Types Of Gastrointestinal Cancers Research Articles

Pancreatic Cancer: A Review of Risk Factors

Pancreatic adenocarcinoma is one of the most lethal types of gastrointestinal cancer despite the latest medical advances. Its incidence has continuously increased in recent years in developed countries. The location of the pancreas can result in the initial symptoms of neoplasia being overlooked, which can lead to a delayed diagnosis and a subsequent reduction in the spectrum of available therapeutic options. The role of modifiable risk factors in pancreatic cancer has been extensively studied in recent years, with smoking and alcohol consumption identified as key contributors. However, the few screening programs that have been developed focus exclusively on genetic factors, without considering the potential impact of modifiable factors on disease occurrence. Thus, fully understanding and detecting the risk factors for pancreatic cancer represents an important step in the prevention and early diagnosis of this type of neoplasia. This review reports the available evidence on different risk factors and identifies the areas that could benefit the most from additional studies.

Using Social Media to Understand Primary Discussions in Gastrointestinal Cancers: Machine Learning Approach.

The incidence and mortality rates of gastrointestinal (GI) cancers are high in the United States as well as worldwide. The widespread use of social media provides unique opportunities to facilitate the dissemination of information, especially in the context of health. We aim to characterize the public's primary discussions, including perceptions, concerns, and interests toward GI cancers, from prevention, diagnosis, and treatment to survivorship care through the social media platform Twitter, using tweets posted by Twitter users. We analyzed 87 860 Twitter posts related to GI cancers. We used machine learning with natural language processing to identify salient topics and themes in the collected tweets. The most common themes across all GI cancer types included cancer risk prevention and awareness outreach programs, risk factors including lifestyles (primarily diet), and cancer survivorship-related discussions (primarily GI symptoms and quality of life). GI symptom-related tweets were prevalent in patients with colorectal and stomach cancers, whereas themes of newer clinical trials, end-of-life trials, palliative care trials, and disease prognosis were common in tweets related to liver/biliary and pancreatic cancers. Our research emphasizes the importance of individualized approaches in managing GI cancers, considering lifestyle and diet, the need for comprehensive survivorship care, raising awareness, delivering information, and improving targeted interventions related to GI cancers. Our study suggests utilizing Twitter data to better understand the real-world interest and concerns about GI cancers among the public, which can guide future patient-centered research in this field.

Il-6 and MSH3 in colorectal carcinoma: Expression, relationship, and prognostic significance in 171 colorectal carcinoma cases.

Colorectal cancer (CRC), the most common type of gastrointestinal cancer, mostly develops as a result of environmental factors. Inflammation is a relatively uncommon but crucial contributor to its etiology, and inflammation is also thought to pose a risk in patients without a clinical diagnosis of inflammatory bowel disease. In cell lines, the proinflammatory cytokine interleukin-6 (IL-6) causes a cytosolic shift in the mismatch repair protein MSH3, accompanied by functional loss. This study aimed to evaluate IL-6 and MSH3 expression in 171 sporadic CRC samples by immunohistochemistry (IHC). High levels of IL-6 are hypothesized to cause MSH3 expression loss. We also explored the clinical/pathological aspects of IHC-detected MSH3 loss and the relationship between MSH3 expression and tumor-infiltrating lymphocytes (TILs). IL-6 and MSH3 IHC and H and E slides were evaluated by two pathologists. Clinical data were obtained from the institution's database. A relationship between MSH3 loss and IL-6 expression was not proven (P = 0.963). MSH3 staining was significantly reduced in the patient group with high TILs (P = 0.035). We observed 104 CRC cases (60.8%) with IL-6 expression and 85 cases (49.7%) with reduced MSH3 expression. This study did not demonstrate an association between IL-6 and MSH3 expression. As MSH3 is a relatively little-known protein, further large-scale studies are needed. The use of IHC to identify patients who may benefit from anti-IL-6 therapies in CRC in the future may be critical.

Friend or Foe: Exploring the Relationship between the Gut Microbiota and the Pathogenesis and Treatment of Digestive Cancers.

