, including clinical features and spectral CT quantitative parameters, was developed.

Gender, nIC in AP (APnIC), and λ in DP (λd) were independent predictors for Lauren classification. The nomogram based on these indicators produced the best performance with an area under the curve of 0.841 (95% confidence interval: 0.749-0.932), specificity of 85.3%, accuracy of 76.4%, and sensitivity of 68.4%.

The nomogram based on clinical features and spectral CT quantitative parameters exhibits great potential in the preoperative and non-invasive assessment of Lauren classification for LAGC.

Question Can the proposed nomogram, integrating clinical features and spectral quantitative parameters, preoperatively predict the Lauren classification in locally advanced gastric cancer (LAGC)? Findings The nomogram, based on gender, arterial phase normalized iodine concentration, and slope of the energy spectrum curve in the delayed phase showed satisfactory predictive ability. Clinical relevance The established nomogram could contribute to guiding individualized treatment strategies and risk stratification in patients by predicting the Lauren classification for LAGC before surgery.

Peritoneal carcinomatosis (PC) is a common pattern of recurrence in gastric cancer patients and is associated with a poor prognosis. This study aimed to evaluate the predictive value of the albumin-fibrinogen ratio (AFR) for PC in patients with gastric cancer and to develop two preoperative prediction models.

A total of 745 gastric cancer patients were included in this study. Preoperative AFR, along with other serum markers and clinical tumor characteristics, was assessed. Univariate and multivariate logistic regression analyses were performed to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of the independent variables. Propensity score matching (PSM) was used to control for potential confounders, and one-way ANOVA was conducted to evaluate differences in distribution between groups. Two prediction models incorporating the independent predictive indicators were constructed and validated via receiver operating characteristic (ROC) curves.

Poorly differentiated type (OR 2.679; P = 0.001), nondiffuse morphological type (OR 2.123; P = 0.040), BMI < 23.550 kg/m2 (OR 4.635; P = 0.001), AFR < 11.275 (OR 2.895; P = 0.003) and CA199 ≥ 73.615 U/mL (OR 2.040; P = 0.037) were identified as independent risk factors for PC in patients with gastric cancer. After PSM, the AFR remained the only inflammatory marker that was independently associated with PC (P = 0.003). AFR demonstrated consistent robustness in predicting PC across multiple sample sets. Among all the independent risk factors, the AFR had the highest area under the curve (AUC) for ROC analysis (AUC 0.648; 95% CI 0.580-0.715). Two combination models incorporating the AFR demonstrated enhanced predictive ability: Combination Model 1 (AUC 0.759; 95% CI 0.699-0.820) and Combination Model 2 (AUC 0.801; 95% CI 0.744-0.859).

The preoperative AFR serves as a useful indicator for predicting PC. Two reliable prediction models based on the AFR have been developed.

 Gastric cancer (GC) diagnosis and care data in South Africa (SA) is sparse, and SA has a high GC mortality rate. Mapping the GC care pathway is needed to explore its efficacy in association with the SA GC burden and mortality.

 The study aims to map the GC care pathway in SA from diagnosis to management by healthcare professionals (HCPs) involved in the GC patient journey and explore barriers and facilitators to the effective flow of the GC care pathway.

 Interviews conducted with South African HCPs were the data source used in this article for analysis. General physicians (GP) were the first contact point with chain-referral sampling sourcing other clinicians.

 Interviews were conducted via Microsoft Teams (MS Teams) and Google Meet with qualitative analyses via MAXQDA.

 Themes identified were GC care pathway processes, public versus private healthcare system differences and care pathway challenges. Multidisciplinary team (MDT) care is practised for GC in SA, starting with the GP or nurse followed by gastroenterologist (GI), surgeon and pathologist. Thereafter, nurses, dieticians and palliative care specialists are involved. Healthcare sector differences are diagnosis time, GC staging, HCP and treatment access. Challenges include low GC index of suspicion by primary care clinicians (PCC) and Helicobacter pylori (H. pylori) detection.

 A MDT approach for optimal treatment and patient care may be the best method for prolonged life.Contribution: A South African national consensus for GC care via a MDT, emphasising early diagnosis to aid in a robust treatment plan for improved patient outcomes is warranted.

