Onset of depression among gastrointestinal cancer survivors: an All of Us Research Program study.

Reporting of baseline characteristics in gastrointestinal cancer: A systematic review of surgical randomised controlled trials.

mRNA vaccines in gastrointestinal cancers: Mechanistic basis, translational challenges, and emerging therapeutic strategies.

Cadherin-17 (CDH17) is a cell-adhesion molecule physiologically expressed along the intestinal epithelial tight junctions. Aberrant overexpression of CDH17 in gastrointestinal (GI) cancers promotes tumor growth and metastasis and is associated with poor patient prognosis. Due to its restricted expression in normal tissues and strong association with malignancy, CDH17 represents an emerging therapeutic target for GI tract cancers. A high-affinity anti-CDH17 monoclonal antibody (TAVO307) was generated and conjugated with auristatin-derived cytotoxic payloads to obtain CDH17-directed antibody-drug conjugates (ADCs). In parallel, a VHH antibody capable of activating γδ T cell receptors from both Vδ1 and Vδ2 subsets was identified and combined with the anti-CDH17 antibody to generate CDH17-targeted T cell engager (TCE) to recruit γδ T cells, which are abundant in the intestinal mucosa and play a critical role in tumor immunosurveillance. An attenuated interleukin-15 (IL-15) fused with the IL-15 receptor α sushi domain was further incorporated on TCE to enhance γδ T cell expansion and activation. CDH17-based ADCs exhibited potent and selective cytotoxicity in multiple GI cancer cell lines and significant tumor regression in xenograft models. The CDH17 γδ TCE induced tumor antigen-dependent γδ T cell degranulation and redirected both Vδ1 and Vδ2 T cells to effectively kill CDH17-expressing cancer cells. IL-15 fusion further augmented γδ T cell expansion and activation. Both CDH17-targeted ADCs and γδ TCEs demonstrated promising potency and efficacy to control GI cancers. They could offer complementary therapeutic options that could be used in combination therapy.

Metabolic interactions of host-gut microbiota: Shaping the future of precision diagnosis and therapeutic discovery in gastrointestinal cancers.

Fluoropyrimidine regimens in gastrointestinal oncology have evolved empirically. Bolus 5-fluorouracil (5-FU)-containing combinations now coexist with continuous metronomic schedules and oral prodrugs, while immune checkpoint inhibitors (ICIs) seek chemotherapy partners for microsatellite-stable (MSS) gastrointestinal cancers. This review examines the intersection of bolus omission, metronomic scheduling, and biomarker-selected immunochemotherapy and proposes a shift from dose-based to exposure-based paradigms. A real-world cohort of 11 765 patients showed that bolus omission from FOLFOX, FOLFIRI and FOLFIRINOX preserved survival and approximately halved grade 3-4 haematological toxicity. CAIRO3 validated low-dose continuous capecitabine maintenance, pharmacologically consistent with metronomic dosing. Preclinical murine studies suggest that fluoropyrimidine immune effects are dose-, schedule- and partner-dependent, with peak exposure activating NLRP3-driven pro-tumour pathways; relevance to human disease remains hypothetical. Two recent signals (POCHI and MEDITREME) share early-line treatment, immune or molecular enrichment, and an oxaliplatin-driven immunogenic cell death inducer; POCHI also avoids intravenous 5-FU bolus through its CAPOX backbone. Recent failures of chemo-immunotherapy in MSS gastrointestinal cancers may partly reflect immunologically suboptimal chemotherapy backbones. Optimal outcomes likely require joint consideration of schedule, biomarker selection, and immunogenic partner. Prospective trials testing chemotherapy schedules are warranted.

