The U-ACTIVATE long-term extension study aims to evaluate the long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis. Here, we report interim results after 3 years of total treatment.

U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study done at 307 centres across 43 countries (active sites on Dec 31, 2021, are presented as part of this interim analysis) and began on Jan 31, 2017. In brief, patients aged 16-75 years with a confirmed diagnosis of moderately to severely active ulcerative colitis for 90 days or more, an adapted Mayo score of 5-9, and an endoscopic subscore of 2 or 3 were eligible for the upadacitinib induction studies; patients who had a clinical response in the induction studies were eligible to enter the U-ACHIEVE maintenance study. Individuals who completed the U-ACHIEVE maintenance study were subsequently eligible for inclusion in the efficacy population of this long-term extension study. Patients in clinical remission per adapted Mayo score at week 52 of the maintenance study could continue their double-masked treatment upon entering the long-term extension study. Patients not in clinical remission originally randomly assigned to upadacitinib 15 mg were eligible to escalate to upadacitinib 30 mg, those originally randomly assigned to upadacitinib 30 mg continued on upadacitinib 30 mg, and those originally assigned to placebo were eligible to escalate to upadacitinib 15 mg in a masked way. We present data from weeks 48 and 96 of the long-term extension period. Key efficacy outcomes were clinical remission (per adapted Mayo score), endoscopic remission, maintenance of clinical remission, and maintenance of endoscopic remission, and are presented for those patients who had a clinical response after 8 weeks of upadacitinib 45 mg induction, completed 52 weeks of maintenance (U-ACHIEVE maintenance), and subsequently entered the long-term extension. Safety outcomes were treatment-emergent adverse events and adverse events of special interest, which were prespecified and were recorded in two populations: one comprising patients who received at least one dose of study drug in the long-term extension study and the other comprising all patients in the maintenance or long-term extension studies. Our primary approach for efficacy analysis was as-observed (ie, all observed data were used without imputation for missing data until patients switched to a different dose during the long-term extension study). This study is registered with ClinicalTrials.gov (NCT03006068).

414 patients from the phase 3 upadacitinib U-ACHIEVE maintenance study were eligible to enter this long-term extension study for assessment of efficacy endpoints following treatment with upadacitinib. Of these individuals, 369 patients (231 [63%] male individuals and 138 [37%] female individuals) were treated with upadacitinib in the long-term extension study: 142 patients with upadacitinib 15 mg and 227 with upadacitinib 30 mg. In the as-observed population, 84 (71%) of 118 patients receiving upadacitinib 15 mg were in clinical remission at week 48, as were 130 (67%) of 193 receiving upadacitinib 30 mg; by week 96, 69 (76%) of 91 patients receiving upadacitinib 15 mg and 104 (74%) of 141 of those receiving upadacitinib 30 mg were in clinical remission. Most patients who entered the long-term extension in clinical remission maintained it in the as-observed analysis (week 48 upadacitinib 15 mg 62 [81%] of 77 and upadacitinib 30 mg 90 [81%] of 111; week 96 upadacitinib 15 mg 50 [78%] of 64 and upadacitinib 30 mg 69 [84%] of 82). In the as-observed population, 60 (49%) of 123 patients receiving upadacitinib 15 mg and 93 (46%) of 202 receiving upadacitinib 30 mg were in endoscopic remission at week 48; by week 96, 45 (47%) of 95 patients receiving upadacitinib 15 mg and 69 (45%) of 153 receiving upadacitinib 30 mg were in endoscopic remission. Most patients who entered the long-term extension in endoscopic remission maintained it in the as-observed analysis (week 48 upadacitinib 15 mg 28 [70%] of 40 and upadacitinib 30 mg 51 [76%] of 67; week 96 upadacitinib 15 mg 20 [65%] of 31 and upadacitinib 30 mg 37 [73%] of 51). In the long-term extension-only safety analysis, we assessed data from 467 patients, representing 1027·9 patient-years of continuous long-term extension exposure on a consistent upadacitinib dose. Treatment-emergent adverse events were recorded at 238·5 events per 100 patient-years for upadacitinib 15 mg and 233·4 events per 100 patient-years for upadacitinib 30 mg. Event rates of serious treatment-emergent adverse events were 11·7 events per 100 patient-years for upadacitinib 15 mg and 12·4 events per 100 patient-years for upadacitinib 30 mg. The most common adverse events of special interest were hepatic disorder, lymphopenia, creatine phosphokinase elevation, serious infection, neutropenia, and herpes zoster. Three treatment-emergent adverse events leading to death were reported in the long-term extension-only safety population.

This interim analysis supports the positive long-term risk-benefit profile for upadacitinib 15 mg and 30 mg among patients with moderately to severely active ulcerative colitis.

AbbVie.

