Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN) can be difficult to treat using traditional endoscopic resection methods. This study evaluated the outcomes of endoscopic submucosal dissection (ESD) in patients with IBD and HR-CANs.

 This retrospective multicenter study consecutively included patients with IBD who were referred to expert Italian endoscopy centers for ESD or hybrid ESD (hESD) of HR-CANs. The main outcomes were rates of en bloc, R0, and curative resections, adverse events, local recurrence, metachronous lesions, and post-resection surgery. Kaplan-Meier method was used to analyze survival rates. Risk factors associated with the main outcomes were investigated by univariable analysis.

 91 patients with colonic IBD (disease duration 15.3 [SD 8.7] years, 82.4 % with ulcerative colitis) with 96 HR-CANs (mean size 34.8 [SD 16.2] mm, 53.1 % high grade dysplasia/adenocarcinoma) were included. ESD and hESD were performed in 82.3 % and 17.7 %, respectively. En bloc, R0, and curative resections were achieved in 95.8 % (95 %CI 89.6-98.8), 85.4 % (95 %CI 76.7-91.7), and 83.3 % (95 %CI 74.3-90.1). Adverse events occurred in 12.5 % (95 %CI 6.6-20.8), which were all conservatively managed. After a mean follow-up of 23.4 (SD 16.1) months, local recurrence and metachronous lesions each occurred in 3.1 %. Post-resection surgery was required in 11.5 %.

 ESD of HR-CANs showed favorable outcomes on the medium- and long-term course in patients with IBD.

Inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) remains a significant clinical challenge due to its link with chronic inflammation and the inherent limitations of current prevention and surveillance strategies. The cGAS-STING pathway has emerged as a key player in the immune regulation of inflammation-driven carcinogenesis, demonstrating both protective and pathogenic roles. This review examines the contrasting roles of the cGAS-STING signaling pathway in intestinal inflammation and colitis-associated cancer (CAC), emphasizing its promise as a target for cancer prevention strategies. Evidence suggests that modulating this pathway could preserve epithelial integrity, limit chronic inflammation, and bolster anti-tumor immunity. Despite advancements in therapies like mesalazine and surveillance colonoscopy programs, gaps in efficacy remain, particularly for Crohn's disease and high-risk populations. Future research should focus on integrating cGAS-STING-targeted approaches with existing modalities to provide personalized and less invasive strategies for CAC prevention. By harnessing this pathway's therapeutic potential, a paradigm shift in managing IBD-associated CRC may be achieved, addressing the challenges of long-term disease surveillance and prevention.

We herein present the case of a 30-year-old Japanese male patient with ulcerative colitis (UC) who was admitted to our hospital because of significant ascites. Upon evaluation, the patient was diagnosed with unresectable UC-associated colon cancer (UCAC), localized in the transverse colon. Using gene profiling of the tumor tissue, anti-epidermal growth factor receptor (EGFR) antibody combination chemotherapy was selected. Subsequently, the patient exhibited a temporary response to this regimen, with an enhancement in his quality of life and he was able to survive for 12 months. This case underscores the potential benefits of aggressive chemotherapy tailored to the gene profile in UCAC treatment, offering insights into potential avenues for improving the patient prognosis.

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.

Background/Objectives: Patients with inflammatory bowel disease (IBD) face an increased risk of developing intestinal and extraintestinal cancers. This retrospective single-center study aimed to quantify cancer risk and identify potential risk factors associated with cancer in IBD patients. Methods: The epidemiological data, disease characteristics, treatment regimens, and occurrences of cancer following IBD diagnosis were collected between January 2021 and February 2022. Hazard ratios (HRs) and standardized incidence ratios (SIRs) were estimated. Results: 560 IBD patients were included; 37 patients developed cancer, with 5 patients developing two distinct cancers, resulting in 42 cancers overall. This translated into a twofold increased risk of developing any cancer compared to the general population (SIR 1.94, 95% CI 1.4-2.6). Colorectal (CRC, 29%), skin (19%), and breast cancer (17%) were the most common malignancies. Female patients showed an increased risk for all cancers (SIR 3.1, 95% CI 2.06-4.3), melanoma (SIR 5.6, 95% CI 1.14-16.2), and CRC (SIR 7.5, 95% CI 3-15.4). Conversely, male patients exhibited a significantly increased risk of lymphoma (SIR 26.2, 95% CI 3.2-95.7). Young age at IBD diagnosis and the use of immunomodulators, whether as monotherapy or in combination with biologics, were associated with an increased risk of cancer. Conclusions: The risk of CRC and lymphoma in IBD patients may be higher than previously reported, potentially due to the increasing use of combination therapy. Cancer risk in IBD should be regularly assessed and personalized throughout the disease course.

