The role of sarcopenic obesity for the prediction of prognosis of patients with gastrointestinal cancer.

BACKGROUND: Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population. METHODS: We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival. RESULTS: Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm2/m2 with VFA ≥ 126.30 cm2 in men and SMI ≤32.05 cm2/m2 with VFA ≥72.42 cm2 in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions. CONCLUSIONS: Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients.

Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.

Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. We hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer. We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and in vivo. TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers in vitro including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. In vivo anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition. Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status in vivo. TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-Cell Lymphoma.

BACKGROUND Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common histological subtype of extra-nodal DLBCL, but the risk factors, prognostic biomarkers, histopathological classifications, and treatment strategies have not had significant progress. Emerging evidence shows that cystatin SN (CST1) is involved in tumor progression in several cancer types, but its role in GI-DLBCL has not been revealed. MATERIAL AND METHODS We established a cohort consisting of 84 patients with GI-DLBCL who underwent surgical resection. The expression of CST1 in the cohort was investigated by immunohistochemistry, which divided the patients into subgroups with low or high expression of CST1. Moreover, the CST1 expression in GI-DLBCL tissues or adjacent GI tissues were compared with RT-qPCR. The correlation between CST1 expression and clinicopathological factors was analyzed with the chi-square test. The prognostic significance of CST1 was estimated by univariate and multivariate analysis, and statistical significance was analyzed with the log-rank test. RESULTS CST1 was aberrantly upregulated in GI-DLBCL tissues compared with in non-tumor GI tissues. High expression of CST1 indicated poor prognosis of GI-DLBCL (P=0.012), and CST1 can be regarded as an independent prognostic biomarker of GI-DLBCL (hazard ratio=3.07). In our study, serum lactate dehydrogenase (P=0.002), performance status (P=0.003), Lugano stage (P=0.002), and International Prognostic Index (P=0.001) were also prognostic factors of GI-DLBCL. CONCLUSIONS CST1 is an independent prognostic biomarker of GI-DLBCL, indicating unfavorable prognosis. Our results suggested that CST1 detection can be a promising method to stratify high-risk patients and guide individual treatment.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

Pulmonary tumor thrombotic microangiopathy: Two case reports and literature review.

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.

[Gastrointestinal neuroendocrine tumors: update 2024]. / Gastrointestinale neuroendokrine Tumoren ­ Update 2024.

Gastrointestinal neuroendocrine tumours (NETs) are rare and clinically heterogeneous. From a diagnostic perspective, well-differentiated tumours must be distinguished from poorly differentiated neuroendocrine carcinomas. The disease may be associated with autonomous hormone secretion by the tumour, and the resulting syndromes are often associated with reduced survival. Somatostatin analogues form the backbone of antiproliferative and antisecretory treatment alongside local ablative procedures. In pancreatic NET, prospective studies confirm the value of specific chemotherapy, particularly in terms of higher remission rates. New tyrosine kinase inhibitors are an option for patients that have failed to respond to standard treatments. Inhibition of HIF2-alpha is an emerging effective treatment option for patients with von Hippel-Lindau-syndrome associated tumours, e.g. pancreatic NET. Radioligand therapy is an established second-line option for advanced NET of the small intestine, and recent study results support its use in pancreatic NET in earlier-line treatment. Due to the complexity of the disease, management of NET patients should be performed in close collaboration with a specialized multidisciplinary team.

Patient and Provider Attitudes and Preferences Regarding Early Palliative Care Delivery for Patients with Advanced Gastrointestinal Cancers: A Prospective Survey.

Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes between patients and their providers regarding the delivery of EIPC. Patients with newly diagnosed incurable gastrointestinal (GI) cancer at a tertiary cancer centre in Ontario, Canada, were surveyed using a study-specific instrument regarding the importance of and preferences for accessing support across eight domains of palliative care. Physicians within the circle of care completed a parallel survey for each patient. The concordance between patient and physician responses was analyzed. A total of 66 patients were surveyed (median age 69, 35% female). All had an oncologist, 12% had a specialist palliative care provider (SPC), and 97% had an FD, but only 41% listed the FD as part of the care team. In total, 95 providers responded (oncologist = 68, FD = 21, SPC = 6; response rate 92%; 1-3 physician responses per patient). Disease management and physical concerns were most important to patients. Patients preferred to access care in these domains from oncologists or SPCs. For all other domains, most patients attributed primary responsibility to self or family rather than any healthcare provider. Thus, concordance was poor between patient and physician responses. Across most domains of palliative care, we found low agreement between cancer patients and their physicians regarding responsibilities for care, with FDs appearing to have limited involvement at this stage.