Colitis-associated colorectal cancer (CAC), which stems from inflammatory bowel disease (IBD), exhibits a high mortality rate. Chronic inflammation can drive the development of colorectal cancer via diverse mechanisms; however, proteomic-level studies in this regard are currently scarce. The chemical drugs conventionally employed for treating IBD carry significant side effects, accentuating the exigency for novel therapeutic agents. We focused on carvacrol, a traditional Chinese medicine-derived monoterpene phenol with anti-inflammatory and antioxidant traits, though its role in colitis and CAC was unclear. Employing TMT-based proteomics, we identified the oxidative stress pathway as crucial in CAC, with ALB, ADAM10, and APCDD1 (hub genes) being vital. Using DSS and AOM/DSS mouse models, carvacrol significantly restored colonic length (p < 0.01) and re-established key tight junction proteins like ZO-1. It also downregulated mRNA levels of inflammatory mediators such as iNOS and IL-6. Moreover, 16S rRNA sequencing and fluorescence in situ hybridization (FISH) assays indicated that the potential mechanism might be ascribed to carvacrol's modulation of the abundance of specific microbiota, such as Lactobacillus, Escherichia coli/Shigella, and Lachnoclostridium. In subsequent investigations, we ascertained that carvacrol exerted remarkable efficacy in the AOM/DSS models, as it markedly reduced the number of colonic tumors (p < 0.05) and concurrently suppressed the disease activity index scores (p < 0.05). These results jointly suggest its prospective role in thwarting the progression of colitis-associated colorectal cancer. Collectively, our study substantiates that carvacrol efficiently safeguards the mucosal barrier and curbs tumorigenesis, potentially via the modulation of gut microbiota.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. The specific cause of UC is still not fully understood, but this condition is believed to arise from a combination of environmental, genetic, microbial, and immune factors. This study aimed to explore the specific roles of macrophages and fibroblasts in UC pathogenesis, focusing on their interactions and contributions to disease progression.

We utilized single-cell RNA sequencing (scRNA-seq) to analyze macrophages and fibroblasts in peripheral blood and colon biopsy samples from UC patients. Bulk RNA sequencing and spatial transcriptomic data from the Gene Expression Omnibus (GEO) database and flow cytometry and multiplex immunohistochemistry (mIHC) data were used for validation. Statistical analyses were performed to assess the correlation between cell abundance and disease severity.

Macrophages and fibroblasts were identified as key communication hubs in UC; specifically, SPP1 + macrophages and CHI3L1 + fibroblasts were significantly enriched at the sites of inflammation. These cells are strongly correlated with disease severity and orchestrate inflammatory responses within the intestinal immune microenvironment, contributing to UC-associated colorectal cancer.

Our study identified SPP1 + macrophages and CHI3L1 + fibroblasts as key contributors to UC pathogenesis. These cells are enriched in inflammatory sites, are correlated with disease severity, and play a role in UC-associated colorectal cancer, providing new insights into UC mechanisms.

There is a need for diagnostic and prognostic biosignatures to improve long-term outcomes in inflammatory bowel disease (IBD). Here, we describe the establishment of the Swedish Inception Cohort in IBD (SIC-IBD) and demonstrate its potential for the identification of such signatures.

Patients aged ≥18 years with gastrointestinal symptoms who were referred to the gastroenterology unit due to suspected IBD at eight Swedish hospitals between November 2011 and March 2021 were eligible for inclusion.

In total, 367 patients with IBD (Crohn's disease, n=142; ulcerative colitis, n=201; IBD-unclassified, n=24) and 168 symptomatic controls were included. In addition, 59 healthy controls without gastrointestinal symptoms were recruited as a second control group. Biospecimens and clinical data were collected at inclusion and in patients with IBD also during follow-up to 10 years. Levels of faecal calprotectin and high-sensitivity C-reactive protein were higher in patients with IBD compared with symptomatic controls and healthy controls. Preliminary results highlight the potential of serum protein signatures and autoantibodies, as well as results from faecal markers, to differentiate between IBD and symptomatic controls in the cohort. During the first year of follow-up, 37% (53/142) of the patients with Crohn's disease, 24% (48/201) with ulcerative colitis and 4% (1/24) with IBD-U experienced an aggressive disease course.

We have established an inception cohort enabling ongoing initiatives to collect and generate clinical data and multi-omics datasets. The cohort will allow analyses for translation into candidate biosignatures to support clinical decision-making in IBD. Additionally, the data will provide insights into mechanisms of disease pathogenesis.

Patients with inflammatory bowel disease (IBD) remain at increased risk for colorectal cancer and death from colorectal cancer compared with the general population despite improvements in inflammation control with advanced therapies, colonoscopic surveillance and reductions in environmental risk factors. This guideline update from 2010 for colorectal surveillance of patients over 16 years with colonic inflammatory bowel disease was developed by stakeholders representing UK physicians, endoscopists, surgeons, specialist nurses and patients with GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodological support.An a priori protocol was published describing the approach to three levels of statement: GRADE recommendations, good practice statements or expert opinion statements. A systematic review of 7599 publications, with appraisal and GRADE analysis of trials and network meta-analysis, where appropriate, was performed. Risk thresholding guided GRADE judgements.We made 73 statements for the delivery of an IBD colorectal surveillance service, including outcome standards for service and endoscopist audit, and the importance of shared decision-making with patients.Core areas include: risk of colorectal cancer, IBD-related post-colonoscopy colorectal cancer; service organisation and supporting patient concordance; starting and stopping surveillance, who should or should not receive surveillance; risk stratification, including web-based multivariate risk calculation of surveillance intervals; colonoscopic modalities, bowel preparation, biomarkers and artificial intelligence aided detection; chemoprevention; the role of non-conventional dysplasia, serrated lesions and non-targeted biopsies; management of dysplasia, both endoscopic and surgical, and the structure and role of the multidisciplinary team in IBD dysplasia management; training in IBD colonoscopic surveillance, sustainability (green endoscopy), cost-effectiveness and patient experience. Sixteen research priorities are suggested.

Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, established as a risk factor for colorectal cancer (CRC) development. Long-standing inflammation appears to play a central role in colitis-associated colorectal cancer (CAC). However, the molecular mechanism underlying CAC progression is still elusive. Previous evidence showed that levels of branched glycosylation regulate T-cell-mediated immune response associated with IBD severity. Here, we revealed that colonic T cells from IBD patients are dynamically regulated by branched N-glycosylation and associated with the risk of CAC development.