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.

Crohn's colitis is an inflammatory bowel disease affecting the colon, which can result in serious complications such as intestinal perforation and peritonitis. Clinically, it presents with symptoms like abdominal pain, diarrhea, and vomiting, which can be misinterpreted or overlooked, leading to diagnostic delays. We present an autopsy case of a 43-year-old woman with no significant past medical history, who initially consulted the Emergency Department for persistent abdominal pain, vomiting, and diarrhea over a 10-day period. Despite symptomatic treatment, no further diagnostic investigations were conducted. Three days later, she presented a sudden loss of consciousness at home and she was declared dead shortly thereafter. A medico-legal autopsy was ordered to determine the cause of death. External examination revealed cyanosis of the face and nails, abdominal distension, and no signs of trauma. At the internal examination, there were a stercoral peritoneal effusion of approximately 400 ml and multiple perforations in the colon, specifically in the ascending colon and sigmoid regions. Further examination showed an inflamed, hemorrhagic colonic mucosa. Histological analysis revealed deep ulcerations and areas of transmural inflammation alternating with healthy mucosa, typical of Crohn's colitis. No other organ abnormalities were noted. Toxicology tests were negative. The cause of death was attributed to peritonitis secondary to colonic perforation due to undiagnosed Crohn's colitis.

Patients with ulcerative colitis are at increased risk for colorectal neoplasia compared to the general population. The risk factors include family history of colorectal cancer, wide extent of colitis, disease duration, cumulative inflammatory burden, and primary sclerosing cholangitis. Here, we report a case of colorectal neoplasia developed in a patient with ulcerative colitis.

The aim of this study was to investigate the impact of Crohn's disease (CD) on patient and cancer characteristics and mortality in patients with colorectal cancer (CRC).

This was a nationwide cohort study of patients diagnosed with CRC in Denmark from 1 January, 2009 to 31 December, 2019. Cancer characteristics were retrieved from the Danish Colorectal Cancer Group registry and merged with a nationwide cohort for inflammatory bowel disease. The main outcome was all-cause mortality in CRC patients with and without CD, comparing CD patients with CRC with those in the general CRC population (non-CD CRC), evaluated by adjusted Cox regression analysis and propensity score matching.

Of 38 077 CRC patients, 245 (0.6%) had CD. The median age at cancer diagnosis was 69 years (interquartile range [IQR]: 60-76) for CD-CRC and 71 years (IQR: 64-78) for non-CD CRC (p < 0.001). Most cancers were located in the right colon in the CD-CRC group. CD was not associated with increased all-cause mortality in the cohort overall. CD patients with colon and rectal cancers and UICC Stage III tumors had a higher mortality rate in both multivariate {hazard ratio (HR) 1.60 (95% confidence interval [95% CI], 1.13-2.27), p = 0.008} and univariate analyses (HR 1.57 [95% CI, 1.11-2.22], p = 0.011). In the propensity score-matched analysis, CD was not associated with increased mortality for colon cancer (HR 1.06 [0.82-1.36], p = 0.7) or rectal cancer (HR 1.25 [0.79-1.98], p = 0.3).

This nationwide study identified distinct features of colon and rectal cancers in patients with CD that have implications for the timing of diagnoses, disease course, and mortality specifically in UICC Stage III disease.

Chronic inflammation of the intestine is a significant risk factor in the development of colorectal cancer. The emergence of colitis and colorectal cancer is a complex, multifactorial process involving chronic inflammation, immune regulation, and tumor microenvironment remodeling. Macrophages represent one of the most prevalent cells in the colorectal cancer microenvironment and play a pivotal role in maintaining intestinal health and the development of colitis-associated colon cancer (CAC). Macrophages are activated mainly in two ways and resulted in three phenotypes: classically activated macrophages (M1), alternatively activated macrophages (M2). The most characteristic of these cells are the pro-inflammatory M1 and anti-inflammatory M2 types, which play different roles at different stages of the disease. During chronic inflammation progresses to cancer, the proportion of M2 macrophages gradually increases. The M2 macrophages secrete cytokines such as IL-10 and TGF-β, which promote angiogenesis and matrix remodeling, and create the favorable conditions for cancer cell proliferation, infiltration, and migration. Therefore, macrophage polarization has a dual effect on the progression of colitis to CAC. The combination of immunotherapy with reprogrammed macrophages and anti-tumor drugs may provide an effective means for enhancing the therapeutic effect. It may represent a promising avenue for developing novel treatments for CAC. In this review, we focus on the process of intestinal macrophage polarization in CAC and the role of intestinal macrophage polarization in the progression of colitis to colon cancer, and review the immunotherapy targets and relevant drugs targeting macrophages in CAC.