Digestive cancers are among the leading causes of cancer death in the world. However, the mechanisms of cancer development and progression are not fully understood. Accumulating evidence in recent years pointing to the bidirectional interactions between gut dysbiosis and the development of a specific type of gastrointestinal cancer is shedding light on the importance of this "unseen organ"-the microbiota. This review focuses on the local role of the gut microbiota imbalance in different digestive tract organs and annexes related to the carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or by dietary changes, plays an important role in the future therapies of various digestive cancers.

The Role of Phytonutrient Kaempferol in the Prevention of Gastrointestinal Cancers: Recent Trends and Future Perspectives.

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.

Malnutrition and Related Factors in Older Patients With Gastrointestinal Cancer Receiving Chemotherapy.

Objectives The incidence and mortality of gastrointestinal (GI) malignancies increase exponentially with age. Malnutrition is a documented poor prognostic factor in older patients with cancer. There is insufficient data about the prevalence of malnutrition and associated factors in older patients with GI cancer. Thus, we aimed to investigate the prevalence of malnutrition and related factors among older patients with GI cancer. Methods A total of 121 patients aged over 70 years diagnosed with various types of GI cancers applied to the medical oncology clinic included in this cross-sectional study. We evaluated the nutrition status with a mini-nutritional assessment (MNA) score. Results The prevalence of malnutrition was 76 (62.8%) in our study population. The mean age was 76.5 (range 70 to 90 years), and 71 (58.6%) were male. In the multivariate logistic regression model, lower BMI (OR: 3.379, 95% CI: 1.465-7.812,p= 0.005), having gastroesophageal cancer (OR: 5.797, 95% CI: 2.387-14.091,p<0.001), treating with palliative chemotherapy (OR: 4.597, 95% CI: 1.799-11.772,p= 0.002), and frailty according to G8 score (OR: 10.798, 95% CI: 4.495-25.924,p<0.001) were associated with malnutrition. Conclusions Our study revealed that palliative chemotherapy, low BMI, frailty, and gastroesophageal cancer are risk factors for malnutrition in older patients with GI cancer. Physicians need to be aware of patients who may be at risk for malnutrition. Patients at risk of malnutrition may benefit from interventions to enhance their nutrition. Further studies consisting of larger cohorts are needed to determine malnutrition and related factors in older patients with cancer.

G-Protein Signaling Modulator 2 as a Potential Biomarker in Colorectal Cancer: Integrative Analysis Using Genetic Profiling and Pan-Cancer Studies.

Colorectal cancer (CRC) imposes a significant healthcare burden globally, prompting the quest for innovative biomarkers to enhance diagnostic and therapeutic strategies. This study investigates the G-protein signaling modulator (GPSM) family across several cancers and presents a comprehensive pan-cancer analysis of the GPSM2 gene across several gastrointestinal (GI) cancers. Leveraging bioinformatics methodologies, we investigated GPSM2 expression patterns, protein interactions, functional enrichments, prognostic implications, genetic alterations, and immune infiltration associations. Furthermore, the expression of the GPSM2 gene was analyzed using real-time analysis. Our findings reveal a consistent upregulation of GPSM2 expression in all GI cancer datasets analyzed, suggesting its potential as a universal biomarker in GI cancers. Functional enrichment analysis underscores the involvement of GPSM2 in vital pathways, indicating its role in tumor progression. The prognostic assessment indicates that elevated GPSM2 expression correlates with adverse overall and disease-free survival outcomes across multiple GI cancer types. Genetic alteration analysis highlights the prevalence of mutations, particularly missense mutations, in GPSM2. Furthermore, significant correlations between GPSM2 expression and immune cell infiltration are observed, suggesting its involvement in tumor immune evasion mechanisms. Collectively, our study underscores the multifaceted role of GPSM2 in GI cancers, particularly in CRC, emphasizing its potential as a promising biomarker for prognosis and therapeutic targeting. Further functional investigations are warranted to elucidate its clinical utility and therapeutic implications in CRC management.