Gastrointestinal cancer (GIC) frequently causes cancer cachexia, the major feature of which is the loss of skeletal muscle mass. The degradation of muscular proteins by cancer‑derived factors in the major pathogenesis of cancer‑induced muscle wasting is a known phenomenon. However, this mechanism has mainly been demonstrated using rodent cancer cells, and it may not always be applicable to human cancer types. Impaired skeletal muscle differentiation and regeneration have attracted attention as alternative inducers of cancer cachexia. The present study revealed that conditioned medium from four human GIC cell lines inhibited C2C12 myoblast differentiation by inducing the expression of the inhibitor of DNA binding (Id) proteins Id1 and Id3, which mediated via bone morphogenetic protein (BMP)‑Smad signaling. The results suggested that BMP‑Smad1/5/8‑Id signaling inhibited the expression of a MRF member, myogenin and its downstream myogenic genes, thus leading to unsuccessful differentiation into myotubes. Furthermore, the present study identified high levels of BMP4 secretion from these four human GIC cell lines and demonstrated that an inhibitor of BMP receptor, dorsomorphin or abrogation of BMP4 by siRNA in the GIC cells restored myogenic differentiation in C2C12 cells. The present study uncovered, for the first time, that BMP4 derived from human GIC cells exogenously inhibited myoblast differentiation by activating the Smad1/5/8‑Id signaling axis. In the future, this in vitro study may help to elucidate the complicated mechanisms underlying cancer‑induced cachexia in humans.

Longitudinal trajectories of treatment-course-associated biological aging predict treatment tolerance and survival after gastrointestinal cancer surgery.

Dihydropyrimidine dehydrogenase phenotype-guided dose individualization of fluoropyrimidine in gastrointestinal cancers: PRODIGE100-UCGI48-FUDOSE phase II study.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes and is associated with poor prognosis. Long considered an undruggable target, KRAS has recently become actionable with the development of direct inhibitors, particularly against the G12C mutation. Our group previously reported promising efficacy and safety results for glecirasib (JAB-21822), a novel KRASG12C inhibitor, in phase I/II trials involving solid tumors harboring KRASG12C mutations (ClinicalTrials.gov NCT05009329, NCT05194995). Nevertheless, primary (5.61%) and acquired (9.64%) resistance were observed. This study analyzed 18 patients with advanced solid tumors harboring the KRASG12C mutation from the JAB-21822 cohort. Longitudinal blood samples (N = 45) were collected at baseline, during partial response or stable disease, and at disease progression. Circulating tumor cells (CTCs) were isolated via a microfluidics platform (CTC100, Cellomics) and categorized into epithelial (E-CTCs), mesenchymal (M-CTCs), and epithelial/mesenchymal mixed (E/M-CTCs) subtypes. At progression, the proportion of E-CTCs showed a decreased trend, while that of E/M-CTCs increased significantly (p = 0.03). In long-term responders, the inflection points of declining M-CTC levels correlated with clinical progression and were consistent with radiographic outcomes. Baseline CTC counts > 1 were associated with shorter progression-free survival (PFS; p = 0.046). E-CTC ≤ 1 correlated with longer PFS (p = 0.025), and M-CTC ≤ 1 with longer overall survival (OS; p = 0.033). E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05).

Minimally Invasive Surgery/Robotic Surgery in Small Bowel Cancer.

This study evaluated multimodal perioperative prehabilitation-combining exercise, nutrition, and psychological interventions-on functional capacity (6MWT distance, reflecting cardiopulmonary fitness) and clinical outcomes (postoperative complications, hospital stay, mortality, and readmission rates) in gastrointestinal cancer surgery. We conducted a systematic review and meta-analysis of 12 prospective trials (n=1229) identified via the PubMed, Web of Science, Cochrane Library, and Embase databases from their inception to March 20, 2025. Heterogeneity was evaluated with I2 and Q tests; random- or fixed-effects models were applied. Multimodal prehabilitation significantly improved the 6MWT preoperatively [mean difference (MD): 30.1m; 95% CI: 14.8-45.4] and at 4 weeks (MD: 21.5m; 95% CI: 14.1-28.9) and 8 weeks postoperatively (MD: 38.7m; 95% CI: 1.9-75.4). It was associated with a 0.86-day (95% CI: -1.43 to -0.30) shorter hospital stay and lowered overall [risk ratio (RR) 0.67; 95% CI: 0.57-0.79] and severe complications (RR: 0.77; 95% CI: 0.61-0.97), with no effect on operative time, mortality, or readmission. This study shows that patients receiving multimodal prehabilitation achieve better functional recovery (6MWT) and fewer complications, supporting its integration into perioperative care.