There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted.

PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled.

Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%.

The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.

Patients with inflammatory bowel disease (IBD) in the colon have a higher risk for colorectal cancer (CRC). Virtual chromoendoscopy (VCE) allows identification and assessment of colonic dysplasia, which might displace dye-based chromoendoscopy (DCE) as the endoscopist's technique of choice for these patients within endoscopic surveillance programs.

to analyze the best evidence available on the usefulness of VCE versus DCE for dysplasia identification in patients with long-standing colonic IBD.

a qualitative, PRISMA 2020-based systematic review of the literature was carried out in the PubMed, Science Direct, and Scielo databases until June 2023. Clinical trials, case-control studies, comparative studies, and crossover studies in English or Spanish were included that directly compared DCE versus VCE for the screening of colonic dysplasia in patients with IBD. The Quality Assessment of Diagnostic Accuracy studies (QUADAS) 2 was used for assessing study quality. The selected studies were evaluated by 2 independent researchers, who entered their abstracted results into a database.

out of 141 identified studies 9 were selected that compared DCE with VCE (1131 patients included). Six studies are prospective, randomized, controlled trials; 2 are retrospective case-control studies; and 1 is a prospective comparative study. VCE showed a dysplasia detection ability similar to that of DCE, albeit with shorter examination times (8 studies; 985 patients). Factors associated with dysplasia identification included lesions in the right colon (3 studies; 581 patients); non-polypoid lesions (1 study; 210 patients) and/or lesions with Kudo's type III-V pit patterns (2 studies; 254 patients); and patient age (1 study; 129 patients).

VCE may be an alternative to DCE for CRC screening in patients with long-standing IBD, with similar detection ability for colonic dysplasia and the benefit of shorter procedure times. Currently available evidence is limited in this regard given the small numbers of patients in the relevant studies, hence further research is necessary with greater numbers of included subjects.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterised by episodes of symptoms including rectal bleeding, increased stool frequency and abdominal pain, impacting quality of life significantly. Conventional treatments often come with potential side effects and may not be sufficient. Acupuncture is increasingly recognised for its potential benefits in UC. This study aims to assess the efficacy and safety of acupuncture for symptom relief in mild to moderate UC.

This single-centre, parallel-arm, randomised, sham-controlled, the two-step acupuncture (TSA)-UC trial, will involve 64 adults with mild to moderate UC, randomly assigned in a 1:1 ratio to either the acupuncture or sham acupuncture group. Participants will receive 20 sessions of two-step acupuncture or sham acupuncture therapy over 8 weeks. Blinding will be applied to participants, outcome assessors and statisticians. The primary outcome measure is the change in Patient-Reported Outcome 2 (PRO2) from baseline at week 8. Secondary outcomes include changes from baseline in the following scales: PRO2 at other time points, weekly average Numeric Rating Scale (NRS) for bowel urgency, weekly average NRS for abdominal pain (both associated and not associated with bowel movement), the 32-item Inflammatory Bowel Disease Questionnaire, Work Productivity and Activity Impairment Questionnaire-IBD, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. The Patient Global Impression of Change will also be assessed. Long-term effects of acupuncture will be explored. Adverse events and additional treatments will be monitored throughout the study. The modified intention-to-treat population including participants who complete baseline assessments and receive at least one treatment session will be analysed.

The study has received ethical approval from the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (2024-190-KY). The results will be published in a peer-reviewed medical journal.

NCT06615765.