Abstract 305: Bioinspired synthetic hydrogel in pancreatic cancer organoid matrix modeling

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality with a primary hallmark, including dense collagen matrix in the desmoplastic stroma. Organoid technologies often rely on commercially available EHS mouse sarcoma matrix materials, and it remains uncertain how batch-to-batch variability of this matrix impacts the consistency of cancer signaling. Here, we present a novel photo-activated hydrogel tuned to the properties of the desmoplastic stroma in PDAC organoid cultures. Method: We designed multiple synthetic hydrogel materials with tunable mechanical properties, including SP-139 (Stem Pharm, Inc), a polyethylene glycol-based hydrogel functionalized with norbornene and formed with both degradable and non-degradable crosslinking peptides and a cell adhesion peptide (CRGDS). We used rheometry to measure the elastic modulus of the polymerized hydrogel after visible light photoactivation (395 nm) and expanded multiple cancer organoid cultures. RNAseq was performed from patient-derived xenografts to expanded organoids across matrix designs (Cultrex® v. SP-139) and analyzed by GSVA pathway analyses. Result: We optimized the ratio of non-degradable v. degradable crosslinking peptide to support culture expansion and enzymatic digestion with dispase II (125 µg/mL) and collagenase II (1 mg/mL). Using rheometry, SP-139 at 75% v/v had increased elastic modulus versus Cultrex RGF BME matrix Type 2 at 100% v/v (4992±76.3 v. 68.4±5.6 Pa, p&amp;lt;0.0001). Phenotypic growth was confirmed across serial passages (&amp;gt;8) and a diversity of gastrointestinal cancer types (n=5). Baseline growth rates were identical over 48h between SP-139 (75% v/v) and Cultrex (50% v/v) (+13.4% v. +13.0, p=0.75). Growth remained consistent for SP-139 yet increased with Cultrex at interval of 48-96h (+12.9% SP-139 v +22.4% Cultrex, p&amp;lt;0.005) and interval of 96-144h (+13.6% SP-139 v +24.0% Cultrex®, p&amp;lt;0.0001). Therapeutic response was assessed using 3D CellTiter-Glo® using gemcitabine 100 µM (24h) with comparable inhibition of normalized cell viability in SP-139 v. Cultrex® (35.4±1.9% v. 52.3±6.5%, n.s.) and qualitatively with viability staining using calcein AM and Caspase 3/7FITC. RNAseq revealed Cultrex, when compared to SP-139, yielded down regulation of epoxygenase p450 pathways (padj&amp;lt;0.012) and negative regulation of the p38 MAP kinase cascade (padj&amp;lt;0.048). Conclusions: Functionalized PEG-based synthetic hydrogel matrix materials can be tuned for physical properties to mimic cancer tissue microenvironments more accurately. SP-139, designed to mimic the desmoplastic stroma of the pancreatic cancer microenvironment, has favorable properties including controlled growth rates and compatibility with high content imaging by luminescence and fluorescence. RNAseq pathway analysis shows SP-139 maintains pathways of p450 and MAP kinase signaling of importance with therapeutic resistance. Citation Format: Md Shahadat Hossan, Austin Stram, Ethan Samuel Lin, Sean McIlwain, Connie Lebakken, William Richards, Jeremy D. Kratz. Bioinspired synthetic hydrogel in pancreatic cancer organoid matrix modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 305.

Association of glucose-lowering drug target and risk of gastrointestinal cancer: a mendelian randomization study

Background & AimsGlucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study.MethodsTwo-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings.ResultsABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824–59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013–1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884–0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020–0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743–34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217–51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071–0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476–18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes.ConclusionsSome glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.

Comparing Endoscopy and Surgery: A Systematic Review of Early Colorectal Cancer Treatments