We performed in silico analysis for glycome and immune profile of a publicly available human dataset of CAC patients. Additionally, in a well-characterized cohort of CAC patients, we evaluated the N-glycosylation profile of infiltrated colonic immune cells at different stages of carcinogenesis (colitis, dysplasia and cancer). In vivo studies were conducted in Mgat5 KO mice, using AOM/DSS model to induce CAC. Tumor development and colonic T cells glycoprofile were characterized during CAC development.

The combined analysis of human IBD and CAC clinical samples, together with glycoengineered mouse model susceptible to CAC, revealed a gradual and dynamic increase of branched N-glycans in T cells from colitis to dysplasia and cancer. This glycosylation switch was shown to impose inhibitory properties in T cells, precluding an effective antitumor immune response. Mechanistically, we demonstrated that the deletion of branched N-glycans in Mgat5 knockout mice led to CAC suppression due to increased infiltration of CD8+and γδ T cells, contributing to an effective antitumor immune response. From the clinical standpoint, we demonstrated that branched N-glycosylation levels detected in inflamed lesions from IBD patients predicted CAC progression with a sensitivity of 83.3% and specificity of 67.9% when assessed together with age at diagnosis.

Overall, we here disclosed a new mechanism underlying CAC development, identifying a potential clinical biomarker plausible to improve the efficacy of cancer surveillance programs through the early identification of high-risk IBD patients, for preventive clinical and therapeutic strategies.

Flavonoids are a group of polyphenolic compounds distributed in vegetables, fruits and other plants, which have considerable antioxidant, anti‑tumor and anti‑inflammatory activities. Several types of gastrointestinal (GI) cancer are the most common malignant tumors in the world. A large number of studies have shown that flavonoids have inhibitory effects on cancer, and they are recognized as a class of potential anti‑tumor drugs. Therefore, the present review investigated the molecular mechanisms of flavonoids in the treatment of different types of GI cancer and summarized the drug delivery systems commonly used to improve their bioavailability. First, the classification of flavonoids and the therapeutic effects of various flavonoids on human diseases were briefly introduced. Then, to clarify the mechanism of action of flavonoids on different types of GI cancer in the human body, the metabolic process of flavonoids in the human body and the associated signaling pathways causing five common types of GI cancer were discussed, as well as the corresponding therapeutic targets of flavonoids. Finally, in clinical settings, flavonoids have poor water solubility, low permeability and inferior stability, which lead to low absorption efficiency in vivo. Therefore, the three most widely used drug delivery systems were summarized. Suggestions for improving the bioavailability of flavonoids and the focus of the next stage of research were also put forward.

Chronic inflammatory bowel diseases (IBD), such as Crohn's disease (MC) and ulcerative colitis (CU), are serious immune-mediated diseases that affect the gastrointestinal tract and represent a considerable burden for patients. In recent decades, the treatment of IBD has shifted from symptomatic control to more precise, long-term goals. Advances in IBD research have led to therapy goals having been redefined and expanded in order to achieve complete inflammation control and prevent complications in the long term.An important component of modern therapeutic approaches is the definition of specific markers that serve as indicators for the achievement of these therapeutic goals. These markers enable objective monitoring of the success of treatment and thus offer a clear approach for controlling the therapy. The present article focuses on the new therapeutic goals in IBD treatment and discusses the role of therapeutic target markers in clinical practice.A central goal in modern IBD therapy is endoscopic healing, i.e. the complete macroscopic healing of the intestinal mucosa. In clinical practice this includes in particular an ulcer-free mucosa. In contrast to clinical remission alone, endoscopic healing provides an objective assessment of the inflammatory state and correlates strongly with an improved long-term prognosis.The histologic remission goes beyond endoscopic healing and aims to endoscopic healing to no longer detect signs of inflammation at the microscopic level. This is particularly relevant as the results show that patients who achieve a complete histological remission have an even lower recurrence rate and better long-term results than those who only achieve a clinical or endoscopic remission.Even though no curative therapy for IBD currently exists, the complete cure remains the ultimate goal of research. In current practice, this goal is still unattainable in current practice, but progress in genetic and immunological research offers hope. In the long term, the aim is to innovative approaches such as gene editing or immunotherapy to cure the disease. This could mean that patients are not only free of symptoms, but also freed from the burden of the disease in the long term.

In many tumors, the tumor suppressor TP53 is not mutated, but functionally inactivated. However, mechanisms underlying p53 functional inactivation remain poorly understood. SETD8 is the sole enzyme known to mono-methylate p53 on lysine 382 (p53K382me1), resulting in the inhibition of its pro-apoptotic and growth-arresting functions.

We analyzed SETD8 and p53K382me1 expression in clinical colorectal cancer (CRC) and inflammatory bowel disease (IBD) samples. Histopathological examinations, RNA sequencing, ChIP assay and preclinical in vivo CRC models, were used to assess the functional role of p53 inactivation in tumor cells and immune cell infiltration.