Background: Ceramide 2-aminoethylphosphonate (CAEP), a major sphingolipid class in mollusks, possesses unique structures that are not observed in other sphingolipids. CAEP has a carbon-phosphorus bond and unusual long-chain bases (LCBs). CAEP has been reported to exhibit nutritional functions, such as improving skin conditions and promoting cholesterol metabolism. Objectives: In this study, we investigated the role of dietary CAEP in the formation of aberrant crypt foci (ACF) and colon inflammation induced by 1,2-dimethylhydrazine (DMH) in mice. Methods: Five-week-old female Bagg Albino/c mice were divided into four groups (n = 11), which were treated with the respective experimental diet and DMH intraperitoneal injection nine times for ten weeks. The results obtained after administering CAEP were compared with those obtained after administering sphingomyelin (SPM), which is a major sphingolipid in mammal-derived foods. Results: The predominant LCB in the octopus-extracted CAEP was determined as hexadeca-4-sphingenine. Dietary CAEP suppressed the formation of ACF, and egg yolk-derived dietary SPM exerted a higher suppressive effect on the formation of ACF. Additionally, dietary CAEP suppressed the DMH-decreased expressions of two inflammation-related cytokines in the colon mucosa, whereas dietary SPM normalized the expressions of two cytokines different from those suppressed by CAEP. Conclusions: CAEP provides intestinal protection, with effects that differ from those of SPM. The polar head groups or LCBs in sphingolipids are important for determining their nutritional function in the intestine. The study findings contribute toward the understanding of the nutritional benefits of sphingolipids in daily diets or supplements in maintaining intestinal health.

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.

Background/Objectives: Inflammatory bowel diseases (IBDs) are chronic intestinal disorders with an unpredictable course. In parallel with the advent of new biologic therapies targeting specific interleukin pathways, end-point targets have become more stringent, aiming for mucosal and even histologic healing. Methods: We conducted a prospective study assessing immunohistochemical (IHC) parameters in 46 IBD patients treated with biologic therapy. A similar IHC analysis was performed for comparison with a cohort of 10 "non-IBD" patients. Results: The highest integrated optical density (IOD) of TNF-α was observed in patients with dysplasia, abscesses, mucin depletion and basal plasmacytosis. Non-responders had higher pre- and post-treatment TNF-α expression in both UC and CD compared to responders. On the contrary, the same analysis conducted in the subpopulation treated with anti-TNF-α therapy (Infliximab and Adalimumab) did not reveal a substantial difference in TNF-α expression between responders and non-responders. High pre-treatment interleukin-10 expression was associated with biologic therapy failure, histological inflammatory activity and longer disease duration. Conclusions: Pre-treatment assessment of IL-10 might be a useful tool for identifying a high-risk subset of IBD patients and determining a more aggressive therapy and intensive monitoring strategy.

Inflammatory bowel diseases (IBD) represent chronic inflammatory multisystemic disorders that primarily involve the gastrointestinal tract. Patients with ulcerative colitis (UC) and Crohn's disease (CD) exhibit a higher prevalence of thyroid disorders compared to the general population. The aim of this review is to summarize the literature on concomitant IBD and thyroid disorders, specifically autoimmune thyroid diseases such as Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as thyroid cancer, with a focus on children and adolescents. We provide an overview of the age-related differences between children and adults in the prevalence of this association. Literature shows that relatively few studies have been conducted on this subject in pediatric populations. The etiopathogenetic similarities between IBD and autoimmune thyroiditis are undeniable. Nevertheless, current data does not indicate a unanimous association between GD and HT and chronic IBD (both CD and UC). Although evidence suggests a potential association between IBD and thyroid cancer, particularly papillary thyroid cancer, the precise nature of this relationship varies across studies and is influenced by multiple factors. The limited information regarding the relationship between IBD and thyroid disorders in children highlights a significant knowledge gap. Since the thyroid plays a critical role in the pediatric population's development, it is essential to promptly recognize and treat thyroid diseases. A thyroid function monitoring and future research exploring the genetic and immunologic connections are essential to enhance our understanding of the interrelation between IBD and thyroid disorders.

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.

We explored the clinical characteristics, treatment, and outcomes of colitis-associated colorectal cancer (CAC) and compared with sporadic colorectal cancer in Taiwan.

In this retrospective study spanning 1987-2022, CACs diagnosed according to endoscopic and pathological reports from 14 tertiary centers were reported to our cohort. Clinical demographics, endoscopic findings, histological results, treatment modalities, and outcomes were analyzed. Sporadic colorectal cancer data were retrieved from the Cancer Registry Annual Report, Ministry of Health and Welfare, Taiwan.