SPI1 mediates CST2 transcription to promote the proliferation, metastasis, and angiogenesis of esophageal cancer.

Patients with gastrointestinal cancer (GIC) often experience prevalent and severe malnutrition. Nutrition impact symptoms (NIS) can cause malnutrition but have not been fully addressed in GIC. This study comprehensively evaluated the prevalence and prognostic value of NIS in GIC. Baseline and laboratory characteristics of 6,732 patients with GIC were obtained from the INSCOC study. NIS includes inappetence, dysphagia, pain, nausea, early satiety, astriction, vomiting, xerostomia, diarrhea, dysgeusia, dysosmia, and mouth ulcer. The association between NIS and overall survival (OS) was determined using Cox regression analysis. NIS that showed independent prognostic values were included in subsequent analyses and defined as GIC-prognosis-related NIS (GICPNIS). GICPNIS score and weighted GICPNIS score were formulated based on the number and weight of GICPNIS, respectively. Of 6,732 patients, 2,877 patients had NIS. Multivariate analysis showed that inappetence [hazard ratio (HR)=1.20, 95% confidence interval (CI)=1.09-1.32], nausea (HR=1.31, 95%CI=1.16-1.47), vomiting (HR=1.40, 95%CI=1.22-1.60), dysphagia (HR=1.47, 95%CI=1.31-1.64), early satiety (HR=1.35, 95%CI=1.18-1.54), and pain (HR=1.53, 95%CI=1.29-1.81) were independent prognostic factors of patients with GIC (all p<0.001). Weighted GICPNIS score could better discriminate OS than GICPNIS score. Among patients with GIC, 42.7% experienced various NIS. Inappetence, nausea, vomiting, dysphagia, early satiety, and pain were independent prognostic factors of patients with GIC. Weighted GICPNIS score could better discriminate OS than GICPNIS score.

Epidemiological studies have revealed an inverse association between Alzheimer's disease and cancer. Here, we discuss the mechanisms involved in the relationship between Alzheimer's disease and gastrointestinal cancers, particularly pancreatic and gastric-colorectal cancers. The gut‒brain axis and pancreas‒brain axis connect the central nervous system with peripheral organs and form immune‒metabolic networks. We focus on bidirectional tumor-brain communication, involving cell-death pathways, apoptosis, metabolic dysregulation, microbiota, metabolic dysregulation, neuroinflammation, immune system and sensory-sympathetic circuits, and neural remodeling. Furthermore, we discuss potential integrated, multitarget therapeutic strategies, including metabolic regulation, microbiome interventions, and immune modulation. Prospective longitudinal cohorts incorporating prediagnostic exposures and molecular pathology are needed to establish temporality.