By integrating bulk RNAseq and scRNAseq approaches in CRC patients, SETD8-mediated p53 regulation resulted the most significantly enriched pathway. p53K382me1 expression was confined to colorectal cancer stem cells (CR-CSCs) and C1Q+ TPP1+ tumor-associated macrophages (TAMs) in CRC patient tissues, with high levels predicting decreased survival probability. TAMs promote p53 functional inactivation in CR-CSCs through IL-6 and MCP-1 secretion and increased levels of CEBPD, which directly binds SETD8 promoter thus enhancing its transcription. The direct binding of C1Q present on macrophages and C1Q receptor (C1QR) present on cancer stem cells mediates the cross-talk between the two cell compartments. As monotherapy, SETD8 genetic and pharmacological (UNC0379) inhibition affects the tumor growth and metastasis formation in CRC mouse avatars, with enhanced effects observed when combined with IL-6 receptor targeting.

These findings suggest that p53K382me1 may be an early step in tumor initiation, especially in inflammation-induced CRC, and could serve as a functional biomarker and therapeutic target in adjuvant setting for advanced CRCs.

Obesity is positively associated with colorectal cancer (CRC) risk. Diet not only contributes to obesity, but also strongly influences the gut microbiota, a factor that is thought to independently affect CRC. To isolate the role of obesity-associated gut microbiota in CRC and to assess the impact of diet composition on this relationship, we transplanted the gut microbiota from donor mice that developed obesity or remained lean on a high-fat diet (HFD), Western diet (WD), or low-fat diet (LFD) into antibiotic-treated recipient mice that subsequently received azoxymethane to induce CRC. We hypothesized that the obesogenic diets of the donor mice, rather than their obesity status, would be a stronger driver of gut microbiota-mediated CRC development. Interestingly, while evidence supporting our hypothesis was observed, differential effects on CRC outcomes based on the type of obesogenic diets were found, such that HFD-associated gut microbiota promotes tumor incidence whereas WD-associated gut microbiota promotes tumor growth. Significantly enriched bacterial taxa present before tumor induction may be mediating these results through intestinal permeability or inflammation, such as Sutterella and Dorea in mice received HFD-associated gut microbiota, and Bacteroidetes in mice received WD-microbiota. Overall, our results demonstrated that diet drives the gut microbiota-derived impact on CRC development.

It remains unclear if the increased colorectal neoplasia detection rate in inflammatory bowel disease (IBD) by high-definition (HD) dye-based chromoendoscopy compared with HD white-light endoscopy is due to enhanced contrast or increased inspection times. Longer withdrawal times may yield similar neoplasia detection rates as found by HD chromoendoscopy.

To compare colorectal neoplasia detection rates for HD white-light endoscopy with segmental re-inspection and HD chromoendoscopy, using single-pass HD white-light endoscopy as an additional control group.

In a multicentre, randomised controlled trial, IBD patients aged ≥18 years without active disease and scheduled for endoscopic surveillance were included. Patients were 2:2:1 randomised to HD white-light endoscopy with segmental re-inspection of each colonic segment (double pass), HD chromoendoscopy or single-pass HD white-light endoscopy. The primary outcome was colorectal neoplasia detection rate. Assuming equal colorectal neoplasia rates (non-inferiority margin of 10%) between segmental re-inspection and chromoendoscopy and superiority of segmental re-inspection vs single-pass HD white-light endoscopy, a sample size of 566 patients was required.

In total, 563 patients were analysed per-protocol. Colorectal neoplasia detection rates were 10.3% (n=24/234) for HD white-light endoscopy with segmental re-inspection and 13.1% (n=28/214) for HD chromoendoscopy. This confirmed non-inferiority to HD chromoendoscopy (Δ-2.8%, lower limit 95% CI -7.8, p<0.01). In addition, the number of detected colorectal neoplasia per 10 min of withdrawal time was similar between HD white-light endoscopy with segmental re-inspection and HD chromoendoscopy (0.062 vs 0.058, p=0.83). Single-pass HD white-light endoscopy yielded a lower colorectal neoplasia rate (6.1%; n=7/115) than segmental re-inspection but this was not statistically significant (Δ4.1%, 95% CI -2.2:9.6%, p=0.19).

HD white-light endoscopy with segmental re-inspection was non-inferior to HD chromoendoscopy for colorectal neoplasia detection in IBD patients. It can therefore be assumed that the benefit of HD chromoendoscopy may be explained by the longer withdrawal time and not necessarily the enhanced contrast. However, re-inspection per se did not lead to a significantly higher colorectal neoplasia rate than single-pass HD white-light endoscopy alone.

Glycyrrhiza, a legume native to the Mediterranean region, has a long history of ethnomedicinal use in China. Due to its antiviral, antibacterial, anti-inflammatory, antioxidant, antitumor, anti-ulcer, and hepatoprotective properties, Glycyrrhiza is widely utilized in the treatment of gastrointestinal disorders.

The specific mechanisms of the main active constituents of glycyrrhiza in the treatment of inflammatory bowel disease, precancerous lesions and colorectal cancer at all stages of the colitis-associated colon cancer "Inflammation-Dysplasia-Cancer" sequence, as well as its pharmacokinetics, toxicology, formulation improvements, and application studies, are reviewed to provide new insights and perspectives on glycyrrhiza as a dietary supplement to treat and prevent colitis-associated colon cancer.

Information on Glycyrrhiza was retrieved from electronic databases, including PubMed and Web of Science.

Glycyrrhiza is a well-established medicinal plant with significant potential for applications in both the food and pharmaceutical industries. Over 400 active constituents have been identified in Glycyrrhiza, including terpenoids, flavonoids, isoflavones, coumarins, and polyphenols. Numerous studies have demonstrated that Glycyrrhiza and its active compounds can inhibit the "Inflammation-Dysplasia-Cancer" progression of colitis-associated colon cancer by mitigating inflammatory bowel disease, reducing the number of intestinal precancerous lesions, and counteracting colorectal cancer. Furthermore, derivatives and nanocarriers are crucial for the effective treatment of colitis-associated colon cancer using Glycyrrhiza and its active constituents.