We enrolled 65 patients with CAC (median age: 56 years; male: 66.2%). Distal colon was the most common tumor location (41.5%). Of patients with ulcerative colitis, 77.2% had extensive colitis, and 76.5% had Mayo endoscopic subscores of ≥2. Moreover, 50% of lesions were nonpolypoid with indistinct borders in 66.7%. Signet-ring cell subtype consisted of 12.3%. Surveillance colonoscopy adherence was 78.4%, yet 51.3% interval cancers occurred. Disease stage 0-4 distribution was 15%, 20%, 13.3%, 20%, and 31.7%, respectively. Endoscopic resection was feasible for 14%, whereas 67.7% required surgery. During follow-up (median: 21.5 months), we recorded 23.2% recurrence and 34.5% mortality. Lesions with indistinct borders were associated with adverse outcomes (adjusted odds ratio = 11.5 [1.35-98.16]). Colitis-associated rectal cancers, diagnosed later ( P < 0.001), had worse outcomes than sporadic rectal cancers.

This is the largest Asian CAC cohort study, emphasizing the need for stringent disease control, improving detection, and reducing interval cancers. Signet-ring cell subtype was prevalent. Rectal colitis-associated cancers were diagnosed later with poorer outcomes than sporadic rectal cancers.

Gastrointestinal (GI) cancer is a major health concern, contributing significantly to mortality rates in many regions, including Europe. It affects millions of people worldwide and leads to hundreds of thousands of deaths each year. Early detection and treatment through endoscopic methods play a vital role, providing less invasive and more affordable options compared to traditional surgical procedures. Targeted screening is vital for conditions such as Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), gastric cancer (GC), ampullary carcinoma (AC), and colorectal cancer (CRC), particularly in high-risk populations. Endoscopic surveillance significantly reduces cancer incidence and improves survival rates, highlighting the importance of continuous advancements and updated guidelines to enhance screening efficacy and patient outcomes.

The Traditional Chinese Medicine Formulas (TCMFs) represent a distinctive medical approach to disease treatment and have been utilized in clinical practice for treating intestinal diseases for thousands of years. Recently, TCMFs have received increasing attention due to their advantages of high efficiency, safety, as well as low toxicity, providing promising strategies for preventing colorectal carcinoma (CRC). Nonetheless, the potential mechanism of TCMFs in preventing CRC has not been fully elucidated.

The literature from the past three years was reviewed to highlight the therapeutic effects and underlying mechanisms of TCMFs in preventing CRC.

The keywords have been searched, including "traditional Chinese medicine formulas," "herb pairs," "Herbal plant-derived nanoparticles," et al. in "PubMed" and "China National Knowledge Infrastructure (CNKI)," and screened published articles related to the treatment of intestinal precancerous lesions. This review primarily examined the effectiveness and mechanisms of TCMFs in treating intestinal precancerous lesions, highlighting their significant potential in preventing CRC.

Gegen Qinlian decoction, Shaoyao decoction, Wu Wei Wan, etc., exert substantial therapeutic effects on intestinal precancerous lesions. These therapeutic effects are demonstrated by a reduction in disease activity index scores, suppression of intestinal inflammation, and preservation of body weight and intestinal function, all of which contribute to the effective prevention of CRC. Besides, the classic Chinese herbal pairs and the extracellular vesicle-like nanoparticles of herbaceous plants have demonstrated superior efficacy in the treatment of intestinal precancerous lesions. Mechanistically, protecting the epithelial barrier, regulating gut microbiota as well as related metabolism, modulating macrophage polarization, and maintaining immune balance contribute to the role of TCMFs in CRC prevention.

This review demonstrates the great potential and mechanism of TCMFs in CRC prevention and provides a scientific basis for their utilization in CRC prevention.

Studies on the clinical outcomes after detecting low-grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD) are insufficient. This study evaluated the clinical features, frequency, and risk factors for advanced neoplasia in patients with IBD after an LGD diagnosis.

The medical records of 166 patients with IBD from six university hospitals in Korea from 2010 to 2019 were reviewed retrospectively. LGD was diagnosed in all patients during surveillance. The frequency and risk factors for advanced neoplasia were evaluated, and the clinical features of patients with and without advanced neoplasia were compared.

