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Cryptosporidium parvum (C. parvum) is an apicomplexan protozoan known as a frequent cause of diarrhea. Because of its severe outbreaks and the association with different types of gastrointestinal cancers, it became an urgent need to develop effective solutions against that parasite. In the current study, the complete proteome of C. parvum was analyzed, and after applying several filtration steps, two proteins, namely Glycoprotein 60 (gp40/15) and thrombospondin-related adhesive protein (TRAP C-1), were selected as the protein candidates for epitope prediction. Next, CTL, HTL and BCL epitopes of each protein candidate were defined, and the best epitopes of each category were assembled alongside suitable linkers and adjuvants to initiate a potential multitope vaccine construct finally. That construct was evaluated for several properties, including its antigenicity, allergenicity, stability, secondary and tertiary structure, and the ability of that 3D predicted model to bind to TLR4. Furthermore, the stability of the constructed vaccine ligand in the TLR4 receptor was deeply investigated through a molecular dynamics simulation. The current study describes the stages of the multitope construct design. It demonstrates the results of that construct computational evaluation where the generated scores support the nomination of that potential vaccine as a solution for C. parvum infection, and further wet lab experiments are required to validate our current findings. [ABSTRACT FROM AUTHOR]

Background and Purpose: Gastrointestinal tumours overexpress voltage‐gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti‐tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. Experimental Approach: Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch‐clamp experiments. The anti‐tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. Key Results: High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration‐ and use‐dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down‐regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. Conclusion and Implications: Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies. [ABSTRACT FROM AUTHOR]

Reversing cancer cachexia remains a challenge. Genetic biomarkers for the early detection of the disease have been explored in order to enable the implementation of preventive measures. We therefore genotyped candidate genes based on cachexia phenotype and quantified adiponectin and GDF-15 levels in cachectic patients with gastrointestinal cancer. Patients with a diagnosis of gastrointestinal cancer were divided into a cachectic and a non-cachectic group after the start of chemotherapy. A control group (no cancer) was also included. We genotyped the following single nucleotide polymorphisms (SNPs) by quantitative PCR: FOXO3 (rs1935949), FOXO3 (rs4946935), ACVR2B (rs2268757), and SELP (rs6136). In addition, we quantified adiponectin and GDF-15 levels by ELISA. The rs2268757 SNP in the ACVR2B gene was associated with the weight loss phenotype in cachectic patients with gastrointestinal cancer (non-cachectic, P = 0.004). Plasma adiponectin levels were higher in cachectic patients compared to controls (P = 0.01) and non-cachectic patients (P = 0.004). GDF-15 was also elevated in cachectic patients compared to controls (P < 0.0001) and non-cachectic patients (P = 0.001). Analysis by sex showed elevated adiponectin levels in men (control, P = 0.01) and cachectic women (control, P = 0.04; non-cachectic, P = 0.01), as well as elevated GDF-15 levels in men (control, P = 0.002) and cachectic women (control, P = 0.002; non-cachectic, P = 0.007). However, there was no significant difference in the levels of these cytokines between cachectic men and women. The results suggest the rs2268757 SNP in the ACVR2B gene, adiponectin, and GDF-15 as potential biomarkers of cachexia in gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

Background: Patients with gastrointestinal cancer have a higher risk of malnutrition and postoperative infection. Objective: To investigate the nutritional status of patients with gastrointestinal cancers and factors for postoperative infections. Method: Based on the nutritional risk status, 294 patients with gastrointestinal tumours were divided into a nutritional risk group and a non-nutritional risk group, and the differences between the two groups were compared. Results: Among the included patients, 128 were at preoperative nutritional risk (43.54%); there were significant differences between the two groups in terms of age (66.25 ± 11.73 vs. 58.36 ± 10.41 years, P < 0.001), percentage of gastric cancers (39.84% vs. 28.92%, P = 0.049), percentage of stage IV tumours (60.16% vs. 45.18%, P = 0.011), total protein (64.90 ± 6.82 vs. 67.21 ± 7.41 g/L, P = 0.007), albumin (38.32 ± 4.74 vs. 41.61 ± 5.10 g/L, P < 0.001) and haemoglobin (112.72 ± 22.63 vs. 125.11 ± 22.79 g/L, P < 0.001). Multivariate logistic regression analysis showed that risk factors for postoperative infections in patients included age ≥ 60 years (odds ratio [OR] = 2.266 95%CI = 1.357–4.134), Nutrition Risk Screening (NRS)-2002 score ≥ 3 (OR = 2.183, 95%CI = 1.218–4.102), alcohol history (OR = 2.505, 95%CI = 1.370–4.683), comorbid diabetes mellitus (OR = 2.110, 95%CI = 1.381–4.023) and surgical time ≥ 6 h (OR = 2.446, 95%CI = 1.359–4.758). Conclusion: Patients with gastrointestinal cancers are at high incidence of preoperative nutritional risk, and those with an NRS-2002 score of > 3, history of alcohol consumption and surgical time of > 6 h have a higher risk of postoperative infections. [ABSTRACT FROM AUTHOR]

Background Aims and Methods Results Conclusions Dumping syndrome is a complex of gastrointestinal symptoms originally studied in peptic ulcer surgery patients. At present, it is most prevalent in patients who underwent bariatric, upper gastrointestinal cancer or anti‐reflux surgery. The symptom pattern comprises early and late dumping symptoms. Several management options have been reported including nutritional, pharmacological and surgical approaches.In this study, we aimed to review the current evidence on dumping syndrome definition, diagnosis and treatment, including preliminary data from newer pharmacological studies.Current pathophysiological concepts and analyses of provocative tests has led to a clear definition of dumping syndrome, including both early and late dumping symptoms. The term postbariatric hypoglycemia represents a limited focus on late dumping only. The diagnosis relies on recognition of symptoms and signs in a patient with appropriate surgical history; and can be confirmed by provocative testing or registration of spontaneous hypoglycemia. The initial treatment focuses on dietary intervention, to which meal viscosity enhancers and/or the glycosidase inhibitor acarbose can be added. The most effective therapy is the use of short‐ or long‐acting somatostatin analogues, which is however expensive and entails side effect issues. In case of refractory hypoglycemia, diazoxide or SGLT2 inhibitors can be considered, based on limited evidence. In refractory patients, continuous enteral feeding or (rarely) surgical reinterventions have been advocated, although not supported by solid evidence. Therapies under current evaluation include the broad‐spectrum somatostatin analogue pasireotide, GLP‐1 receptor antagonists, GLP‐1 receptor agonists and administration of stable forms of glucagon are currently under study.Dumping syndrome is a well‐defined but probably under‐diagnosed complication of upper gastrointestinal, especially bariatric, and surgeries. Diagnosis is confirmed by a provocative test and incremental therapies starting with diet, adding meal viscosity enhancers or glycosidase inhibitors and adding somatostatin analogues in refractory cases. A number of emerging therapies targeting intestinal propulsion, peptide hormone effects and hypoglycemic events are under evaluation. [ABSTRACT FROM AUTHOR]