Colorectal cancer is a major type of gastrointestinal cancer that significantly contributes to disease burden and mortality, particularly among younger people. Early colorectal cancer refers to the early stages of the disease that require early detection and treatment to improve the overall prognosis and survival. There are various treatment options available for early colorectal cancer, such as endoscopic resection, including methods like transanal endoscopic microsurgery (TEMS), endoscopic mucosal resection (EMR), or submucosal dissection (ESD), as well as surgical resection, including open and laparoscopic techniques. However, to make informed decisions about which approach is best, it is crucial to thoroughly understand the long-term outcomes associated with each option. We systematically reviewed the PubMed and Google Scholar databases from 2013 to August 11, 2023, to obtain such knowledge. We selected nine for in-depth analysis after carefully reviewing 2761 articles, including those written in English and focusing on human studies. The review focused on individual benefits, merits, and drawbacks, considering the extent of the disease, clinical outcomes, survival, and complication rates. Although endoscopic resection has the advantage of being less invasive and promoting faster patient recovery, it should be noted that its primary objective may not necessarily be achieving complete excision (R0). This is because there are potential obstacles, including inadequate lymph node removal and inaccurate T staging that may prevent the achievement of R0. Nevertheless, it is important to stress that both endoscopic and surgical resection ultimately share the goal of complete excision and curing the patient. Finally, this systematic review emphasizes the need for additional research to fill knowledge gaps, improve clinical decision-making, and promote the application of sophisticated technology. As the landscape of early colorectal cancer treatment evolves, a balanced integration of endoscopic and surgical resection procedures, together with emerging technologies, can improve patient outcomes and increase treatment efficacy.

Abstract B011: Lower incidence of small intestinal adenocarcinomas may be due to constrained copy number karyotype and increased immune surveillance

Abstract Aim: To evaluate the genomic profiles of duodenal adenocarcinomas and explore the role of the immune system in the evolution of these cancers. Introduction: Tumours of the small intestine are rare and represent the smallest fraction of all gastrointestinal (GI) cancers despite being the largest organ in the GI tract. As a result, they have not been well characterised at the molecular level, and consequently are often clinically managed similarly to colorectal cancers. Methods: Here we performed shallow whole-genome sequencing (sWGS) on 125 cases of the most common adenocarcinomas in the small intestine, duodenal adenocarcinomas, and compared their somatic copy number aberrations to 880 upper and lower GI primary adenocarcinomas from the TCGA. Furthermore, we reanalysed published whole exome sequencing (WEX) from a further 91 small intestinal carcinomas to assess the immune landscape. Results: In our sWGS cohort, we found that duodenal adenocarcinomas have a significantly lower incidence of genome doubling (20%) than elsewhere in the GI tract (colon=43.6%, stomach=44%, rectum=55%, oesophagus=64.3%). Percentage of genome altered (PGA) is affected by the amount of genome doubling present, by median centering the proportion of the genome altered we could circumvent this. Duodenal cancers also had a significantly lower median centered percentage genome aberrated (mPGA) than colon (p=6.3 × 10-4, es=0.176), rectal (p=3 × 10-5, es=0.279), stomach (p=1.5 × 10-8, es=0.309) and oesophageal (p=1.2 × 10-11, es=0.546) adenocarcinomas. Inter-tumour heterogeneity of copy number alterations was lowest in duodenal cancers compared to other GI cancer types (p&amp;lt;2.22 × 10-16 for all and effect size &amp;gt; 0.7 for all). Within the previously published WEX cohort of small intestinal adenocarcinomas, we observed a higher proportion of clonal mutations that are neoantigens (vs not-neoantigens) in immune escaped tumours than non-escaped tumours (p=0.016) and found that small intestinal tumours are more likely to be immune escaped than colon cancers. Escaped small intestinal tumours were associated with a significantly decreased overall survival compared to non-escaped tumours (HR 2.197 (95% CI, 1.736– 46.63); p=0.009). Further, dNdS analysis indicated strong immune-mediated negative selection on clonal non-synonymous mutations in the immunopeptidome in most tumours. Conclusions: The decreased inter-tumour heterogeneity of karyotypes amongst small intestinal cancers compared to other GI cancers could indicate more restricted routes for karyotype evolution in the small intestine. Our data also suggest a more pertinent role for immune-predation than elsewhere in the GI tract. Together this may explain their lower incidence. Citation Format: Salpie Nowinski, Vickna Balarajah, Ann-Marie Baker, Riku Katainen, Christine Hughes, Qingli Guo, Luis Zapata, Eszter Lakatos, Hemant M. Kocher, Trevor A. Graham. Lower incidence of small intestinal adenocarcinomas may be due to constrained copy number karyotype and increased immune surveillance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B011.

In-hospital outcomes of acute pulmonary embolism in patients with gastrointestinal cancer: A nationwide study.