Advanced neoplasia developed in 12 patients (six with large LGD, three with tubulovillous adenoma, and three with high-grade dysplasia), and all cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo scores, and colitis-associated dysplasia was more common than sporadic lesions (83.3% vs. 29.9%; p<0.001). Multivariate analysis showed that colitis-associated LGD significantly increased the risk of developing advanced neoplasia (odds ratio [OR], 10.516; 95% confidence interval [CI], 2.064-53.577). Among patients with colitis-associated lesions, a significant risk factor for advanced neoplasia was a prior history of LGD (OR, 9.429; 95% CI, 1.330-66.863).

Advanced neoplasia developed in 7.2% of patients with IBD and LGD. Most advanced neoplasms developed from colitis-associated lesions, and the risk was higher in patients with a history of LGD before index colonoscopy.

Inflammatory bowel diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn's Disease (CD), are chronic inflammatory disorders affecting the gastrointestinal tract. The association between IBD and colorectal cancer (CRC) is well-documented. Multiple factors have been identified as contributors to the risk of developing CRC in patients with IBD, including duration of disease, disease extension, family history of CRC, co-existance of primary sclerosing cholangitis (PSC), and potentially the presence of post-inflammatory polyps (PIPs). PIPs, often referred to as pseudopolyps, are polypoid structures that emerge as a result of severe mucosal inflammation. While their presence has been linked to greater disease severity, the role of PIPs in increasing CRC risk remains controversial. Increasing evidence suggests an association between post-inflammatory polyps (PIPs) and the risk of colorectal neoplasia, with PIPs potentially serving as an indicator of this risk through a history of enhanced inflammation. PIPs may also be linked to a distinct patient phenotype, including the presence of other known risk factors. More recent studies suggest that the risk burden (characterized by a high number or by large polyps) may be important. However, the evidence remains inconsistent, with some studies showing no clear association between PIPs and CRC risk after adjusting for other factors, including histological inflammation. In contrast, the data suggest a low rate of malignant transformation of the PIPs themselves. This narrative review aims to summarize the latest evidence regarding the relationship between PIPs and CRC in IBD, with a focus on UC. While some studies suggest that PIPs may serve as markers of higher disease severity and inflammation, their direct contribution to CRC risk remains unclear. Further research is needed to explore the inflammatory and carcinogenic pathways in patients with PIPs to better understand their role in colorectal cancer (CRC) development.

Inflammation is an important physiological response of the organism to restore homeostasis upon pathogenic or damaging stimuli. However, the persistence of the harmful trigger or a deficient resolution of the process can evolve into a state of low-grade, chronic inflammation. This condition is strongly associated with the development of several increasingly prevalent and serious chronic conditions, such as obesity, cancer, and cardiovascular diseases, elevating overall morbidity and mortality worldwide. The current pandemic of chronic diseases underscores the need to address chronic inflammation, its pathogenic mechanisms, and potential preventive measures to limit its current widespread impact. The present review discusses the current knowledge and research gaps regarding the association between low-grade chronic inflammation and chronic diseases, focusing on obesity, cardiovascular diseases, digestive diseases, and cancer. We examine the state of the art in selected aspects of the topic and propose future directions and approaches for the field.

Synbiotics may be useful to mitigate intestinal diseases such as ulcerative colitis. Here we show that combining 13'-carboxychromanol (δT3-13'), a metabolite of vitamin E δ-tocotrienol (δT3) via omega-oxidation, and Lactococcus lactis subsp. cremori (L. cremoris), but neither agent alone, significantly attenuated dextran sulfate sodium (DSS)-induced fecal bleeding and diarrhea, histologic colitis and interleukin 1β in mice. The combination of δT3-13'+L. cremoris also synergistically prevented DSS-caused compositional changes in gut microbiota and enriched beneficial bacteria including Lactococcus and Butyricicoccus. Interestingly, the anti-colitis effect correlated with the concentrations of δT3-13'-hydrogenated metabolite that contains 2 double bonds on the side chain (δT2-13'), instead of δT3-13' itself. Moreover, in contrast to δT3-13', combining δT3 and L. cremoris showed modest anti-colitis effects and did not prevent colitis-associated dysbiosis. In addition, ex vivo anaerobic incubation studies revealed that gut microbes selected by δT3-13' in the animal study could metabolize this compound to δT2-13' via hydrogenation, which appeared to be enhanced by L. cremoris. Overall, our study demonstrates that combining δT3-13' and L. cremoris can synergically prevent dysbiosis, and may be a novel synbiotic against colitis potentially via promoting δT3-13' metabolizers, which in turn contributes to superior beneficial effects of the combination.