There are currently many clinical issues plaguing digestive oncologists, including the impact of dietary habits on the occurrence of early gastrointestinal cancer, the association between irritable bowel syndrome, ulcerative colitis, and early gastrointestinal cancer, the expected changes in gastrointestinal cancer after IBS, IBD, and susceptibility gene mutations, and the mechanisms by which susceptibility gene mutations in gastrointestinal cancer lead to different diseases. Meanwhile, as a carcinogen, betel nut is also prone to cancer and emotional disorders, and there are also many doctor-patient conflicts in the current clinical treatment of digestive tract tumors. To address the aforementioned issues, the research team analyzed dietary habits data using SOM clustering algorithm and isolated forest algorithm. Based on bioinformatics, new therapies have been developed for the pathogenesis and immune pathways of various cancers in the digestive system. Using network pharmacology methods, explore the toxicological mechanism of betel nut and its mechanism in mediating emotional disorders. Molecular docking is used to elucidate drug prediction. Based on four AI algorithms, the occurrence of gastrointestinal cancer was predicted through dietary habits. Using computer vision technology to address the deficiencies in early clinical reporting of cancer. This article provides clinical doctors with new treatment tools. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions In immunochemical fecal occult blood test (iFOBT) positive subjects, colonoscopy screening can detect colorectal cancers and advanced adenomas, yet most iFOBT‐positive subjects find no relevant lower gastrointestinal lesions. Limited data are available on upper gastrointestinal (UGI) cancer risk in iFOBT‐positive patients. This study investigated the incidence of UGI malignancies diagnosed within 3 years post‐colonoscopy after a positive iFOBT.Retrospective analysis of iFOBT‐positive patients aged 50–75 years who underwent a colonoscopy at a single institution. All patients with a diagnosis of UGI cancer within 3 years post‐colonoscopy were identified by linking with the Queensland Cancer Register. This was used to compare to the geographical population aged 50–74 years based on the Australian Bureau of Statistics and Queensland Cancer Council data.From 1748 eligible participants, 0.23% (95% confidence interval [CI] 0.06–0.58) were diagnosed with UGI cancer within 3 years post‐colonoscopy. This indicates an esophageal cancers rate of 114.42 per 100 000 (95% CI 100.56–298.28) and gastric cancer rate of 57.21 per 100 000 (95% CI 55.76–261.12). Of the patients with a UGI cancer, 75% would have had an unexplained iFOBT. Annual incidence for the same geographic region, ages, and period for the combined esophageal and gastric cancer was 36.08 per 100 000 (95% CI 32.87–39.52).Among individuals with a positive iFOBT in a bowel cancer screening program, the rates of gastric and esophageal cancers were 2.7 and 7.5 times higher than the general population. Adding gastroscopy to a colonoscopy for iFOBT‐positive patients in cancer surveillance programs may be justifiable. [ABSTRACT FROM AUTHOR]

Introduction: Malignancy-related ascites (MRA) is a common serious complication of many advanced malignant tumors with high morbidity and mortality. The high hospital expenditures induced by unplanned readmission in patients with MRA have become an urgent issue to the public. We aimed to overall assess the unplanned early readmission rate of patients with MRA and explore the potential risk factors for such readmission. Methods: A retrospective cohort study based on 2018 Nationwide Readmissions Database was performed and patients with MRA were recruited into the analysis. The primary outcome was unplanned 30-day readmission rate and inpatient outcomes. The multivariate logistic regression analysis was performed to evaluate the potential risk factors for such early readmission. Results: Data obtained from 32,457 patients with MRA were analyzed, and of these 7,799 individuals (24.03%) were unplanned readmitted within 30-day follow-up. The mortality rate in the readmitted population was 15.15%. Patients at younger age were at a higher risk of readmission. The morbidities including hypertension (OR=1.117, 95%CI: 1.054-1.184), hyperlipemia (OR=1.075, 95%CI: 1.009-1.146) and diabetes (OR=1.118, 95%CI: 1.053-1.188), gastrointestinal malignancies and peritoneal procedure significantly increased the risk of 30-day readmission in patients with MRA. Discussion: More than one in five patients with MRA was unplanned readmitted within 30-day follow-up. The above risk factors should be timely intervened and the corresponding medical care should be strengthened in patients with MRA to lessen the unplanned readmission and improve the readmission outcomes. [ABSTRACT FROM AUTHOR]

Oncogenesis is a complex and multi-step process, controlled by several factors including epigenetic modifications. It is considered that histone modifications are critical components in the regulation of gene expression, protein functions, and molecular interactions. Dysregulated post-translationally modified histones and the related enzymatic systems are key players in the control of cell proliferation and differentiation, which are associated with the onset and progression of cancers. The most of traditional investigations on cancer have focused on mutations of oncogenes and tumor suppressor genes. However, increasing evidence indicates that epigenetics, especially histone post-translational modifications (PTMs) play important roles in various cancer types. Mass spectrometry-based proteomic approaches have demonstrated tremendous potential in PTMs profiling and quantitation in different biological systems. In this paper, we have made a proteomics-based review on the role of histone modifications involved in gastrointestinal cancers (GCs) tumorigenesis processes. These alterations function not only as diagnostic or prognostic biomarkers for GCs, but a deeper comprehension of the epigenetic regulation of GCs could facilitate the treatment of this prevalent malignancy through the creation of more effective targeted therapies. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers are the most common malignancies, while surgical intervention remains the sole therapeutic approach offering the possibility of a definite cure for cancer. Perioperative anxiety negatively impacts the recovery of GI cancers. Recently, mounting studies have demonstrated that proper nursing interventions may alleviative perioperative anxious illnesses in patients with GI cancers. We conducted a first comprehensive review to summarize all the current evidence on this topic. After a systematically search in the six common databases, eighteen relevant studies were included for further analysis. The present review highlighted that there is a high prevalence of perioperative anxiety in patients with GI cancers (e.g., colorectal cancer, gastric/stomach cancer, hepatocellular carcinoma, gallbladder cancer, and esophageal cancer), while specific nursing interventions are the reliable methods to reduce postoperative anxiety. These nursing strategies include, but are not limited to, therapeutic listening intervention, implementing perioperative music, predictive nursing, progressive relaxation exercises, psychological interventions in the nursing care, comprehensive nursing, continuous nursing care, video-based nursing education, multidisciplinary cooperative continuous care, accelerated rehabilitation nursing, TCM nursing, evidence-based early warning nursing, target nursing care, and high-quality nursing. Since several limitations existed in the eligible studies as well as in this review, a well-designed multicenter RCT with large sample size is still warranted for the confirmation of nursing intervention for managing perioperative anxiety in patients with GI cancers. Also, future studies should focus on the long-term effects of relevant interventions, specific patient populations, multidisciplinary approaches, technological innovations, and educational programs. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer has emerged as a significant global health concern due to its high incidence and mortality, limited effectiveness of early detection, suboptimal treatment outcomes, and poor prognosis. Metabolic reprogramming is a prominent feature of cancer, and fatty acid metabolism assumes a pivotal role in bridging glucose metabolism and lipid metabolism. Fatty acids play important roles in cellular structural composition, energy supply, signal transduction, and other lipid‐related processes. Changes in the levels of fatty acid metabolite may indicate the malignant transformation of gastrointestinal cells, which have an impact on the prognosis of patients and can be used as a marker to monitor the efficacy of anticancer therapy. Therefore, targeting key enzymes involved in fatty acid metabolism, either as monotherapy or in combination with other agents, is a promising strategy for anticancer treatment. This article reviews the potential mechanisms of fatty acid metabolism disorders in the occurrence and development of gastrointestinal tumors, and summarizes the related potential biomarkers and anticancer strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with treated solid tumors (TST) are a highly heterogeneous and difficult-to-treat population due to the risk of disease progression/recurrence or infection. Methods: We conducted an observational, retrospective, single-center study at the Dermatology Clinic of Turin with a focus on the special population of cancer patients with psoriasis treated with biologics. Results: As of July 2023, 52 psoriatic patients with a prior/concomitant history of malignancy had taken biologic drugs. The median age was 67 years, and the median age of cancer onset was 55 years. The most common tumors were gastrointestinal cancer and melanoma. After the tumor diagnosis, 61% received an anti-IL17 drug; 37 patients continued the initiated biologic therapy, while 12 switched drugs due to secondary inefficacy. The estimated biologic DS was 55.6% at 50 months. Evidence suggests that IL-17 is a key pathogenic factor involved in tumorigenesis, resulting in a lower risk of malignancies in subjects managed with IL-17 inhibitors. Similarly, IL-23 plays a role in suppressing innate immunity and promoting tumor and metastases development. This is a consistent real-life case series that support the use of biologic drugs in patients with TST. Conclusions: IL-23 and IL-17 inhibitors, being immunomodulators rather than immunosuppressants, may be a safe option for patients in an active oncological setting and for immune-correlated adverse events. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancers are still the leading cause of death worldwide. This is related, among other things, to the non-specific symptoms, especially in the initial stages, and also to the limited possibilities for treatment. Therefore, research is still being conducted to improve the detection of this type of cancer and increase the effectiveness of therapy. The potential application of natural compounds in cancer management deserves special attention. In the group of such products, there are polyphenolic compounds that reveal, e.g., anti-oxidative, anti-carcinogenic, anti-inflammatory, anti-diabetic, and neuroprotective properties. One of these polyphenols is rosmarinic acid, commonly found in plants such as the Boraginaceae and Nepetoideae subfamilies of the Lamiaceae (mint) family. A number of studies have considered the positive effects of rosmarinic acid in the treatment of many cancers, including gastrointestinal ones such as oral, stomach, pancreas, colon, and liver cancers. The main aim of this paper was to summarize the mechanisms of action of rosmarinic acid in gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Objectives: There have been significant advances in the management of large (≥20 mm) laterally spreading tumors (LSTs) or nonpedunculated colorectal polyps; however, there is a lack of clear consensus on the management of these lesions with significant geographic variability especially between Eastern and Western paradigms. We aimed to provide an international consensus to better guide management and attempt to homogenize practices. Methods: Two experts in interventional endoscopy spearheaded an evidence‐based Delphi study on behalf of the World Endoscopy Organization Colorectal Cancer Screening Committee. A steering committee comprising six members devised 51 statements, and 43 experts from 18 countries on six continents participated in a three‐round voting process. The Grading of Recommendations, Assessment, Development and Evaluations tool was used to assess evidence quality and recommendation strength. Consensus was defined as ≥80% agreement (strongly agree or agree) on a 5‐point Likert scale. Results: Forty‐two statements reached consensus after three rounds of voting. Recommendations included: three statements on training and competency; 10 statements on preresection evaluation, including optical diagnosis, classification, and staging of LSTs; 14 statements on endoscopic resection indications and technique, including statements on en bloc and piecemeal resection decision‐making; seven statements on postresection evaluation; and eight statements on postresection care. Conclusions: An international expert consensus based on the current available evidence has been developed to guide the evaluation, resection, and follow‐up of LSTs. This may provide guiding principles for the global management of these lesions and standardize current practices. [ABSTRACT FROM AUTHOR]