Perioperative morbidity in gastrointestinal (GI) cancers is closely associated with reduced physical fitness and impaired nutritional status. While prehabilitation has been shown to improve outcomes in patients with colorectal cancer (CRC), it is not yet standard of care and remains underexplored in other GI malignancies. This study evaluates the feasibility, safety, and preliminary effectiveness of a supervised moderate-to-high intensity exercise program combined with nutritional counseling in a cohort of GI cancer patients scheduled for surgery. In a prospective, two-arm, controlled trial, patients scheduled for GI cancer surgery were assigned to a prehabilitation program (2-3 sessions/week ≥ 3weeks, endurance and resistance training with nutritional counseling) or usual care. Primary endpoints were feasibility (eligibility, recruitment, acceptance, retention, adherence) and safety (adverse events). Secondary endpoint was quality of life (QoL; EORTC QLQ-C30 global score, SF-36 physical and mental health component scores, PCS, MCS), assessed at baseline (t0), presurgery (t1), hospital discharge (t2), and 12-week follow-up (t3). Among the 400 patients assessed for eligibility, 36% met the eligibility criteria. Of those approached, 41% consented to participate, resulting in an overall recruitment rate of 27% (n = 38). Of the recruited patients, 84% completed the study (n = 32; prehabilitation = 17; usual care = 15; mean age 63.5years, range 38-85; ICD-10 C15-C26). Participants attended 95% of the planned sessions (8.1 ± 3.6) within a mean of 30days (SD ± 16) and completed 59% at the target intensity. Nutritional counseling was provided to 94% of the patients. No intervention-related serious adverse events occurred. A modest improvement in PCS was observed in the prehabilitation group at t1 (+ 4.25 points), although this finding reached statistical significance only in the one-tailed analysis. No between-group differences were observed for global QoL or MCS. Multimodal prehabilitation combining supervised moderate-to-high intensity exercise with nutritional counseling is feasible and safe in a real-world GI cancer population. Recruitment and achievement of prescribed training intensity remain key challenges. Preliminary findings indicate short-term benefits for physical health, supporting further investigations in larger randomized trials. DRKS00028728; prospectively registered 05/05/2022.

Gastrointestinal cancers remain among the leading causes of cancer-related mortality worldwide. Beyond environmental and hereditary determinants, increasing evidence suggests that the gut microbiota may contribute to carcinogenesis through persistent infection, expression of virulence factors, and production of genotoxic metabolites. In this context, Helicobacter pylori has been firmly implicated in gastric carcinogenesis, while colibactin-producing Escherichia coli has emerged as a potential contributor to colorectal cancer development. The aim of this study was to explore the presence of colibactin-associated E. coli and virulence factor-harboring H. pylori strains in gastrointestinal cancer patients from a Turkish cohort. Tumor samples were collected from 19 patients with colorectal cancer and 4 patients with gastric cancer. In colorectal cancer samples, the presence of colibactin was assessed by screening for key genes (clbA, clbB, clbN, and clbQ). In gastric cancer samples, major H. pylori virulence determinants, including ureA, cagA, and vacA, were evaluated. Colibactin-associated genes were detected in approximately 21% of colorectal cancer patients (4/19), whereas 75% of gastric cancer cases (3/4) were positive for H. pylori virulence factors. Whole-genome sequencing (WGS) of two colibactin-positive isolates identified them as Escherichia coli Nissle and Citrobacter braakii. Given the limited sample size and exploratory design, these results are descriptive and intended to provide preliminary insight rather than establish causality. In conclusion, this study provides early evidence supporting the potential presence of genotoxin-associated bacteria and virulent H. pylori strains in gastrointestinal cancer patients in Türkiye. These findings underscore the need for larger, well-powered, and multi-omics-integrated studies to further elucidate the role of host-microbe interactions in gastrointestinal carcinogenesis.

Serum metabolic analysis based on label-free SERS fingerprints represents a highly promising technique for the detection of tumors. However, the insufficient hotspot density of SERS substrates often results in incomplete molecular Raman bands, hindering the accurate discrimination of tumors. Herein, we propose a clean, hydrophobic monolayer gold nanofilm/potassium iodide-encapsulated silver-coupled (Ag@KI/HMGF) SERS substrate. This triple-coupled SERS substrate achieves exceptional signal amplification and enables the acquisition of abundant SERS bands for multicomponent systems. Robust machine learning classifiers were employed to identify and analyze the Raman spectral features of serum metabolites, and this method exhibited high clinical accuracy, sensitivity, and specificity in distinguishing samples from patients with different types of gastrointestinal malignancies and healthy individuals. The serum metabolic analysis based on the coupled SERS substrate constructed in this study provides a highly promising solution to address the clinical challenge of gastrointestinal malignant tumor discrimination and can be further extended to clinical cancer detection based on other biological fluids.