Trastuzumab deruxtecan (T-DXd) has been approved for the treatment of human epidermal growth factor receptor-2 (HER2)-positive gastric cancer and other indications in several countries and is considered moderately or highly emetogenic. The management of nausea and vomiting associated with T-DXd treatment has not been fully evaluated and the effectiveness of conventional prophylaxis remains unknown.

This open-label, randomized, multicenter, phase 2 study aimed to investigate the optimal antiemetic therapy for Japanese patients with gastric cancer undergoing T-DXd treatment. Patients were randomized to a doublet regimen group (dexamethasone and palonosetron) or triplet regimen group (aprepitant, dexamethasone, and palonosetron) at a ratio of one to one, stratified by sex, gastrectomy status, and study institution. Both antiemetic treatments were administered from day 1 before T-DXd administration, and emetic events and nausea were observed for 21 days. The primary endpoint was the antiemetic complete response (CR) rate to assess control for emetic events based on voluntary patient-reported outcomes (PROs) during cycle 1 (1-21 days).

Of the 60 enrolled patients, 58 were eligible for inclusion in this analysis (29 patients in each regimen group). The overall CR rates for the doublet and triplet regimens were 41.4% (12/29 patients) and 37.9% (11/29 patients), respectively, and neither regimen met the pre-specified threshold (> 18/29 patients). The CR rate in the acute phase (0-24 h) was 86.2% (25/29 patients) for both regimens, and the CR rates in the delayed phase (2-21 days) were 41.4% (12/29 patients) and 37.9% (11/29 patients) for the doublet and triplet regimens, respectively.

Given that the primary endpoint was not met, further research is needed to better characterize nausea and vomiting with T-DXd to tailor an anti-emetic regimen that suits the needs of the patients.

To establish and validate a model based on deep learning (DL), integrating radiomic features with relevant clinical features to generate nomogram, for predicting preoperative serosal invasion in gastric cancer (GC).

This retrospective study included 335 patients from dual centers. T staging (T1-3 or T4) was used to assess serosal invasion. Radiomic features were extracted from primary GC lesions in the venous phase CT, and DL features from 8 transfer learning models were combined to create the Hand-crafted Radiomics and Deep Learning Radiomics (HCR-DLR) model. The Clinical (CL) model was built using clinical features, and both were combined into the Clinical and Radiomics Combined (CRC) model. In total, 15 predictive models were developed using 5 machine learning algorithms. The best-performing models were visualized as nomograms.

The total of 14 radiomic features, 13 DL features, and 2 clinical features were considered valuable through dimensionality reduction and selection. Among the constructed models: CRC model (AUC, training cohort: 0.9212; internal test cohort: 0.8743; external test cohort: 0.8853) than HCR-DLR model (AUC, training cohort: 0.8607; internal test cohort: 0.8543; external test cohort: 0.8824) and CL model (AUC, training cohort: 0.7632; internal test cohort: 0.7219; external test cohort: 0.7294) showed better performance. A nomogram based on the logistic CL model was drawn to facilitate the usage and showed its excellent predictive performance.

The predictive performance of the CRC Model, which integrates clinical features, radiomic features, and DL features, exhibits robust predictive capability and can serve as a simple, non-invasive, and practical tool for predicting the serosal invasion status of GC.

To longitudinally evaluate pathologic response outcomes after neoadjuvant immuno-chemotherapy (NICT) for patients with locally advanced gastric cancer (LAGC) using pre- and post-treatment dual-energy CT (DECT).

Between Jan 2021 and Dec 2023, 115 patients who underwent NICT plus gastrectomy and triple-phase enhanced DECT scans before and after NICT were retrospectively enrolled. Pathologic tumor regression grade (TRG) was the reference standard, patients were labelled as responders (TRG = 0 + 1) and non-responders (TRG = 2 + 3) accordingly. A two-dimensional free-hand region of interest method was adopted to obtain the iodine concentration (IC) values. Pre- and post-NICT IC and normalized IC (nIC) were measured at arterial/venous/delay phase (AP/VP/DP), respectively; their changes [ΔIC (%)] defined as (IC_post-IC_pre)⁄IC_pre × 100% were calculated. Pre- and post-NICT imaging parameters and their changes were compared between different response groups. Non-responders' associated parameters were selected using multivariable logistic regression analysis. Their performances were analyzed by the area under the receiver operating characteristic curve (AUC). Their associations with patient survival were explored by using Kaplan-Meier survival analysis.