Simple Summary: This study involved 2745 participants from a southern Italian cohort. The objective was to investigate the link between the consumption of extra virgin olive oil and the risk of mortality from all causes and, in particular, from gastrointestinal cancers and other cancers. The study found that individuals who consumed more than 50 g of extra virgin olive oil per day had a 60 percent lower risk of death from gastrointestinal cancers than those who consumed less than 30 g per day. Furthermore, daily consumption of 50 g of extra virgin olive oil was associated with a 50 percent lower risk of death from other cancers compared to the lowest consumption category. This study concluded that higher olive oil consumption in this cohort of Italian Mediterranean adults was linked to a reduced risk of cancer and all-cause mortality, probably due to the health benefits of the Mediterranean diet. Background/Objectives: This study investigates the association between extra virgin olive oil (EVOO) consumption and mortality risk in a cohort of Italian adults adhering to the Mediterranean diet. Methods: In a 17-year follow-up study involving participants from Castellana Grotte, Italy (2005–2023), we analyzed dietary intake and mortality data. Participants were categorized into three EVOO consumption groups: <30 g/day, 30–50 g/day, and >50 g/day. Mortality Hazard Ratios (HR) and Subdistribution Hazard Ratios (SHR) were calculated to assess the relationship between EVOO intake and all-cause and cancer mortality. Results: Higher EVOO consumption was associated with significantly reduced cancer and all-cause mortality. Specifically, the daily intake of 30–50 g of EVOO was linked to a 24% lower risk of all-cause mortality (HR 0.77; 95% CI 0.63–0.93), while the consumption of more than 50 g/day was associated with a 20% reduction (HR 0.80; 95% CI 0.65–0.98). The most pronounced benefit was observed for gastrointestinal cancers, with a 60% lower mortality risk for those consuming over 50 g/day (SHR 0.39; 95% CI 0.21–0.73). A 50% reduction in mortality risk from other cancers was also noted for the highest consumption category (SHR 0.50; 95% CI 0.31–0.81). Conclusions: The findings support the beneficial role of EVOO in reducing cancer mortality, particularly with higher consumption levels. The results underscore EVOO's potential as a dietary intervention for cancer prevention, aligning with the Mediterranean diet's overall health benefits. Further research is needed to confirm these findings and explore the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Recent advances in tumor immunology and molecular drug development have ushered in a new era of cancer immunotherapy. Immunotherapy has shown promising results for several types of tumors, such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin's lymphoma. Similarly, efforts have been made to develop immunotherapies such as adoptive T-cell transplantation, peptide vaccines, and dendritic cell vaccines, specifically for gastrointestinal tumors. However, before the advent of immune checkpoint inhibitors, immunotherapy did not work as well as expected. In this article, we review immunotherapy, focusing on cancer vaccines for gastrointestinal tumors, which generally target eliciting tumor-specific CD8 + cytotoxic T lymphocytes (CTLs). We also review various vaccine therapies and describe the relationship between vaccines and adjuvants. Finally, we discuss prospects for the combination of immunotherapy with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor 15 (GDF15), a stress‐responsive cytokine from transforming growth factor superfamily, is highly expressed in mammalian tissues, including pancreas, stomach and intestine under pathological conditions. In particular, elevated levels of GDF15 might play an important role in the development and progression of various gastrointestinal cancers (GCs), suggesting its potential as a promising target for disease prediction and treatment. Methods: In this review, systematic reviews addressing the role of GDF15 in GCs were updated, along with the latest clinical trials focussing on the GDF15‐associated digestive malignancies. Results: The multiple cellular pathways through which GDF15 is involved in the regulation of physiological and pathological conditions were first summarized. Then, GDF15 was also established as a valuable clinical index, functioning as a predictive marker in diverse GCs. Notably, latest clinical treatments targeting GDF15 were also highlighted, demonstrating its promising potential in mitigating and curing digestive malignancies. Conclusions: This review unveils the pivotal roles of GDF15 and its potential as a promising target in the pathogenesis of GCs, which may provide insightful directions for future investigations. [ABSTRACT FROM AUTHOR]

Background: The frequency of major cancer surgery in the elderly (≥80 years) has increased concomitantly with the rise in average age of the population. We assessed early postoperative mortality following hepato-pancreato-biliary (HPB) and gastrointestinal (GI) procedures for common malignancies stratified by age. Methods: The National Cancer Database (2004-2017) was queried for patients who underwent resection for GI (gastroesophageal and colorectal) or HPB (pancreatic adenocarcinoma, biliary tract, and primary liver) cancers. We compared early postoperative mortality (30 d and 90 d) stratified by age (65-79 vs ≥80 years) and procedure, and compared survival outcomes by age and operative vs nonoperative management. Results: A total of 709,358 patients were included. The 30-day mortality ranged from 1.8% to 5.8% among patients 65-79 years and from 3.2% to 12.4% among patients ≥80 years depending on procedure. The 90-day mortality ranged from 3.6% to 10.6% in patients 65-79 years compared to 8.4%-21.0% among patients ≥80 years. The overall 90-day mortality was 5.2% for patients 65-79 years and 12.0% for patients ≥80 years (P < .001). Age ≥80 was associated with worse survival among operatively managed patients with each upper GI, HPB, and lower GI malignancy relative to younger patients on multivariable analysis. However, operative management of patients ≥80 years was associated with improved survival relative to nonoperative management. Discussion: Elderly patients suffer higher postoperative mortality after major GI and HPB cancer surgery, but operative management is associated with improved survival among patients ≥80 years as compared to nonoperative management. These data are important to contextualize when counseling elderly patients on their treatment options for localized GI and HPB cancers. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBDs) pose an increased risk of gastrointestinal cancer with especially worse prognosis. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes in selected patients with colorectal peritoneal metastases. Little published data describes the outcomes of CRS/HIPEC in IBD patients. Methods: We performed a retrospective review of a prospectively maintained CRS/HIPEC database. Outcomes in patients with and without IBD were compared for short-term outcomes such as hospital/intensive care unit stay, blood loss/transfusions, complications, and reoperations. We also examined oncological outcomes including recurrence, overall (OS), and disease-free survival (DFS). Results: We identified 232 patients that underwent CRS/HIPEC for colorectal or small bowel adenocarcinoma, of which 10 were with IBD. Patients with IBD had lower ASA (p=0.005), less hypertension (p=0.033), and 30% small bowel primary compared to none in the non-IBD cohort (p<0.001). Otherwise, demographic and perioperative characteristics were similar between the groups. The median peritoneal cancer index (PCI) was 7 and similar between the cohorts (p=0.422). Extent of organ resections and peritonectomies performed were similar. Complications occurred in 60.3% of patients (21.2% major), similar between the groups (p=0.744 and p=0.444, respectively). Reoperation rate of 27% was similar between groups (p=0.097). The median OS in the IBD cohort was 19.6 vs 53.2 months in the non-IBD cohort (p = 0.056). The median DFS in the IBD cohort was 4.9 vs 9.4 months in the non-IBD cohort (p=0.174). Discussion: Cytoreductive surgery and heated intraperitoneal chemotherapy in patients with IBD has similar complication profile and trended towards poorer oncological outcomes as CRS/HIPEC in non-IBD patients. [ABSTRACT FROM AUTHOR]