How to Balance Prognostic Factors in Controlled Phase II Trials: Stratified Permuted Block Randomization or Minimization? An Analysis of Clinical Trials in Digestive Oncology.

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

Epigenetic regulation of major histocompatibility complexes in gastrointestinal malignancies and the potential for clinical interception.

BACKGROUND: Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes. MAIN BODY: By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions. CONCLUSION: The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.

Development of an ensemble CNN model with explainable AI for the classification of gastrointestinal cancer.

The implementation of AI assisted cancer detection systems in clinical environments has faced numerous hurdles, mainly because of the restricted explainability of their elemental mechanisms, even though such detection systems have proven to be highly effective. Medical practitioners are skeptical about adopting AI assisted diagnoses as due to the latter's inability to be transparent about decision making processes. In this respect, explainable artificial intelligence (XAI) has emerged to provide explanations for model predictions, thereby overcoming the computational black box problem associated with AI systems. In this particular research, the focal point has been the exploration of the Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME) approaches which enable model prediction explanations. This study used an ensemble model consisting of three convolutional neural networks(CNN): InceptionV3, InceptionResNetV2 and VGG16, which was based on averaging techniques and by combining their respective predictions. These models were trained on the Kvasir dataset, which consists of pathological findings related to gastrointestinal cancer. An accuracy of 96.89% and F1-scores of 96.877% were attained by our ensemble model. Following the training of the ensemble model, we employed SHAP and LIME to analyze images from the three classes, aiming to provide explanations regarding the deterministic features influencing the model's predictions. The results obtained from this analysis demonstrated a positive and encouraging advancement in the exploration of XAI approaches, specifically in the context of gastrointestinal cancer detection within the healthcare domain.

[Gastrointestinal mucosa-associated lymphoma]. / Mukosaassoziierte Lymphome des Gastrointestinaltrakts.

Mucosa-associated lymphomas of the gastrointestinal tract are a heterogeneous group differing in pathogenesis, localization and therapeutic options. For all of them, differentiated treatment requires an exact determination of lymphoma stage. For gastric MALT lymphoma, the pathogenetic role of Helicobacter pylori infection has become evident in the last 30 years. These insights were consequently implemented into clinical practice. Nowadays, Helicobacter pylori eradication is the treatment of choice for gastric MALT lymphoma, leading to complete remission of the lymphoma in the majority of cases. In the absence of success, radiotherapy is available in localized stages I/II E with excellent results. Immuno-chemotherapy is the domain for advanced stages III/IV E, and surgery plays no role any more. The rare intestinal and colorectal MALT lymphomas require an individualized therapeutic approach.

Pilot Study by Liquid Biopsy in Gastrointestinal Stromal Tumors: Analysis of PDGFRA D842V Mutation and Hypermethylation of SEPT9 Presence by Digital Droplet PCR.

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists' diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes.

Efficacy and adverse events of L-Asparaginase administration as a first-line treatment for feline large-cell gastrointestinal lymphoma.

L-Asparaginase (L-Asp) is often used to induce remission in feline large-cell gastrointestinal lymphoma (LCGIL). However, no study has evaluated the efficacy and adverse events following the initial use of this drug as a first-line treatment in feline LCGIL. We retrospectively reviewed medical records of cats with LCGIL treated with L-Asp to induce remission. This study included 43 cats. The response rate (RR) after the first administration of L-Asp was 37.2% (Complete remission: 7.0%, partial remission: 30.2%). RR was significantly higher in cases with primary gastric lesions (64.3%) than in those with primary intestinal lesions (24.1%) (P=0.018), and it was also higher in cases without anemia (57.1%) than those with anemia (15.0%) (P=0.009). The most common adverse event was hyperammonemia, which occurred in 10 of 12 cases where we could compare plasma ammonia concentrations before and after the first dose of L-Asp. Plasma phosphate concentrations were also significantly increased (P<0.001) within 24 hr after the first dose. Decreased appetite, vomiting, and diarrhea were also observed in five, three, and seven cases, respectively, and Grade 3 or higher gastrointestinal signs were observed as adverse events in three cases. The median overall survival of all cats was 150 days (range, 5-1,065 days), and the median progression-free survival was 104 days (range, 2-978 days). In conclusion, L-Asp was effective to induce remission, and severe adverse events were uncommon in feline LCGIL.