In conclusion, Glycyrrhiza is a plant with both medicinal and nutritional value, making it a potential food ingredient and dietary supplement for the treatment of colitis-associated colon cancer.

We aimed to identify changes in surgical indications in patients with ulcerative colitis (UC) in the biologics era in a single tertiary center.

In this retrospective observational study, 108 patients with UC who underwent abdominal surgery for UC at Seoul National University Hospital from 2000 to 2021 were included. We compared the total number of patients undergoing UC before and after the introduction of biologic therapy.

Of the 108 patients with UC (male, 59 and female, 49; mean age, 46.8 years), 30 (27.8%) underwent surgery for neoplasms and 78 (72.2%) for medical intractability without neoplasms. The duration between diagnosis and surgery varied significantly (126.00 months vs. 60.50 months, P = 0.001). A significant difference was also noted in the surgical indications according to time (P = 0.02). Between 2000 and 2010, 12 patients (19.4%) underwent surgery for UC with neoplasms and 50 (80.6%) for UC without neoplasms, while between 2011 and 2021, 18 (39.1%) and 28 patients (60.9%) underwent surgery for UC with and without neoplasms, respectively.

Since 2011, when biological agents were covered by insurance in South Korea, there has been a relative increase in the incidence of surgical indications for neoplasia cases. Focusing on closely monitoring individuals with long-term UC for neoplasms is necessary.

Novel colorectal cancer endoscopic surveillance techniques for inflammatory bowel disease (IBD) have recently been developed.

Compare the efficacy of currently available techniques for dysplasia detection in colonic IBD.

We conducted a systematic literature search from inception to March 2024 for randomized controlled trials (RCTs) or prospective cohort studies enrolling adults with IBD and having surveillance colonoscopy for dysplasia screening. Primary outcome was the number of dysplastic lesions (per-lesion analysis). Secondary outcome was the number of patients with dysplasia (per-patient analysis). We assessed endpoints using the frequentist NMA random effect model.

We included 25 studies (22 RCTs). 4837 patients met eligibility criteria (850 total dysplastic lesions; 105 with advanced dysplasia). Nine different screening techniques were studied. In per-lesion analysis, dye-based chromoendoscopy (DCE) ranked the highest (83%) per SUCRA ranking. DCE was superior to HD-WLE (OR, 1.78; 95% CI, 1.06-3.00). There were no significant differences between NBI and DCE, HD-WLE with SR or CEM in head-to-head comparisons. In a sub-analysis confined to ulcerative colitis (UC), DCE ranked highest (98%) with per-lesion analysis, and was superior to NBI (OR, 1.69; 95% CI, 1.03-2.77).

HD-WLE-SR, DCE and CEM demonstrated superiority over other techniques for detection of dysplasia in colonic IBD. DCE was superior for dysplasia detection in colonic IBD. DCE was superior to HD-WLE in colonic IBD. DCE was the best technique in UC. Further studies to compare HD-WLE-SR and NBI with DCE are warranted to ascertain performance equivalency and define the optimal surveillance technique.

Patients with inflammatory bowel disease (IBD), including ulcerative colitis and colonic Crohn's disease, are at an increased risk of developing colonic dysplasia and neoplasia. Multiple risk factors have been identified that increase the risk of colonic neoplasia in IBD, including but not limited to underlying disease extent, severity, duration, and concomitant primary sclerosing cholangitis. The overall risk of colonic neoplasia in IBD is decreasing but surveillance is still warranted in patients with high-risk features. In this review, we will discuss the epidemiology, pathogenesis, risk factors, approach to surveillance, and management of colonic neoplasia in IBD.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, significantly increases the risk of colon adenocarcinoma (COAD). Disulfidptosis, a novel form of programmed cell death, has been implicated in various diseases, including UC. This study investigates the expression of disulfidptosis-related genes, particularly CD2AP and MYH10, in UC and COAD. Through analysis of public datasets, we found MYH10 significantly upregulated and CD2AP downregulated in UC compared to healthy controls, with consistent patterns in COAD. Immune infiltration analysis revealed correlations between these genes and specific immune cell types, suggesting their roles in immune modulation. Molecular docking showed strong binding affinities of UC drugs such as budesonide and sulfasalazine with CD2AP and MYH10. Connectivity Map analysis identified additional drug candidates, including simvastatin and mephenytoin, which may be repurposed for UC and COAD therapy. These findings suggest disulfidptosis-related genes as potential biomarkers and therapeutic targets, linking chronic inflammation to cancer progression.

Colorectal cancer (CRC) is a significant global health issue, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Countries with a high Human Development Index (HDI) report the highest incidence rates, driven by dietary and lifestyle factors. In contrast, low-to-middle HDI countries are experiencing rising CRC rates due to urbanization and westernization. Japan exemplifies this shift, with increasing CRC incidence linked to the adoption of westernized diets. Despite advances in screening and treatment, CRC-related mortality remains substantial, with 53,088 deaths reported in Japan.

This review examines global and regional CRC trends, focusing on incidence, mortality, and risk factors such as genetic predispositions, diet, and lifestyle influences. The review highlights the growing burden of CRC in Japan and other regions where dietary changes and urbanization are prevalent. Key findings include the significant impact of processed foods, sugary beverages, obesity, alcohol, and smoking on CRC risk, as well as the protective effects of vitamin D, calcium, and fermented foods. The role of inflammatory bowel disease and diabetes in CRC risk is also discussed. Furthermore, the review emphasizes the importance of public health initiatives, including organized screening programs, in mitigating the CRC burden.