The contribution of suboptimal diets to gastrointestinal (GI) cancer incidence globally remains unquantified, and we aimed to evaluate it. Comprehensive meta-analyses and rigorous evidence-grading assessment identified the associations between suboptimal diets and 6 GI cancers and their subtypes. A comparative risk assessment model was used to estimate the proportional attributable burden and attributable rate of GI cancers to suboptimal diets by using the corroborative association estimates. In addition, correlation assessments with the Sociodemographic Index were carried out. In 2018, 21.5% (95% uncertainty interval, 19.1%–24.5%) of incident GI cancer cases globally were attributable to suboptimal diets, maintaining a relatively stable proportion since 1990 (22.4%; 19.7%–25.6%), whereas the absolute diet-attributable cases doubled from 580,862 (510,658–664,076) in 1990 to 1,039,877 (923,482–1,187,244) in 2018. Excessive processed meat consumption (5.9%; 4.2%–7.9%), insufficient fruit intake (4.8%; 3.8%–5.9%), and insufficient whole grain intake (3.6%; 2.8%–5.1%) were the most significant dietary risk factors in 2018, a shift from 1990 when the third major concern was insufficient nonstarchy vegetable intake. In addition, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in both 1990 (31.6%; 27.0%–37.4%) and 2018 (31.6%; 27.3%–36.5%), and a positive correlation (P <.001) between the Sociodemographic Index and the attributable GI cancer incidence was observed. Although the proportional attributable GI incidence remains relatively stable, the doubling of absolute cases from 1990 to 2018, along with the discrepancies among urbanicity and countries/regions, informs dietary priorities and more targeted preventive measures. [Display omitted] Although the proportion of diet-attributable gastrointestinal cancer incidence remained stable over 28 years, the absolute number of cases doubled, with variations in this burden observed among different cancer types, countries, regions, and demographic groups. Intensive and more targeted preventive measures are warranted. [ABSTRACT FROM AUTHOR]

Purpose The aim of the present study is to explore the possible association between periodontitis and upper gastrointestinal (UGI) cancers, including esophageal and gastric cancers, utilizing the Mendelian randomization method. Methods In this research, we utilized the Mendelian randomization method to examine the causal association between periodontitis and UGI cancers. Genome-wide association studies data for periodontitis were obtained from the Gene-Lifestyle Interactions in Dental Endpoints consortium, while UGI cancers' data were accessed from FinnGen's Biobank. After rigorously screening instrumental variables for periodontitis, we analyzed them with UGI cancers primarily using the inverse variance weighted. Finally, to identify outliers, the results were subjected to a leave-one-out sensitivity analysis. Results Inverse variance weighted (fixed effect) results revealed that periodontitis is a risk factor for gastric cancer (OR = 1.7735, 95% CI: 1.1576 to 2.7170, P  = 0.0085). As for esophageal cancer, no statistically significant correlation was observed. Furthermore, no outliers were detected in any of the results. Conclusion Our two-sample Mendelian randomization study obviously demonstrates a significant positive association between periodontitis and gastric cancer, while no statistically significant correlation was found for esophageal cancer. What is already known on this topic? Observational studies have indicated that patients with periodontitis have a higher overall incidence of cancer compared to individuals without periodontitis. However, traditional analytical methods have made it difficult to determine whether these associations are independent of confounding factors. Therefore, further evidence for causality may need to be obtained through a randomized trial, such as a Mendelian randomization (MR) analysis. What this study adds? Our two-sample MR (TSMR) study offers compelling genetic evidence, suggesting that periodontitis increases the risk of gastric cancer. How this study might affect research, practice, or policy? The results of this study have the potential to illuminate the relationship between periodontitis and gastric cancer, providing fresh insights into strategies for the prevention and management of this type of cancer. [ABSTRACT FROM AUTHOR]

Background: The interactions between cancer cells and tumor‐associated macrophages (TAMs) via microRNAs (miRNAs) play crucial roles in malignant potential and drug resistance. However, it remains unclear how lenvatinib‐resistant hepatocellular carcinoma (LR HCC) promotes TAM tumor biology. Here we investigated the crosstalk between LR HCC cells and TAMs for cancer progression and lenvatinib resistance, focusing on an exosomal miRNA. Methods: We used two bioinformatics software programs to identify miRNAs that target PTEN in gastrointestinal cancers, then investigated exosomal miRNA expression in LR HCC conditioned medium (CM). After modifying TAMs with LR HCC CM (LR TAM), macrophage phenotype and PTEN‐Nrf2 signaling pathway component expression were analyzed in LR TAMs. The malignant potential and drug resistance were investigated in naïve HCC cells cultured with LR TAM CM. Results: LR HCC cells highly induced M2‐like properties in macrophages compared with naïve HCC cells. Exosomal miR‐301a‐3p expression was increased in LR HCC CM, with higher activation of the PTEN/PI3K/GSK3β/Nrf2 signaling pathway in LR TAMs. Naïve HCC cells were educated with LR TAM CM to promote malignant potential and lenvatinib resistance. Inhibition of exosomal miR‐301a‐3p prevented the malignant potential of LR TAMs. Activation of Nrf2 signaling by LR HCC cell‐derived exosomal miR‐301a‐3p skewed the transformation of macrophages to the M2 phenotype. Conclusion: Our study provides new findings on the role of miR‐301a‐3p, suggesting it is a promising therapeutic target to improve HCC lenvatinib resistance. [ABSTRACT FROM AUTHOR]

Gastrointestinal tumors are the main causes of death among the patients. These tumors are mainly diagnosed in the advanced stages and their response to therapy is unfavorable. In spite of the development of conventional therapeutics including surgery, chemotherapy, radiotherapy and immunotherapy, the treatment of these tumors is still challenging. As a result, the new therapeutics based on (nano)biotechnology have been introduced. Hydrogels are polymeric 3D networks capable of absorbing water to swell with favorable biocompatibility. In spite of application of hydrogels in the treatment of different human diseases, their wide application in cancer therapy has been improved because of their potential in drug and gene delivery, boosting chemotherapy and immunotherapy as well as development of vaccines. The current review focuses on the role of hydrogels in the treatment of gastrointestinal tumors. Hydrogels provide delivery of drugs (both natural or synthetic compounds and their co-delivery) along with gene delivery. Along with delivery, hydrogels stimulate phototherapy (photothermal and photodynamic therapy) in the suppression of these tumors. Besides, the ability of hydrogels for the induction of immune-related cells such as dendritic cells can boost cancer immunotherapy. For more specific cancer therapy, the stimuli-responsive types of hydrogels including thermo- and pH-sensitive hydrogels along with their self-healing ability have improved the site specific drug delivery. Moreover, hydrogels are promising for diagnosis, circulating tumor cell isolation and detection of biomarkers in the gastrointestinal tumors, highlighting their importance in clinic. Hence, hydrogels are diagnostic and therapeutic tools for the gastrointestimal tumors. [ABSTRACT FROM AUTHOR]