Inflammatory bowel disease-related complications are associated with a decreased quality of life, requirement for surgery, and increased morbidity. Endoscopic ultrasound (EUS) is accurate at identifying and characterizing perianal fistulae and abscesses and helps guide treatment decisions. EUS also allows us to accurately assess for mucosal and transmural inflammation and thus can help differentiate Crohn's disease from ulcerative colitis (UC). EUS use can help predict dysplasia in UC, and monitoring transmural inflammation can help assess response to treatment. In addition to diagnostic EUS, therapeutic EUS techniques have been used to endoscopically drain abscesses and bypass strictures in Crohn's disease.

Ulcerative colitis is a chronic inflammatory bowel disease of the colon mucosa associated with a higher risk of colorectal cancer.

This study classified hematoxylin and eosin (H&E) histological images of ulcerative colitis, normal colon, and colorectal cancer using artificial intelligence (deep learning).

A convolutional neural network (CNN) was designed and trained to classify the three types of diagnosis, including 35 cases of ulcerative colitis (n = 9281 patches), 21 colon control (n = 12,246), and 18 colorectal cancer (n = 63,725). The data were partitioned into training (70%) and validation sets (10%) for training the network, and a test set (20%) to test the performance on the new data. The CNNs included transfer learning from ResNet-18, and a comparison with other CNN models was performed. Explainable artificial intelligence for computer vision was used with the Grad-CAM technique, and additional LAIR1 and TOX2 immunohistochemistry was performed in ulcerative colitis to analyze the immune microenvironment.

Conventional clinicopathological analysis showed that steroid-requiring ulcerative colitis was characterized by higher endoscopic Baron and histologic Geboes scores and LAIR1 expression in the lamina propria, but lower TOX2 expression in isolated lymphoid follicles (all p values < 0.05) compared to mesalazine-responsive ulcerative colitis. The CNN classification accuracy was 99.1% for ulcerative colitis, 99.8% for colorectal cancer, and 99.1% for colon control. The Grad-CAM heatmap confirmed which regions of the images were the most important. The CNNs also differentiated between steroid-requiring and mesalazine-responsive ulcerative colitis based on H&E, LAIR1, and TOX2 staining. Additional classification of 10 new cases of colorectal cancer (adenocarcinoma) were correctly classified.

CNNs are especially suited for image classification in conditions such as ulcerative colitis and colorectal cancer; LAIR1 and TOX2 are relevant immuno-oncology markers in ulcerative colitis.

Fecal calprotectin (FC) is a promising biomarker for assessing ulcerative colitis (UC) endoscopic activity. However, the optimal FC cutoff to identify each Mayo endoscopic subscore (MES) remains inconclusive.

The electronic medical records of 177 adult UC patients evaluated at Mayo Clinic Rochester from January 2017 to March 2023 were retrospectively reviewed, obtaining clinical data and US-based Werfen Diagnostics FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES.

The median interval between FC collection and endoscopy was 2 days. Fecal calprotectin showed strong positive correlations with MES (Spearman's r = 0.709; P < .01) and other clinical parameters. Fecal calprotectin cutoff of 60 mcg/g effectively distinguished MES 0 from MES 1-3 (sensitivity, 0.78; specificity, 0.97; area under the receiver operating characteristic curve [AUC], 0.901) and predicted clinical remission (Total Mayo Score ≤2 and no subscore >1; sensitivity, 0.83; specificity, 0.98; AUC, 0.921). Fecal calprotectin cutoff of 110 mcg/g effectively differentiated MES 0-1 from MES 2-3 (sensitivity, 0.86; specificity, 0.87; AUC, 0.915), while a cutoff of 310 mcg/g distinguished MES 0-2 from MES 3 (sensitivity, 0.80; specificity, 0.76; AUC, 0.820).

This study supports the reliability and applicability of FC as a valuable marker of endoscopic inflammation, particularly in distinguishing MES 0 from MES 1-3 using the FC cutoff of 60 mcg/g. Sensitivity analysis demonstrated robust results.

While epidemiological studies have linked statin use to a reduced risk of advanced colorectal adenomas, its impact on colorectal cancer (CRC) risk in patients with inflammatory bowel disease (IBD) remains unclear. To our knowledge, no meta-analysis to date has specifically examined this association. Therefore, we conducted a systematic review and meta-analysis of the available observational studies to investigate the risk of CRC associated with statin use in IBD patients.