624 Background: Cancer is a well-established risk factor for the development of pulmonary embolism (PE), especially the. gastrointestinal (GI) cancers. While multiple studies have reported the burden of PE in cancer patients, recent data comparing in-hospital outcomes among different types of cancer patients are lacking. This study aimed to investigate the clinical and healthcare utilization outcomes of hospitalized patients with acute PE in the context of gastrointestinal (GI) cancers. Methods: A cross-sectional study was conducted using data from the National Inpatient Sample (2016-2020). International Statistical Classification of Diseases (ICD-10) codes were employed to identify hospitalized patients admitted with primary diagnosis acute PE. Data regarding GI cancer diagnosis along with demographic information, baseline clinical characteristics, and outcome variables, including mortality, hospital length of stay, total hospital charges, complications and risk factors were collected and analyzed. Statistical analysis was performed using the survey procedures function in STATA v.17, with statistical significance defined by the t-test at a significance level of p &lt; 0.05. Results: Among the 181,060 patients admitted with primary diagnosis of acute pulmonary embolism, 550 (0.3%) had underlying gastric cancer, 1,790 (0.98%) had pancreatic cancer, 875 (0.48%) had hepatobiliary cancer, and 2,600 (1.61%) had small intestine and colorectal cancer. Mortality was found to be significantly higher in all types of GI cancer, with gastric cancer demonstrating the highest mortality rate (10%). After adjusting for age, sex, race, payment category, comorbidities, and risk factors of PE, gastric cancer (OR 2.6; 95% CI: 1.1-6.2) and pancreatic cancer (OR 2.2; 95% CI: 1.4-3.4) were found as independent risk factors for mortality. There was no significant difference in mean length of hospital stays and mean total hospital charges in patients with or without cancer. Similarly, no significant differences were observed in complications such as requirement for mechanical ventilation, arrhythmia, cardiac arrest, need for vasopressor and thrombolysis. Conclusions: In-hospital mortality in patients with acute pulmonary embolism is significantly higher in all types of GI cancer, however; there is no significant differences in hospital length of stay and total hospital charges in patients with or without cancer.

Role of proton pump inhibitors in immune checkpoint inhibitor colitis.

743 Background: Proton pump inhibitors (PPIs) are known to be beneficial in symptomatic control of gastroesophageal reflux disease and gastritis which can be a common complication of various cancers specifically gastrointestinal (GI) cancers. Microscopic colitis development has been studied to be associated with PPI use. Immune checkpoint Inhibitor (ICI) colitis is a known adverse effect of Inhibitors of Programmed cell death 1 (PD-1) and its ligand (PD-L1). Previous studies have also shown use of PPIs and NSAIDs are common risk factors which can exacerbate ICI Colitis caused by Inhibitors of PD-1 and PD-L1. This study is designed to observe association of certain drugs especially PPIs in ICI colitis. Methods: This is a single center, retrospective, and observational study that investigated patients treated with PD-1 and PD-L1 Inhibitors for management of any type of cancer between January 2022- September 2023. A list of patients treated with PD-1 and PD-L1 inhibitors was obtained from Inpatient pharmacy records followed by retrospective chart review to look for symptoms of colitis and other medications used by each patient. Primary outcome was to observe the role of PPIs in ICI colitis. Secondary outcomes were to observe the number of patients with GI cancers on PPIs who developed colitis. We also observed the effect of NSAIDs use as a potential risk factor in the population with ICI colitis. Results: The data consisted of 93 patients of which 17 (18.3%) developed colitis. Among this population 13 (76.5%) was ICI colitis, 2 (11.7%) was diverticular colitis and 2 (11.7%) was Infectious colitis. PPI use was seen in 3 out of 13 patients (23%) with ICI colitis. Patients with any type of GI cancer who developed colitis was 5 (25%) and PPI use in ICI colitis was seen in 2 out of these 5 patients. NSAIDs use was seen in 3 (23%) patients with ICI colitis. Conclusions: We did not observe significant association between PPI use and ICI colitis. ICI use becoming increasingly common in oncologic population, larger studies may be needed to further evaluate risk factors associated with ICI colitis in this population.

Overcoming Microbiome-Acquired Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.