This study aimed to develop a machine learning (ML) model for predicting pulmonary embolism (PE) in patients with gastrointestinal cancers, a group at increased risk for PE. We conducted a retrospective, multicenter study analyzing patients who underwent computed tomographic pulmonary angiography (CTPA) between 2010 and 2020. The study utilized demographic and clinical data, including the Wells score and D-dimer levels, to train a random forest ML model. The model's effectiveness was assessed using the area under the receiver operating curve (AUROC). In total, 446 patients from hospital A and 139 from hospital B were included. The training set consisted of 356 patients from hospital A, with internal validation on 90 and external validation on 139 patients from hospital B. The model achieved an AUROC of 0.736 in hospital A and 0.669 in hospital B. The ML model significantly reduced the number of patients recommended for CTPA compared to the conventional diagnostic strategy (hospital A; 100.0% vs. 91.1%, P < 0.001, hospital B; 100.0% vs. 93.5%, P = 0.003). The results indicate that an ML-based prediction model can reduce unnecessary CTPA procedures in gastrointestinal cancer patients, highlighting its potential to enhance diagnostic efficiency and reduce patient burden. [ABSTRACT FROM AUTHOR]

Pulmonary enteric adenocarcinoma (PEAC), an uncommon variant of lung cancer, presents significant diagnostic challenges due to its overlapping characteristics with colorectal adenocarcinomas. We present a case of a 55-year-old non-smoking female patient diagnosed with PEAC. The patient's initial symptoms included fever, cough, and sputum production, with air space consolidation on CT, leading to an initial diagnosis of pneumonia. Sputum culture after admission showed no growth of bacteria and fungi. Anti-inflammatory therapy was not ideal. Subsequent bronchoscopy with endobronchial ultrasound and biopsy confirmed the diagnosis of PEAC. Gastroscopy and colonoscopy yielded negative results, and a PET/CT scan revealed an FDG-avid lesion in the right middle lobe, with no other significant hypermetabolic gastrointestinal lesions, thereby excluding an extrapulmonary primary gastrointestinal malignancy. The patient was ultimately staged as PEAC (T4N1M0, stage IIIb). She declined anti-tumor therapy and experienced clinical deterioration during follow-up. This case report expands the radiological spectrum of PEAC, adds to the limited literature, and emphasizes the role of 18F-FDG PET/CT in diagnosing such diseases. It also underscores the importance of a multidisciplinary approach in the management of PEAC. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal (GI) cancers represent a significant health burden worldwide. Their incidence continues to increase, and their management remains a clinical challenge. Chimeric antigen receptor (CAR) natural killer (NK) cells have emerged as a promising alternative to CAR-T cells for immunotherapy of GI cancers. Notably, CAR-NK cells offer several advantages, including reduced risk of graft-versus-host disease, lower cytokine release syndrome, and the ability to target cancer cells through both CAR-dependent and natural cytotoxic mechanisms. Main body: This review comprehensively discusses the development and applications of CAR-NK cells in the treatment of GI cancers. We explored various sources of NK cells, CAR design strategies, and the current state of CAR-NK cell therapy for GI cancers, highlighting recent preclinical and clinical trials. Additionally, we addressed existing challenges and propose potential strategies to enhance the efficacy and safety of CAR-NK cell therapy. Conclusions: Our findings highlight the potential of CAR-NK cells to revolutionize GI cancer treatment and pave the way for future clinical applications. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (ZCEA539, ZCEA546, and ZCEA919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled ZCEA affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled ZCEA affibody exhibited high tumortargeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of ZCEA affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

Due to the widespread use of cancer genetic testing in gastrointestinal cancer, the BRCA1/2 genetic mutation has been identified in biliary tract cancer as well as pancreatic cancer. Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, and PARP inhibitors exert their cytotoxicity against cancer cells in the context of homologous recombination deficiency, such as BRCA mutations, via the mechanism of synthetic lethality. The aim of this phase II NIR-B trial is to evaluate the efficacy and safety of niraparib for patients with unresectable advanced or recurrent biliary tract cancer, pancreatic cancer or other gastrointestinal cancers with germline or somatic BRCA1/2 mutations revealed by genetic testing. The primary end point is an investigator-assessed objective response rate in each cohort. Clinical Trial Registration:jRCT2011200023 (ClinicalTrials.gov) Plain Language Summary A clinical study to confirm the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with the BRCA genetic mutation: the NIR-B trial. BRCA gene is involved in repairing DNA injury and plays an important role in cancer growth. Cells with a mutation in the BRCA gene cannot repair DNA using a method called homologous recombination repair. Niraparib is part of a class of drugs called 'PARP inhibitors' that inhibit enzymes called 'PARP' involved in repairing DNA injury, and has shown efficacy against cancers with BRCA gene mutations. BRCA gene mutations are infrequent but have been found in a variety of cancers. The NIR-B trial is a clinical trial to evaluate the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with BRCA gene mutations. Executive summary Background Recent comprehensive genomic profiling testing has revealed therapeutic target molecules. It has been proven that the BRCA1/2 genetic mutation has been identified in biliary tract and pancreatic cancer. Niraparib is classified as a poly(ADP-ribose) polymerase (PARP) inhibitor, and PARP inhibitors exert cytotoxicity against cancer cells in the context of homologous recombination deficiency, such as BRCA mutations, by the mechanism of synthetic lethality. Niraparib has been shown to be selective for PARP1/2 as well as more cytotoxic than other PARP inhibitors owing to its PARP-trapping activity. NIR-B trial This NIR-B trial is a multicenter, open-label, single-arm, three-cohort and basket-type phase II study, with the aim to evaluate the efficacy and safety of niraparib for patients with unresectable advanced or recurrent biliary tract cancer, pancreatic cancer and other gastrointestinal cancers with germline or somatic BRCA1/2 mutations observed on genetic testing. Eligible patients will be enrolled at six trial sites in Japan. Patients with a body weight ≥77 kg and platelet count ≥150,000/mm3 will be administered 300 mg of niraparib orally once daily, while patients with a body weight <77 kg or platelet count <150,000/mm3 will be administered 200 mg of niraparib orally once daily. The primary end point is an investigator-assessed objective response rate (ORR) in each cohort with a threshold ORR of 10% and an expected ORR of 35%. The key secondary end points are progression-free survival, overall survival, disease control rate, duration of response and safety. Pretreatment tumor tissue and serial circulating tumor DNA will be collected and analyzed to investigate the resistance mechanisms and to provide a clinically meaningful biomarker that can be used to identify and implement treatment changes. The trial was initiated in January 2021, and enrollment is ongoing. [ABSTRACT FROM AUTHOR]

Background: Despite remarkable progress in contemporary medical technology and enhanced survival outcomes for various cancer types, pancreatic cancer (PC) continues to stand out as a particularly deadly gastrointestinal malignancy. Given a persistent rise in both incidence and the corresponding mortality rates of PC globally, evaluations of PC burden by sex are of great importance. Here, we used the illness‐death multi‐state model (IDM) to forecast the prevalence of PC through the year 2040. Methods: IDM was established based on obtainable data to predict the future prevalence of PC on global, regional, and national scales from 2019 to 2040. Analyses were also performed regarding sex and 95% confidence intervals (CIs) are presented for all estimates. Results: The projected prevalence rate for 2040 is anticipated to be 6.093 ([95% CI 5.47–6.786] per 100,000) worldwide, indicating a significant increase of 31.45% since 1990, and a 12.29% increase since 2019. The estimated average annual increase since 2020 was 0.5%. Considering sex differences, females are expected to have a steeper slope in prevalence rate than males. Intriguingly, when considering the percentage changes between the periods of 2019–2040 and 1990–2019 for both sexes, females exhibited 29% and 11% increase relative to males (2.6‐fold greater increase). Conclusions: By 2040, it is predicted that the prevalence of PC will increase globally, with women being at higher risk of developing the disease. Considering the percentage changes, regions with lower socioeconomic status are anticipated to face a greater risk of experiencing PC compared to other geographical areas. [ABSTRACT FROM AUTHOR]