The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.

BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.

Combined exercise on fatigue, quality of life and physical functioning in people under chemotherapy with oxaliplatin: Systematic review and meta-analysis.

OBJECTIVE: To investigate the effects of combined exercise on fatigue, anxiety, depression, quality of life and physical functioning in gastroinstestinal neoplasm in people under chemotherapy with oxaliplatin treatment. METHODS: We searched pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (until Nov 2023) for randomized controlled trials that investigated the effects of combined exercise in gastroinstestinal neoplasm people under chemotherapy with oxaliplatin treatment. Two comparisons were made: combined exercise versus usual care, combined aerobic and versus usual care (follow up). The main outcomes were muscle strength, aerobic capacity, fatigue, anxiety, depression and quality of life. Mean differences (MD) with 95% confidence interval (CI) were calculated. RESULTS: Seven randomized controlled trials met the eligibility criteria, which included 464 people. Compared to usual care, combined aerobic and resistance resulted in decrease of general fatigue (-2.82; IC: 4.92 to -0.69, N = 48), physical fatigue (-5.08; IC: 8.41 to -1.74, N = 48) and improvement of domain physical functioning of quality of life (9.40; IC: 2.74 to 16.06, N = 48). Compared to usual care, combined aerobic and resistance - Follow up resulted in decrease of general fatigue (-2.32; IC: 4.41 to - 0.28, N = 48), physical fatigue (-0.92; IC: 3.31 to -1.47, N = 48) and improvement ofdomain physical functioning of (9.83; IC: 0.66 to 19.01, N = 48). CONCLUSIONS: Our results demonstrate that combined exercises improves fatigue (general; physical), domain physical functioning of quality of life in gastrointestinal neoplasm people under chemotherapy treatment when compared to usual care.

The Burden of Overweight and Obesity-Associated Gastrointestinal Cancers in Low and Lower-Middle-Income Countries: A Global Burden of Disease 2019 Analysis.

INTRODUCTION: Obesity is associated with cancer, including gastrointestinal (GI). Data from low (LICs) and lower-middle-income countries (MICs) are limited. METHODS: We utilized data from the Global Burden of Disease Study 2019 to determine the mortality from GI cancer risk of high body mass index (BMI) in these countries. RESULTS: Mortality rates of GI cancers from high BMI increased in LICs and lower MICs, while burdens decreased or remained stable in high and middle-income countries. DISCUSSION: The GI cancer-related burden from high BMI increased in LICs and lower MICs, necessitating a concerted effort to tackle the obesity pandemic.

Ultra-Processed Food Consumption and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ultra-processed food (UPF) intake has been associated with a higher risk of obesity, hypertension, type 2 diabetes, and cardiovascular diseases. The initial data on the relationship between UPF consumption and cancer risk were derived from retrospective observational studies with conflicting results. This systematic review and meta-analysis of prospective cohort studies aimed to investigate the association between UPF consumption and gastrointestinal cancer risk. METHODS: PubMed, Embase, and Cochrane databases were searched for prospective cohort studies that compared the highest vs the lowest level of UPF consumption according to NOVA food classification and reported the risk of gastrointestinal cancers by subsite. The association with cancer was quantified as hazard ratios (HR) using a random-effects model. RESULTS: Five prospective cohort studies were included in this review comprising 1,128,243 participants (241,201 participants in the highest and 223,366 in the lowest levels of UPF consumption). The mean follow-up ranged from 5.4 to 28 years. The highest UPF consumption was significantly associated with an increased risk of colorectal cancer (HR 1.11; 95% confidence interval [CI] 1.03-1.21; P = 0.01; I2 = 31%), colon cancer (HR 1.12; 95% CI 1.02-1.23; P = 0.02; I2 = 0%), and non-cardia gastric cancer (HR 1.43; 95% CI 1.02-2.00; P = 0.04; I2 = 0%) compared with the lowest UPF intake. However, no association was found between high UPF consumption and hepatocellular, esophageal, pancreatic, gastric cardia, and rectal cancer. DISCUSSION: The highest level of UPF consumption was significantly associated with colorectal and non-cardia gastric cancer.

The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.