Understanding the interplay between genetic, lifestyle, and environmental factors is crucial for developing effective prevention strategies. Enhancing CRC screening, early detection, and public health interventions can significantly reduce CRC-related mortality. Continued research and collaboration are essential for advancing CRC prevention and improving global health outcomes.

We aimed to evaluate the impact of advanced medical therapies (biologicals and small molecules) on time to colectomy and oncological outcomes in ulcerative colitis (UC).

This cohort study included UC patients who underwent colectomy between 2003 and 2022 at 2 referral centers in Belgium and the Netherlands. Exposure was the use of advanced medical therapies. Primary outcomes were time to colectomy and colorectal cancer (CRC) rate, compared between 4 periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017), and P4 (2018-2022). Secondary outcomes were oncological outcomes, including incidental cancers found unexpectedly in resection specimens or during endoscopic follow-up for medication switch.

Among 716 patients, the usage of advanced therapies increased from 36.8% in P1 to 89.7% in P4 (P < .0001). Median time to colectomy remained comparable (P1: 7.1 years [interquartile ranges (IQR), 2.8-12.9] vs P4: 7.2 years [IQR, 2.7-14.6]; P = not significant). Colectomy and colorectal cancer was diagnosed in 72 (10.1%) patients, with no significant change over time (P = .44). Proportion of CRC was lower in patients treated with advanced therapies (4.7% vs 23.6%, P < .0001) and related to a shorter follow-up (median 6.1 vs 10.3 years, P < .0001). Advanced therapy patients had higher incidental cancer rates (37.5% vs 8.3%, P = .002), which was associated with reduced CRC-related survival (HR for CRC-related death: 3.3, 95% CI 1.17-9.4; P = .02).

Despite increased usage of advanced medical therapies, time to resection and CRC rates have remained unchanged in UC patients undergoing colectomy over the past 2 decades. Advanced therapy patients had higher incidental cancers rates, associated with decreased CRC survival. Awareness of timely colectomy is crucial for this group.

Endoscopic resection of visible dysplastic lesions in patients with inflammatory bowel disease (IBD) is an alternative to colectomy. The endoscopic techniques that can be used include endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and ESD combined with EMR. These endoscopic approaches may allow organ preservation in patients with IBD. This study aimed to evaluate the outcomes of endoscopic resection, including EMR, ESD, and ESD combined with EMR, for the treatment of colorectal dysplasia in patients with IBD.

This was a retrospective review of patients with IBD who underwent endoscopic resection for colorectal dysplasia at our tertiary care center between 2014 and 2023. Patients were identified via a search of our endoscopy database. Medical records were reviewed to collect data on patient demographics, IBD history, details of endoscopic technique, procedural factors, final pathology results, and outcomes, including recurrence of dysplasia.

A total of 50 patients with IBD who underwent endoscopic resection were included in the study, with 38 ESD cases, 11 ESD combined with EMR cases, and 1 EMR case. The median age was 62 years, (IQR, 54-68), and 34 patients (68%) were male. The median body mass index was 27.6 kg/m2 (IQR, 24.8-31.7). The underlying diagnoses were ulcerative colitis in 33 patients (66%) and Crohn's disease in 17 patients (33%). The median disease duration was 27.5 years (IQR, 8-30). Polyp locations were distributed as follows: right colon, rectum, left colon, transverse colon, and cecum, with 9 polyps (18%) in each area. The median procedure time was 47.5 min (IQR, 31.2-73.7). En bloc resection was performed in 34 patients (68%), and piecemeal resection was performed in 16 patients (32%). On pathology, the median lesion size was 23.5 mm (IQR, 20.2-40.0). High-grade dysplasia was found in 7 patients (14%), whereas low-grade dysplasia was found in 15 patients (30%). During a median follow-up period of 3 years, 18% of patients experienced recurrence. No significant difference in recurrence rates was observed between the ESD and ESD combined with EMR groups.

Endoscopic resection, including EMR, ESD, and ESD combined with EMR, is an effective treatment of visible dysplastic lesions and is a safe alternative to colectomy in patients with IBD. In this cohort, favorable short-term outcomes were observed after endoscopic resection.

Dietary fiber influences the composition and metabolic activity of microbial communities, impacting disease development. Current understanding of the intricate fiber-microbe-disease tripartite relationship remains fragmented and elusive, urging a systematic investigation. Here, we focused on microbiota disturbance as a robust index to mitigate various confounding factors and developed the Bio-taxonomic Hierarchy Weighted Aggregation (BHWA) algorithm to integrate multi-taxonomy microbiota disturbance data, thereby illuminating the complex relationships among dietary fiber, microbiota, and disease. By leveraging microbiota disturbance similarities, we (1) classified 32 types of dietary fibers into six functional subgroups, revealing correlations with fiber solubility; (2) established associations among 161 diseases, uncovering shared microbiota disturbance patterns that explain disease co-occurrence (e.g., type II diabetes and kidney diseases) and distinct microbiota patterns that discern symptomatically similar diseases (e.g., inflammatory bowel disease and irritable bowel syndrome); (3) designed a body-site-specific microbiota disturbance scoring scheme, computing a disturbance score (DS) for each disease and highlighting the pronounced capacity of Crohn's disease to disturb gut microbiota (DS = 14.01) in contrast with food allergy's minimal capacity (DS = 0.74); (4) identified 1659 fiber-disease associations, predicting the potential of dietary fiber to modulate specific microbiota changes associated with diseases of interest; (5) established murine models of inflammatory bowel disease to validate the preventive and therapeutic effects of arabinoxylan that notably perturbed the Bacteroidetes and Firmicutes phyla, as well as the Bacteroidetes and Lactobacillus genera, aligning with our model predictions. To enhance data accessibility and facilitate targeted dietary intervention development, we launched an interactive webtool-mDiFiBank at https://mdifibank.org.cn/.