Esophagectomy is associated with a higher incidence of venous thromboembolism, including pulmonary embolism (PE), than other gastrointestinal cancer surgeries. However, the true incidence of asymptomatic PE remains unclear. This study aimed to determine the incidence and associated factors of PE using routine contrast-enhanced computed tomography (CECT) after minimally invasive esophagectomy (MIE). A total of 134 consecutive patients who underwent MIE between May 2022 and December 2023 under a standardized postoperative CECT protocol were retrospectively analyzed. Routine CECT was performed on or after postoperative day (POD) 5 in all patients. Prophylactic anticoagulation was initiated based on bleeding risk. Study endpoints included PE incidence, identification of factors associated with PE, and the discriminative performance of postoperative coagulation and fibrinolysis biomarkers. PE developed in 13 patients (9.7%), and all cases were asymptomatic. Multivariable analysis identified BMI ≥ 22kg/m² as independently associated with PE (adjusted OR, 4.53; 95% CI, 1.27-21.4; P = 0.019). Sensitivity analyses showed consistent associations across adjusted models. Among postoperative biomarkers, D-dimer on POD 5 showed the highest discriminative performance for PE, whereas soluble fibrin monomer complex (SFMC) on POD 1 showed moderate discrimination. Despite prophylactic anticoagulation, asymptomatic PE occurred in 9.7% of patients after MIE. BMI ≥ 22kg/m² was independently associated with PE. Postoperative coagulation and fibrinolysis biomarkers, including POD 5 D-dimer and POD 1 SFMC, demonstrated discriminative performance and may provide complementary information in postoperative evaluation of PE.

The role of second surgical opinions (SSOs) in gastrointestinal (GI) cancer care is not well-defined. While SSOs are common, the impact may depend on whether patients ultimately undergo resection with the same surgeon or with a different surgeon after the SSO. We sought to characterize perioperative outcomes relative to SSO among older adults with GI cancers. Using SEER-Medicare data (2000-2019), patients aged 66-90 with primary GI were identified. Cancer-directed resections were categorized into three claims-observed pathways: surgery without SSO, SSO with same-surgeon resection, and SSO with different-surgeon resection. Multivariable regression models assessed the association between operative pathway and perioperative outcomes including complications, extended length of stay (LOS), 90-day readmission and mortality, discharge disposition, and achievement of a composite "textbook outcome." Among 40,603 surgical patients, 56.2% underwent surgery without SSO, 5.3% underwent SSO with same-surgeon resection, and 38.5% underwent SSO with different-surgeon resection. Compared with no SSO, SSO followed by resection with a different surgeon was associated with lower odds of 90-day readmission (aOR 0.92, 95%CI 0.88-0.97), any complications (aOR 0.90, 95%CI 0.84-0.95), extended LOS (aOR 0.93, 95%CI 0.88-0.98), and mortality (aOR 0.67, 95%CI 0.58-0.78), as well as higher discharge-home (aOR 1.05, 95%CI 1.01-1.12) and textbook outcome (aOR 1.12, 95%CI 1.07-1.17). In contrast, SSO with same-surgeon resection was associated with higher complications (aOR 1.14, 95%CI 1.01-1.29), longer LOS (aOR 1.21, 95%CI1.09-1.35), and lower home discharge (aOR 0.77, 95%CI 0.70-0.85) with no survival advantage. Among older adults undergoing GI cancer surgery, SSO followed by resection with a different surgeon was associated with improved perioperative safety and recovery, whereas SSO followed by resection with the same surgeon was not associated with similar benefit. These findings suggest that the value of SSO may lie in its role as a pathway to a different surgical team when clinically appropriate.