Gastrointestinal cancers (GICs) are one of the most recurrent diseases in the world. Among all GICs, pancreatic cancer (PC) is one of the deadliest and continues to disrupt people's lives worldwide. The most frequent pancreatic cancer type is pancreatic ductal adenocarcinoma (PDAC), representing 90 to 95% of all pancreatic malignancies. PC is one of the cancers with the worst prognoses due to its non-specific symptoms that lead to a late diagnosis, but also due to the high resistance it develops to anticancer drugs. Gemcitabine is a standard treatment option for PDAC, however, resistance to this anticancer drug develops very fast. The microbiome was recently classified as a cancer hallmark and has emerged in several studies detailing how it promotes drug resistance. However, this area of study still has seen very little development, and more answers will help in developing personalized medicine. PC is one of the cancers with the highest mortality rates; therefore, it is crucial to explore how the microbiome may mold the response to reference drugs used in PDAC, such as gemcitabine. In this article, we provide a review of what has already been investigated regarding the impact that the microbiome has on the development of PDAC in terms of its effect on the gemcitabine pathway, which may influence the response to gemcitabine. Therapeutic advances in this type of GIC could bring innovative solutions and more effective therapeutic strategies for other types of GIC, such as colorectal cancer (CRC), due to its close relation with the microbiome.

Obesity, Dietary Fats, and Gastrointestinal Cancer Risk-Potential Mechanisms Relating to Lipid Metabolism and Inflammation.

Obesity is a major driving factor in the incidence, progression, and poor treatment response in gastrointestinal cancers. Herein, we conducted a comprehensive analysis of the impact of obesity and its resulting metabolic perturbations across four gastrointestinal cancer types, namely, oesophageal, gastric, liver, and colorectal cancer. Importantly, not all obese phenotypes are equal. Obese adipose tissue heterogeneity depends on the location, structure, cellular profile (including resident immune cell populations), and dietary fatty acid intake. We discuss whether adipose heterogeneity impacts the tumorigenic environment. Dietary fat quality, in particular saturated fatty acids, promotes a hypertrophic, pro-inflammatory adipose profile, in contrast to monounsaturated fatty acids, resulting in a hyperplastic, less inflammatory adipose phenotype. The purpose of this review is to examine the impact of obesity, including dietary fat quality, on adipose tissue biology and oncogenesis, specifically focusing on lipid metabolism and inflammatory mechanisms. This is achieved with a particular focus on gastrointestinal cancers as exemplar models of obesity-associated cancers.

Current trends and future prospects of drug repositioning in gastrointestinal oncology.

Gastrointestinal (GI) cancers comprise a significant number of cancer cases worldwide and contribute to a high percentage of cancer-related deaths. To improve survival rates of GI cancer patients, it is important to find and implement more effective therapeutic strategies with better prognoses and fewer side effects. The development of new drugs can be a lengthy and expensive process, often involving clinical trials that may fail in the early stages. One strategy to address these challenges is drug repurposing (DR). Drug repurposing is a developmental strategy that involves using existing drugs approved for other diseases and leveraging their safety and pharmacological data to explore their potential use in treating different diseases. In this paper, we outline the existing therapeutic strategies and challenges associated with GI cancers and explore DR as a promising alternative approach. We have presented an extensive review of different DR methodologies, research efforts and examples of repurposed drugs within various GI cancer types, such as colorectal, pancreatic and liver cancers. Our aim is to provide a comprehensive overview of employing the DR approach in GI cancers to inform future research endeavors and clinical trials in this field.

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer

BackgroundAdipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy.For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia.MethodsWe considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases.We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5.ResultsWe found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027).ConclusionIn our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type.