Simple Summary: Ochratoxin A (OTA) present in food products poses a serious threat to health due to its wide spectrum of effects, including genotoxicity, nephrotoxicity, neurotoxicity, embryotoxicity, teratogenicity, and immunosuppression. Moreover, it is associated with carcinogenesis, as a result of which it has been classified as a potential human carcinogen. In this review, literature reports on the correlations between carcinogenesis and OTA, with particular emphasis on certain organs such as the kidney or digestive system organs and the cancers associated with them, are gathered. Furthermore, we describe the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations. Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research. [ABSTRACT FROM AUTHOR]

BACKGROUND. Immune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers of irAEs in a diverse pantumor cohort is needed to identify patients at greatest risk and to develop rational treatment and interception strategies. METHODS. In an observational study, we prospectively collected blood samples and performed regular clinical evaluations for irAEs in patients receiving ICI therapy as standard of care for solid tumors. We performed in-parallel analysis of cytokines by Luminex immunoassay and circulating immune cells by cytometry by time-of-flight (CyTOF) at baseline and on treatment to investigate mechanisms of irAEs. RESULTS. We enrolled 111 patients, of whom 40.5% developed a symptomatic irAE (grade ≥ 2). Development of a grade ≥ 2 irAE was positively associated with the use of combination ICI and a history of an autoimmune disorder. Early changes in T helper 17 (Th17) (IL-6, IL-17f), type 2 (IL-5, IL-13, IL-25), and type 1 (TNF-α) cytokine signatures and congruent ontreatment expansions of Th17 and Th2 effector memory (Th2EM) T cell populations in peripheral blood were positively associated with the development of grade ≥2 irAEs. IL-6 levels were also associated with inferior cancer-specific survival and overall survival. CONCLUSIONS. In a diverse, prospective pan-tumor cohort, Th17 and Th2 skewing during early ICI treatment was associated with the development of clinically relevant irAEs but not antitumor responses, providing possible targets for monitoring and therapeutic interventions. FUNDING. Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, the NCI SPORE in Gastrointestinal Cancers (P50 CA062924), NCI grant (R50CA243627 to LD), the NIH Center Core Grant (P30 CA006973), Swim Across America (to MY), NIAMS (K23AR075872 to LC), and imCORE-Genentech grant 137515 (to Johns Hopkins Medicine on behalf of MY). [ABSTRACT FROM AUTHOR]

Background: Intrinsic capacity (IC) was introduced by the World Health Organization (WHO) as a marker of healthy aging, and is defined as the combination of an individual's physical, mental, and psychological capacities. This study aimed to assess IC via a patient‐reported geriatric assessment (GA) and evaluate its association with survival among older adults with gastrointestinal (GI) malignancies. Methods: Data were used from a single‐institution prospective registry of older adults undergoing GA before cancer therapy. Key domains of IC (vitality, locomotion, and sensory [hearing and visual], psychological, and cognitive capacities) were captured via GA, and each was given a score of 0 or 1 (0, impaired) to compute the total IC score (range, 0–6, where 6 indicates no impairment and ≤5 indicates impairment in ≥1 domains). A frailty index (FI) was measured via the deficit accumulation method. Cox regression models and Kaplan–Meier curves were used to examine the impact of IC impairment on survival. Results: The study included 665 patients; the median age was 68 years, 57.4% were men, and 72.9% were White. The median IC score was 4, and 79.3% of participants showed impairment in ≥1 domains of IC. Most commonly impaired domains were locomotion (48.7%) and vitality (43.9%). IC was inversely associated with FI (Spearman coefficient, −0.75; p <.001). IC impairment was associated with inferior overall survival (score, 4–5: adjusted hazard ratio [aHR], 1.7; 95% CI, 1.11–2.48; score, 2–3: aHR, 1.9; 95% CI, 1.30–2.85; score, 0–1: aHR, 1.9; 95% CI, 1.11–2.48). Conclusions: IC impairment is associated with frailty and reduced overall survival in older patients with GI malignancies. GA can be used to screen for IC impairment as recommended by the WHO. Plain Language Summary: The World Health Organization introduced intrinsic capacity as a marker of healthy aging.Intrinsic capacity is the combination of an individual's physical, mental, and psychological capacities. It contains six key domains: vitality, locomotion, and sensory (hearing and visual), psychological, and cognitive capacities.Older adults with cancer are susceptible to a decrease in intrinsic capacity as a result of cancer and the aging process.In this study, we aimed to assess the intrinsic capacity for patients with gastrointestinal cancer and also identify whether there exists any association of intrinsic capacity with overall survival. We identified that approximately 80% of this population had one or more impaired domains, and more intrinsic capacity impairment was associated with reduced overall survival. Geriatric assessment can be used to screen for intrinsic capacity impairment as recommended by the World Health Organization. In older patients with gastrointestinal malignancies, intrinsic capacity impairment is common and associated with frailty and reduced overall survival. [ABSTRACT FROM AUTHOR]

Introduction: Malignancy-related ascites (MRA) is a common serious complication of many advanced malignant tumors with high morbidity and mortality. The high hospital expenditures induced by unplanned readmission in patients with MRA have become an urgent issue to the public. We aimed to overall assess the unplanned early readmission rate of patients with MRA and explore the potential risk factors for such readmission. Methods: A retrospective cohort study based on 2018 Nationwide Readmissions Database was performed and patients with MRA were recruited into the analysis. The primary outcome was unplanned 30-day readmission rate and inpatient outcomes. The multivariate logistic regression analysis was performed to evaluate the potential risk factors for such early readmission. Results: Data obtained from 32,457 patients with MRA were analyzed, and of these 7,799 individuals (24.03%) were unplanned readmitted within 30-day follow-up. The mortality rate in the readmitted population was 15.15%. Patients at younger age were at a higher risk of readmission. The morbidities including hypertension (OR=1.117, 95%CI: 1.054-1.184), hyperlipemia (OR=1.075, 95%CI: 1.009-1.146) and diabetes (OR=1.118, 95%CI: 1.053-1.188), gastrointestinal malignancies and peritoneal procedure significantly increased the risk of 30-day readmission in patients with MRA. Discussion: More than one in five patients with MRA was unplanned readmitted within 30-day follow-up. The above risk factors should be timely intervened and the corresponding medical care should be strengthened in patients with MRA to lessen the unplanned readmission and improve the readmission outcomes. [ABSTRACT FROM AUTHOR]

Background&Aims: Gastrointestinal (GI) cancers, including gastric, liver, esophageal, pancreatic, and colorectal cancers, represent significant global health burdens. Emerging evidence suggests that dietary patterns, particularly their inflammatory and oxidative properties, may influence cancer risk. The Dietary Inflammatory Index (DII) and Dietary Oxidative Balance Score (DOBS) assess the inflammatory and oxidative effects of diets, respectively. This study aims to explore the association between DII, DOBS, and the combined risk of GI cancers, and investigates the potential mediating roles of serum albumin and red cell distribution width (RDW). Methods: Data from 26,320 participants in the NHANES 2005–2018 cycles were analyzed. DII was calculated based on 28 dietary components, and DOBS included 17 nutrients (3 pro-oxidants and 14 antioxidants). Logistic regression models assessed the associations between DII, DOBS, and GI cancers. Restricted cubic spline (RCS) models examined dose-response relationships. Mediation analysis evaluated the roles of serum albumin and RDW. Subgroup analyses explored interactions with demographic and health-related factors. Results: Higher DII was associated with increased GI cancer risk (OR: 1.26, 95% CI: 1.07–1.49 per unit increase), while higher DOBS was associated with reduced risk (OR: 0.90, 95% CI: 0.76–0.99 per unit increase). RCS analysis indicated a significant nonlinear relationship between DII and GI cancer risk. Serum albumin and RDW partially mediated the associations between DII, DOBS, and GI cancers. Subgroup analyses showed stronger associations for DII among certain demographics, and significant interactions were found between DII and BMI. For DOBS, significant interactions were observed with age and BMI. Conclusion: This study reveals significant associations between dietary inflammatory and oxidative balance scores and GI cancer risk. Higher DII is linked to increased risk, while higher DOBS is protective. The mediating roles of serum albumin and RDW provide insights into underlying mechanisms. These findings underscore the potential of dietary modifications in GI cancer prevention and management, emphasizing the importance of anti-inflammatory and antioxidant-rich diets. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Little is known about financial toxicity in early‐phase clinical trial (EP‐CT) participants. This study sought to describe financial toxicity in EP‐CT participants and assess associations with patient characteristics and patient‐reported outcomes (PROs).Prospectively enrolled EP‐CT participants from were followed from April 2021 through January 2023. Participants completed the Comprehensive Score for Financial Toxicity (<26 = financial toxicity) at time of treatment. Quality of life (QOL), symptoms, coping, and resource concerns were surveyed. Associations of financial toxicity with patient characteristics, PROs, and clinical outcomes were explored.Of 261 eligible patients, 197 completed baseline assessments (75.5%, median age = 63.4 years [31.8‐88.6], 57.4% female). Most common cancers were gastrointestinal (33.0%) and breast (20.8%). More than one third (34.0%) of patients reported financial toxicity. Patients with financial toxicity were more likely to be <65 years (70.2% vs 48.5%, p = .004), unemployed (45.5% vs 16.9%, p < .001), not have attended college (53.1% vs 26.4%, p = .002), and have income <$60,000 (59.7% vs 25.4%, p < .001). In adjusted models, patients with financial toxicity reported lower QOL (B = –6.66, p = .004) and acceptance (B = –0.78, p = .002), and increased self‐blame (B = 0.87, p < .001). They were more likely to have concerns regarding housing (10.6% vs 2.3%, p = .025), bills (31.8% vs 3.8%, p < .001), food (9.1% vs 0.8%, p = .006), and employment (21.2% vs 1.5%, p < .001). There was no difference in time on trial (hazard ratio, 1.03; p = .860) or survival (hazard ratio, 1.16; p = .496).More than one third of EP‐CT participants reported financial toxicity. Factors associated with financial toxicity and demonstrated novel associations among financial toxicity with QOL, coping, and resource concerns were identified, highlighting the need to address financial toxicity among this population. [ABSTRACT FROM AUTHOR]