Inflammatory Bowel Disease (IBD) is a persistent ailment that impacts many individuals worldwide. The interaction between the immune system and gut microbiome is thought to influence IBD development. This study aimed to assess some microbiota in IBD patients compared to healthy individuals. The investigation involved a selected group of twenty patients suffering from IBD and an equal number of healthy participants. Stool specimens were obtained and analyzed for Lactobacillus, Bifidobacterium, Bacteroides, Clostridium leptum, Akkermansia muciniphila, Fusobacterium and Enterobacteriaceae using real-time PCR. The findings indicated significantly higher levels of Bifidobacterium in IBD patients (Pv = 0.009) and lower levels of A. muciniphila (Pv = 0.003) healthy individuals. Other bacteria tested did not show significant differences. The study suggests that the progression of IBD patients could be influenced by the rising of Bifidobacterium and the declining of A. muciniphila. Targeting these bacteria could lead to improved treatments and quality of life for those with IBD.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that presents significant challenges in terms of treatment owing to a pronounced likelihood of recurrence and an elevated risk of cancer development, thereby imposing substantial risks on affected individuals. The gut microbiota of Firmicutes and Bacteroidetes (F/B) can affect diseases associated with IBD, which is also a risk factor for breast cancer. This review discusses the hazards associated with UC, highlights the existing disparities in UC-associated gut microbiome research, explores the concept of the F/B ratio and scrutinizes its correlation with UC. Moreover, the differences in the F/B ratios between healthy individuals and those with UC were thoroughly examined. These findings suggest that an elevated F/B ratio may promote the occurrence and progression of UC. Consequently, the F/B ratio may play a significant role in UC by influencing gut microbiota composition and inflammatory responses, suggesting that future research should focus on this ratio as a potential biomarker for disease progression and therapeutic targets in managing UC.

The management of inflammatory bowel disease has seen significant advancements with the introduction of endoscopic examinations, allowing for diagnosis, assessment of inflammation severity, and monitoring of treatment response. The frequency of follow-up endoscopies is personalized based on the factors such as the disease course and treatment response. Endoscopic findings should be well described, and biopsies should be acquired in a thoughtful, protocolized manner. While endoscopy is essential, it has certain limitations. It can be invasive, cause discomfort and associated with possible complications.

The prevalence of colorectal cancer (CRC) in patients with ulcerative colitis (UC) is higher than in the general population, in Latin America there is a progressive increase of UC, and information about CRC screening in inflammatory bowel disease (IBD) is scarce. The aim of this study was to analyze the findings of endoscopic surveillance of CRC in patients with IBD according to available technology.

Multicenter, cross-sectional, analytical study conducted in Latin American countries, in patients with UC, predominantly with more than 8 years of diagnosis and different degrees of disease activity. Surveillance colonoscopies were performed according to available technology. Risk factors for dysplasia detection were analyzed.

One hundred and forty-four patients, 55.5% women, mean age 47.3 (range 17.1 to 90; SD 15.64) years and mean duration of disease 12.71 (range 0.64 to 57.13; SD 8.08) years. Forty-nine lesions were identified, 18 corresponded to dysplasia. The detection rate of dysplasia per lesion and per procedure was 36.7% and 12.5%, respectively. By logistic regression analysis, the duration of disease (OR 1.12;95%CI:1.047 to 1.215, P = .002) and the presence of post-inflammatory polyps (OR 3.4;95%CI:1.11 to 10.36, P = .031) were risk factors for higher detection of dysplasia. Digital chromoendoscopy was associated with greater detection of dysplasia (OR 4.99, 95%CI: 1.092 to 22.864, P = .038).

In our region, the duration of disease and the presence of post-inflammatory polyps were the factors with the highest association for dysplasia detection, and digital chromoendoscopy with directed biopsies was the technique of choice. The implementation of a specific surveillance program in colonoscopy in IBD is an effective strategy to achieve high detection rates.

Patients with inflammatory bowel disease (IBD) face an elevated risk of developing colorectal cancer (CRC). Endoscopic surveillance is a cornerstone in CRC prevention, enabling early detection and intervention. However, despite recent advancements, challenges persist. Chromoendoscopy (CE), considered the gold standard for dysplasia detection, remains underutilized due to logistical constraints, prolonged procedural times, and the need for specialized training. New technologies, such as endomicroscopy, confocal laser endomicroscopy (CLE), and molecular endoscopy (ME), promise unprecedented precision in lesion characterization but are limited to specialized centers. Artificial intelligence (AI) can transform the field; however, barriers to widespread AI adoption include the need for robust datasets, real-time video integration, and seamless incorporation into existing workflows. Beyond technology, patient adherence to surveillance protocols, including bowel preparation and repeat procedures, remains a critical hurdle. This review aims to explore the advancements, ongoing challenges, and future prospects in CRC prevention for IBD patients, focusing on improving outcomes and expanding the implementation of advanced surveillance technologies.