We searched three databases for articles published in English before September 2024, focusing on the protective effects of statins against CRC in IBD patients. We calculated multivariate odds ratios (ORs) and their 95% confidence intervals (CIs) to assess this association. A random-effects meta-analysis was conducted using the generic inverse variance method.

The meta-analysis included 4 studies encompassing 22,250 IBD patients, 6,712 of whom were statin users. The methodological quality of three of the studies was deemed high. We found a significantly lower risk of CRC in statin users compared to non-users, with a pooled relative risk of 1.88 (95% CI 1.54-2.30). Sensitivity analyses confirmed the consistency of these findings.

Statin use appears to be associated with a reduced risk of CRC in patients with IBD. However, given the limited number of studies available, further prospective research with large sample size is necessary to confirm the potential chemopreventive role of statins in this population.

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.

The incidence of patients diagnosed with either breast cancer (BC) or inflammatory bowel disease (IBD) is increasing each year. IBD has been shown to be strongly associated with the development of a variety of solid tumors, but the relationship with breast cancer is not yet definitive. We explored the causative relationship between IBD and BC using a Mendelian randomization (MR) strategy. MR-Egger regression, weighted median (WM), simple median (SM), maximum likelihood (ML), and inverse variance weighting (IVW) methods were among the analytical techniques used in this work. The examination of heterogeneity was conducted by the use of Cochran's Q test and Rucker's Q test. The sensitivity analysis in this study used the IVW and MR-Egger methodologies. The results of our investigation suggested that IBD had a beneficial impact on estrogen receptor-negative (ER-) breast cancer (odds ratio (OR) = 0.92, P = 0.02). The study did not find a significant association between IBD and the risk of developing overall breast cancer (OR = 0.99, P = 0.60), as well as estrogen receptor-positive (ER+) breast cancer (OR = 1.02, P = 0.60) specifically. In addition, our study findings indicated that there was a detrimental association between ER+ breast cancer and IBD as determined using reverse MR analysis (OR = 1.07, P = 0.04). Furthermore, this analysis failed to observe any significant association between overall breast cancer (OR = 1.07, P = 0.07) or ER- breast cancer (OR = 0.99, P = 0.89) and IBD. Our bidirectional MR study yielded a correlation between IBD and some specific hormone receptor status of BC.

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.

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).

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).

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.

Background and study aims Patients with primary sclerosing cholangitis and inflammatory bowel disease (IBD) have a high risk of colorectal cancer. There is no agreement on the best technique for surveillance for colorectal neoplasia. We aimed to assess whether chromoendoscopy and/or high-definition endoscopy is associated with increased detection of neoplasia in patients with primary sclerosing cholangitis undergoing surveillance compared with when they were not used. Patients and methods This was a single-center, retrospective, observational study designed to analyze differences in the detection of neoplasia (adenomatous and serrated) among patients with primary sclerosing cholangitis and IBD who underwent annual surveillance between 2010 and 2020. Multilevel logistic regression was used to adjust for confounders. Results Ninety-one patients were identified, resulting in 359 colonoscopies with 360 person-years of follow up. Over the study period, 22 of 91 patients (24%) had at least one neoplastic lesion identified; however, the mean neoplastic lesion rate was 0.87 (54/63) for the primary sclerosing cholangitis-ulcerative colitis subgroup compared with 0.24 (4/17) for the primary sclerosing cholangitis-Crohn's disease subgroup. Chromoendoscopy was associated with a significantly higher detection rate for neoplasia (odds ratio [OR] 5.58, 95% confidence interval [CI] 2.08-14.9, P =0.001), and this association remained after adjusting for confounders, including high-definition endoscopy. High-definition endoscopes had a higher rate of neoplasia detection, but the significance was lost after adjustment for confounders, including chromoendoscopy (OR 1.93, 95% CI 0.69-5.40, P =0.21). Conclusions Chromoendoscopy is associated with a higher detection rate for neoplasia in patients with primary sclerosing cholangitis and IBD even with high-definition colonoscopes.

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.

Inflammatory bowel disease [IBD] patients are at increased risk of developing colorectal neoplasia [CRN]. In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard [cold snare] polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity [size, delineation, morphology, surface architecture, submucosal fibrosis/invasion] to maximise the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. Whereas [sub]total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualisation with shortened intervals for at least 5 years after treatment of CRN.