ICDP-pre, ΔICAP, thickness-post with cut-off value of > 2.306 mg/mL, ≤ 26.70%, > 18.5 mm, respectively, indicates non-responders with equivalent AUC being 0.616 (95% CI: 0.521-0.705), 0.625 (95% CI: 0.529-0.713), and 0.660 (95% CI: 0.565-0.745). Their combination demonstrated an improved AUC of 0.774 (95% CI: 0.686-0.846) and was associated with patient disease-free survival (DFS) with a hazard ratio being 2.239 (95% CI: 1.004-4.991) (p = 0.026).

Pre- and post-NICT DECT-based quantifications are useful for longitudinal assessment of pathologic response outcomes after NICT in LAGC. ICDP-pre, ΔICAP, and thickness-post are equally useful, their combination demonstrated incremental benefit.

Question Accurate evaluation of the efficacy of NICT in patients with LAGC remains challenging due to the lack of effective biomarkers. Findings Sequential DECT-based ICDP-pre, ΔICAP, and tumor thickness-post were predictive of TRG status. Their combination demonstrated enhanced performance and was associated with patient DFS. Clinical relevance DECT represents a promising imaging technique with added advantages for longitudinal assessment of pathologic response to NICT in LAGC, potentially facilitating more personalized treatment strategies among this population.

Highly expressed in the gastrointestinal mucosa, huntingtin-associated protein 1 (HAP1) is closely associated with tumor development and prognosis.

To investigate the clinical utility of HAP1 expression in gastric cancer (GC).

We randomly selected 124 GC patients had not undergone preoperative radiotherapy or chemotherapy, they were diagnosed at the Central Hospital of Wuhan between May 2013 and October 2018. Immunohistochemistry was used to detect HAP1 expression in paraffin-embedded GC tissues, as well as metastatic lymph nodes. Their clinical data were collected and all participants were follow up for 5 years. Western blotting and quantitative polymerase chain reaction were used to detect HAP1 levels in 20 matched pairs of fresh GC tissues.

HAP1 protein and mRNA levels were lower in fresh GC tissues than in normal mucosal tissues (P < 0.001, respectively). Immunohistochemistry also revealed lower HAP1 expression in GC tissues and metastatic lymph nodes than in normal mucosal tissues (P < 0.05). HAP1 expression in GC was closely associated with differentiation, lymph node metastasis, lymph node ratio, remote metastasis, clinical stage, tumor location, and survival time (P < 0.05). Furthermore, HAP1 expression independently predicted GC (P < 0.05) and was more accurate in advanced GC than in early GC (P < 0.05).

HAP1 is an important prognostic biomarker for GC, with low HAP1 expression positively correlating with poor overall survival, especially in advanced clinical stages.

Cancer is the leading cause of death worldwide characterized by patient heterogeneity and complex tumor microenvironment. While the genomics-based testing has transformed modern medicine, the challenge of diverse clinical outcomes highlights unmet needs for precision oncology. As functional molecules regulating cellular processes, proteins hold great promise as biomarkers and drug targets. Mass spectrometry (MS)-based clinical proteomics has illuminated the molecular features of cancers and facilitated discovery of biomarkers or therapeutic targets, paving the way for innovative strategies that enhance the precision of personalized treatment. In this article, we introduced the tools and current achievements of MS-based proteomics, choice of discovery and targeted MS from discovery to validation phases, profiling sensitivity from bulk samples to single-cell level and tissue to liquid biopsy specimens, current regulatory landscape of MS-based protein laboratory-developed tests (LDTs). The challenges, success and future perspectives in translating research MS assay into clinical applications are also discussed. With well-designed validation studies to demonstrate clinical benefits and meet the regulatory requirements for both analytical and clinical performance, the future of MS-based assays is promising with numerous opportunities to improve cancer diagnosis, treatment, and monitoring.