Cancer has become one of the major diseases threatening human health in the twenty-first century due to its incurability. In 2022, new cases of esophageal and gastrointestinal cancers accounted for 17.1% of all newly diagnosed cancer cases worldwide. Despite significant improvements in early cancer screening, clinical diagnostics, and treatments in recent years, the overall prognosis of digestive system cancer patients remains poor. The DEAD-box helicase family, a crucial member of the RNA helicase family, participates in almost every aspect of RNA metabolism, including transcription, splicing, translation, and degradation, and plays a key role in the occurrence and progression of various cancers. This article aims to summarize and discuss the role and potential clinical applications of DEAD-box helicase family proteins in digestive system cancers. The discussion includes the latest progress in the occurrence, development, and treatment of esophageal and gastrointestinal tumors; the main functions of DEAD-box helicase family proteins; their roles in digestive system cancers, including their relationships with clinical factors; effects on cancer proliferation, migration, and invasion; and involved signaling pathways; as well as the existing inhibitory strategies targeting DDX family proteins, are discussed. Additionally, outlooks on future research directions are provided.

This study aimed to investigate the role of a newly isolated strain L.reuteri LY2-2 in colitis in mice and explored the underlying mechanisms. METHODS L.

LY2-2 was orally administered to mice with dextran sulfate sodium (DSS)-induced colitis. 5-Aminosalicylic acid (5-ASA) treatment was used as the drug control.

The results showed that the disease severity of colitis mice was significantly alleviated. The intestinal inflammation was restricted by synergistically reducing pro-inflammatory cytokines, inhibiting TLR4-NF-κB signaling, restoring the abnormal immune response, and enhancing intestinal barrier function. Of note, L.reuteri LY2-2 showed great potential in modulating macrophages polarization in colonic tissues. Moreover, the gut dysbiosis was improved. The potentially pro-inflammatory pathogenic bacteria such as Helicobacter and Romboutsia decreased and the probiotics including L.rhamnosus and L.plantarum increased. Interestingly, the above pathological indexes in the L.reuteri LY2-2 group were better than those in the 5-ASA group.

L.reuteri LY2-2 had a better protective effect on DSS-induced colitis via its anti-inflammatory and microbiota-balancing properties, which supports the potential value of this probiotic against colitis. These results contribute to product development of functional probiotics for colitis and provide valuable insights for their mechanisms of biological function to affect human health status.

UC patients suffer more from colorectal cancer (CRC) than the general population, which increases with disease duration. Early colonoscopy is difficult because ulcerative colitis-associated colorectal cancer (UCAC) lesions are flat and multifocal. Our study aimed to identify promising UCAC biomarkers that are complementary endoscopy strategies in the early stages.

The datasets may be accessed from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The co-expressed modules of UC and CRC were determined via weighted co-expression network analysis (WGCNA). The biological mechanisms of the shared genes were exported for analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To identify protein interactions and hub genes, a protein-protein interaction network and CytoHubba analysis were conducted. To evaluate gene expression, external datasets and experimental validation of human colon tissues were utilized. The diagnostic value of core genes was examined through receiver operating characteristic (ROC) curves. Immune infiltration analysis was employed to investigate the associations between immune cell populations and hub genes.

Three crucial modules were identified from the WGCNA of UC and CRC tissues, and 33 coexpressed genes that were predominantly enriched in the NF-κB pathway were identified. Two biomarkers (CXCL1 and BCL6) were identified via Cytoscape and validated in external datasets and human colon tissues. CRC patients expressed CXCL1 at the highest level, whereas UC and CRC patients showed higher levels than the controls. The UC cohort expressed BCL6 at the highest level, whereas the UC and CRC cohorts expressed it more highly than the controls. The hub genes exhibited significant diagnostic potential (ROC curve > 0.7). The immune infiltration results revealed a correlation among the hub genes and macrophages, neutrophils and B cells.

The findings of our research suggest that BCL6 and CXCL1 could serve as effective biomarkers for UCAC surveillance. Additionally, they demonstrated a robust correlation with immune cell populations within the CRC tumour microenvironment (TME). Our findings provide a valuable insight about diagnosis and therapy of UCAC.

To study digestive system cancer risks in individuals with inflammatory bowel diseases (IBDs) in the biologic era.

We used population-level administrative and cancer registry data from Ontario, Canada, (1994-2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths.

Among 110,919 people with IBD and 1,109,190 controls, colorectal cancer incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change [AAPC] -1.81; 95% confidence interval [CI] -2.48 to -1.156) and controls (AAPC -2.79; 95% CI -3.44 to -2.14), while small bowel cancer incidence rose faster in those with Crohn's disease (AAPC 9.68; 95% CI 2.51-17.3) than controls (AAPC 3.64; 95% CI 1.52-5.80). Extraintestinal digestive cancer incidence rose faster in people with IBD (AAPC 3.27; 95% CI 1.83-4.73) than controls (AAPC -1.87; 95% CI -2.33 to -1.42), particularly for liver (IBD AAPC 8.48; 95% CI 4.11-13.1) and bile duct (IBD AAPC 7.22; 95% CI 3.74-10.8) cancers. Beyond 2010, the incidences (and respective mortality rates) of colorectal (1.60; 95% CI 1.46-1.75), small bowel (4.10; 95% CI 3.37-4.99), bile duct (2.33; 95% CI 1.96-2.77), and pancreatic (1.19; 95% CI 1.00-1.40) cancers were higher in people with IBD.

Cancer incidence is declining for colorectal cancer and rising for other digestive cancers in people with IBD. Incidence and mortality remain higher in people with IBD than controls for colorectal, small bowel, bile duct, and pancreatic cancers.