Effect of patient and diagnostic intervals on the risk of advanced stage in Indian patients with seven types of gastrointestinal cancers: A retrospective cohort study

ObjectivesAdvanced stage is linked to prolonged patient and diagnostic interval for gastrointestinal (GI) cancers. However, objective evidence of this fact is not so forthcoming. Our aim was to study the effect of these intervals on the risk of advanced stage for GI cancers. MethodsWe performed this retrospective cohort study to analyse the effect of patient and diagnostic intervals on final stage in seven types of GI cancers, during 2013 and 2022. Two groups of stage: early (TNM- 0, I, II) and advanced (TNM- III, IV), were formed. Outcome studied was interdependence between patient and diagnostic intervals and incidence of advanced stage. Binary logistic regression was applied to calculate odds ratio of having an advanced versus early stage as a function of duration of these delays, in the whole cohort.We used restricted cubic splines with five knots to study flexible and non-monotonic pattern of association between these delays and stage. ResultsIn whole cohort of 1859 patients, median patient and diagnostic intervals of early and advanced cancers were 21 and 26 days and 120 and 45 days, respectively. There was a positive association between patient interval and advanced stage (odds ratio [OR], 1.04, confidence interval [CI], 1.035 to 1.045; P < 0.001) and negative association between diagnostic interval and advanced stage (odds ratio, 0.98, CI, 0.976 to 0.998; P-0.017), among all gastrointestinal cancers combined. Increased risk of advanced stage started from day one of patient interval and for diagnostic interval there was an initial decrease followed by subsequent increase in the risk of advanced stage beyond 26 days of diagnostic interval. ConclusionsLonger patient and diagnostic intervals increase the risk of advanced stage in gastrointestinal cancers.

Analysis of immune-related adverse events in gastrointestinal malignancy patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors are becoming an increasingly common treatment for advanced gastrointestinal cancer, but the possibility of immune-related adverse events has raised concerns. This study aimed to evaluate the risks of immune-related adverse events between patients who received immune checkpoint inhibitors and those who received chemotherapy among different types of gastrointestinal cancer. The study utilized data from the multicenter TriNetX database in the United States covering the period between 2015 and 2022. Hazard ratios and 95% confidence intervals were used to describe the relative hazard of immune-related adverse events based on comparing time-to-event rates. Our study revealed that the incidence of immune-related adverse events was significantly higher in patients who received immune checkpoint inhibitors and chemotherapy compared to those who received chemotherapy only in treating gastrointestinal cancer. CTLA-4 inhibitors tended to have a higher rate of immune-related adverse events compared to PD-1/PD-L1 inhibitors. Our study found a lower mortality rate among patients who developed immune-related adverse events compared to those who did not after propensity score matching (HR, 0.661; 95% CI 0.620-0.704; p < .01). We provide important real-world data on the incidence and impact of immune-related adverse events in patients with advanced gastrointestinal cancer treated with immune checkpoint inhibitors. Our study's results support clinicians in making informed decisions about the potential benefits and risks of immune checkpoint inhibitor therapy for patients with gastrointestinal cancer.

Study on direct medical cost of inpatient treatment for gastrointestinal cancers at Hue University of Medicine and Pharmacy Hospital

Background: Gastrointestinal cancers, including liver cancer, colorectal cancer, and stomach cancer, are the most common cancers in the world as well as in Vietnam, posing a leading threat to human health. The cost of treating these cancers is a major problem that burdens not only patients but also healthcare systems. The study aims to analyze treatment costs for the four most common types of gastrointestinal cancer nowadays. Materials and method: A cross-sectional study was conducted to collect data from 300 medical records of inpatients with gastrointestinal cancers at the hospital of Hue University of Medicine and Pharmacy in 2021. Results: The average direct medical cost per inpatient admission was 14,239,915 VND (95% CI: 12,502,135 - 15,977,695 VND) in 2021. The cost per inpatient admission for liver cancer treatment was the highest, by 20,267,780 VND (95% CI: 16,036,541- 24,499,018 VND). The cost of drugs accounted for the highest proportion (38.1%), followed by the cost of medical supplies (14.7%). There is a statistically significant difference between the median cost of groups classified by age, metastasis, comorbidity, and length of hospital stay. Conclusion: Direct medical costs for patients with four common types of gastrointestinal cancers impose a considerable economic burden on patients and the health system. Further cost analysis studies need to be conducted. Strategies to decrease the economic burden of gastrointestinal, such as screening programs, and improving awareness of the prevention of cancer should be developed in Vietnam. Key words: direct medical costs, gastrointestinal cancer, Hospital of Hue University of Medicine and Pharmacy.