The most common illnesses that adversely influence human health globally are gastrointestinal malignancies. The prevalence of gastrointestinal cancers (GICs) is relatively high, and the majority of patients receive ineffective care since they are discovered at an advanced stage of the disease. A major component of the human body is thought to be the microbiota of the gastrointestinal tract and the genes that make up the microbiome. The gut microbiota includes more than 3000 diverse species and billions of microbes. Each of them has benefits and drawbacks and been demonstrated to alter anticancer medication efficacy. Treatment of GIC with the help of the gut bacteria is effective while changes in the gut microbiome which is linked to resistance immunotherapy or chemotherapy. Despite significant studies and findings in this field, more research on the interactions between microbiota and response to treatment in GIC are needed to help researchers provide more effective therapeutic strategies with fewer treatment complication. In this review, we examine the effect of the human microbiota on anti-cancer management, including chemotherapy, immunotherapy, and radiotherapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a severe gastrointestinal cancer and a leading cause of cancer-related deaths in Ghana. The potential role of gut Enterobacteriaceae in the increasing incidence of CRC in Ghana is yet to be thoroughly investigated. In this study, Enterobacteriaceae from CRC patients and healthy control participants were analyzed by whole genome sequencing to identify genomic features that are associated with CRC. Socio-demographic data showed a significant association between age and alcohol consumption and CRC. Escherichia coli was the most abundant Enterobacteriaceae isolated from the study participants and they were predominantly intestinal commensals. Escherichia coli isolates belonging to phylogroup D encoded the highest number of virulence genes. The agn43 and int genes were widespread in Escherichia coli isolates from the CRC patients. Multilocus sequence types of potentially pathogenic Escherichia coli from the CRC patients also encoded genes involved in aggregation, adherence and biofilm formation. The ampC2 and ampH antimicrobial resistance genes were also widespread in the genome of the Escherichia coli isolates. This study highlights the virulence tendencies of Escherichia coli from CRC patients and their ability to transfer virulence determinants to other Enterobacteriaceae residing in the gut. [ABSTRACT FROM AUTHOR]

The 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Winnipeg, Manitoba, on 26–27 October 2023. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; oncology nurses; pharmacists; and a family physician in oncology (FPO) participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastroesophageal cancers. [ABSTRACT FROM AUTHOR]

The gut microbiota's pivotal role in human health is increasingly evident, particularly in chronic conditions like obesity, diabetes, and inflammatory diseases. This intricate symbiotic relationship influences metabolic balance and immune responses. Notably, gut microbial dysbiosis is linked to obesity's metabolic disruption and chronic low-grade inflammation. Similarly, in diabetes, the microbiota's impact on insulin resistance and glucose metabolism is becoming evident. Chronic inflammation, a common denominator in these conditions, is also a recognized precursor to carcinogenesis. This intersection prompts a compelling question: does the gut microbiota's influence extend to gastrointestinal cancers like colorectal and pancreatic cancer? These malignancies are closely intertwined with inflammation and metabolic dysregulation. Exploring whether the microbial signatures associated with chronic conditions overlap with precancerous or cancerous states offers new perspectives. This article reviews emerging evidence on the interplay between the gut microbiota, chronic conditions, and gastrointestinal cancers. By elucidating these connections, we aim to uncover potential avenues for innovative diagnostic, preventative, and therapeutic strategies in colorectal and pancreatic cancer management. [ABSTRACT FROM AUTHOR]

Background/Objectives: PRKACA alterations have clear diagnostic and biological roles in the fibrolamellar variant of hepatocellular carcinoma and a potential predictive role in that cancer type. However, the roles of PRKACA have not been comprehensively examined in gastric and colorectal cancers (GC and CRC). This study, therefore, sought to investigate the roles of PRKACA expression in GC and CRC. Methods: The clinico-genomic data of 441 GC and 629 CRC cases were analyzed for therapeutic, clinicopathological, and biological correlates using appropriate bioinformatics and statistical tools. Furthermore, the deregulation of PRKACA expression in GC and CRC was investigated using correlative and regression analyses. Results: The results showed that PRKACA expression subsets were enriched for gene targets of chemotherapeutics, tyrosine kinase, and β-adrenergic inhibitors. Moreover, high PRKACA expression was associated with adverse clinicopathological and genomic features of GC and CRC. Gene Ontology Enrichment Analysis also showed that PRKACA-high subsets of the GI cancers were enriched for the biological and molecular functions that are associated with cell motility, invasion, and metastasis but not cell proliferation. Finally, multiple regression analyses identified multiple methylation loci, transcription factors, miRNA species, and PRKACA copy number changes that deregulated PRKACA expression in GC and CRC. Conclusions: This study has identified potential predictive and clinicopathological roles for PRKACA expression in GI cancers and has added to the growing body of knowledge on the deregulation of PRKACA in cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC), a pervasive and lethal malignancy of gastrointestinal cancer, imposes significant challenges due to the occurrence of distant metastasis in advanced stages. Understanding the intricate regulatory mechanisms driving CRC distant metastasis is of paramount importance. CRISPR‐Cas9 screening has emerged as a powerful tool for investigating tumor initiation and progression. However, its application in studying CRC distant metastasis remains largely unexplored. To establish a model that faithfully recapitulates CRC liver metastasis in patients, we developed an in vivo genome‐wide CRISPR‐Cas9 screening approach using a spleen‐injected liver metastasis mouse model. Through comprehensive screening of a whole‐genome sgRNA library, we identified ANKRD42 as a pivotal regulatory gene facilitating CRC liver metastasis. Analysis of the TCGA database and our clinical cohorts unveiled heightened ANKRD42 expression in metastases. At the cellular level, the attenuation of ANKRD42 impaired the migration and invasion processes of tumor cells. In vivo experiments further validated these observations, highlighting the diminished liver metastatic capacity of tumor cells upon ANKRD42 knockdown. To unravel the specific mechanisms by which ANKRD42 regulates CRC distant metastasis, we leveraged patient‐derived organoid (PDO) models. Depleting ANKRD42 in PDOs sourced from liver metastases precipitated the downregulation of pivotal genes linked to epithelial‐mesenchymal transition (EMT), including CDH2 and SNAI2, thereby effectively suppressing tumor metastasis. This study not only establishes a conceptual framework but also identifies potential therapeutic avenues for advanced‐stage distant metastasis in CRC patients. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this research is to propose an intra-operative tumor detection probe calibrated on human models of gastrointestinal (G.I.) cancers, enabling real-time scanning of dissected masses. Methods: Electrical Gastrointestinal Cancer Detection (EGCD) measures impedimetric characteristics of G.I. masses using a handpiece probe and a needle-based head probe. Impedance Phase Slope (IPS) and impedance magnitude (Z1kHz) are extracted as the classification parameters. EGCD was tested on palpable G.I. masses and compared to histopathology results. Results: Calibration was carried out on 120 GI mass samples. Considering pathological results as the gold standard, most cancer masses showed Z1kHz between 100 Ω and 2500 Ω while their IPS was between −15 and −1. The EGCD total sensitivity and specificity of this categorization in G.I. cancer patients with palpable tumors were 86.4% and 74.4%, respectively (p-value < 0.01). Conclusion: EGCD scoring can be used for 3D scanning of palpable tumors in G.I. tumors during surgery, which can help clarify the tumors' pathological response to neoadjuvant chemotherapy or the nature of intra-operative newly found G.I. tumors for the surgeon to manage their surgical procedure better. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer affects millions worldwide, with gastrointestinal cancers being notably common. This review explores the potential of telomeres and telomerase as biomarkers for diagnosing and predicting these cancers. Telomeres are protective caps at chromosome ends that shorten with cell division, while telomerase helps extend them. Changes in these markers could indicate cancer risk and progression. Despite efforts to prevent cancer through lifestyle changes, gastrointestinal cancers such as colorectal and gastric cancer remain prevalent. Current detection methods like endoscopy are invasive, driving interest in non-invasive alternatives. By consolidating research on telomere length and telomerase activity, this review aims to highlight how these biomarkers could enhance early diagnosis and monitoring. Understanding these mechanisms better could lead to improved diagnostic tools and therapeutic strategies, potentially refining how gastrointestinal cancers are managed and improving patient outcomes. Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Bile acid diarrhea (BAD) is an underrecognized and socially debilitating disease caused by high concentrations of bile acids in the colon. Bile acids directly and indirectly promote carcinogenesis. In this article, we investigated whether individuals with BAD have an increased risk of gastrointestinal (GI) cancers. METHODS: By using the Danish health registries, adult individuals with BAD were identified by International Classification of Diseases 10th revision code K90.8 or referral to the diagnostic 75seleniumhomotaurocholic acid test followed by prescription of a bile acid sequestrant within 365 days (n 5 5,245). Age- and sex-matched individuals without BAD were included for comparison (n 5 52,450). We analyzed the cumulative incidence of GI cancers after BAD diagnosis and the odds ratios (ORs) of GI cancer 8 and 15 years before BAD diagnosis/matching. RESULTS: Cumulative incidence of GI cancer 6 years after BAD diagnosis/matching was 1.6% in the BAD group and 1.1% in controls (P50.01). The ORs of total GI cancer 8 and 15 years before BAD diagnosis were 6.16 (5.08-7.48) and 5.19 (4.28-6.29), respectively. Furthermore, 47 individuals with BAD (0.9%) and 250 (0.5%) controls died of GI cancer. DISCUSSION: This nationwide cohort study indicates an association between BAD and GI cancers. We found both a higher incidence of GI cancer after BAD diagnosis compared with controls and increased OR of GI cancer before BAD diagnosis. Bearing in mind the underdiagnosis of BAD, the delay of BAD diagnosis, and the carcinogenic effect of bile acids, these findings warrant further investigations of the risk of GI cancer in individuals with BAD. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a frequent gastrointestinal malignancy with high rates of morbidity and mortality; 85% of these tumours are proficient mismatch repair (pMMR)‐microsatellite instability‐low (MSI‐L)/microsatellite stable (MSS) CRC known as 'cold' tumours that are resistant to immunosuppressive drugs. Monotherapy with programmed death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) inhibitors is ineffective for treating MSS CRC, making immunotherapy for MSS CRC a bottleneck. Recent studies have found that the multi‐pathway regimens combined with PD‐1/PD‐L1 inhibitors can enhance the efficacy of anti‐PD‐1/PD‐L1 in MSS CRC by increasing the number of CD8+ T cells, upregulating PD‐L1 expression and improving the tumour microenvironment. This paper reviews the research progress of PD‐1/PD‐L1 inhibitors in combination with cytotoxic T‐lymphocyte–associated antigen 4 (CTLA‐4) inhibitors, oncolytic virus, intestinal flora, antiangiogenic agents, chemotherapy, radiotherapy and epigenetic drugs for the treatment of pMMR‐MSI‐L/MSS CRC. [ABSTRACT FROM AUTHOR]

A synchronous solid and hematological malignancy is an uncommon condition in which a patient develops two ormore primary cancers, one of which is a solidmalignancy and the other one is a hematological malignancy, within 6 months of primary cancer diagnosis. The most common histology in solid malignancies is gastrointestinal adenocarcinoma, which coexists with the lymphoma subtype diffuse large B-cell lymphoma (DLBCL). Here, we report an extremely rare combination of serous carcinoma of the ovary synchronous with lymphoma of DLBCL subtype. A woman aged 52 years presented with an abdominal mass and abdominal pain for a short duration of 15 days. She was evaluated using clinical, radiological, and biochemical parameters. She was diagnosed with non-Hodgkin lymphoma by tru-cut biopsy from a bony lytic lesion and ovarian cancer by staging laparotomy. R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone) chemotherapy for lymphoma and staging laparotomy for persistent adnexal mass resulted in complete remission of both ovarian cancer and lymphoma. She received paclitaxel and carboplatin-based postoperative chemotherapy as an adjuvant for ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging. Methods: [68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings. Results: Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01). Conclusion: A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent. Clinical trial registration: This study was registered on the ClinicalTrials.gov (NCT05937919). [ABSTRACT FROM AUTHOR]

Background This study aimed to compare colorectal cancer (CRC) awareness between screening-eligible and ineligible individuals in Palestine. Methods Convenience sampling was utilized to recruit Palestinian adults from diverse settings, including hospitals, primary healthcare centers and public spaces across 11 governorates. The evaluation of CRC awareness in terms of signs/symptoms, risk factors and causation myths was conducted using Arabic-translated, modified versions of the validated instruments, the Bowel Cancer Awareness Measure and the Cancer Awareness Measure-Mythical Causes Scale. Results The final analysis included 2698 participants, with 2158 (80.9%) eligible for CRC screening and 540 (19.1%) ineligible for it. The most recognized CRC sign/symptom was 'lump in the abdomen' in both screening-eligible (n = 386, 71.5%) and ineligible (n = 1582, 73.3%) groups. 'Lack of physical activity' was the most recognized risk factor in both groups (eligible: n = 451, 83.5%; ineligible: n = 1766, 81.8%). The most reported causation myth in both groups was 'having a physical trauma' (eligible: n = 340, 63.0%; ineligible: n = 1353, 62.7%). In the screening-eligible group, only 210 participants (38.9%) demonstrated high awareness of CRC signs/symptoms, 213 participants (39.4%) showed high awareness of CRC risk factors and only 46 participants (8.5%) displayed high awareness of CRC causation myths. There were no significant associations between being eligible for screening colonoscopy and the awareness levels of CRC signs/symptoms, risk factors and causation myths. Conclusion Overall, awareness levels of CRC signs/symptoms, risk factors and causation myths were notably low among screening-eligible participants. There were no differences in awareness levels between individuals eligible for colonoscopy and those who were not. [ABSTRACT FROM AUTHOR]

Background: The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population. Methods: Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year. Results: A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1 cm, 1–3 cm, and ≥ 3 cm, respectively. During a median follow-up of 80 months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066–0.013)%/year for BE < 1 cm, 0.026 (0.011–0.054)%/year for 1–3 cm, and 0.58 (0.042–2.11)%/year for ≥ 3 cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031–0.049)%/year and 0.16 (0.14–0.18)%/year, respectively. Conclusions: By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE. [ABSTRACT FROM AUTHOR]

Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P < 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE. This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity. [ABSTRACT FROM AUTHOR]