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: The relationship between autoimmune diseases (AIDs) and cancer is unclear and this study aimed to investigate the relationship between AIDs and cancer at the genetic level using Mendelian randomization (MR). Methods: The study employed two-sample MR and meta-analysis to investigate the association between AIDs and 33 types of cancer, following STROBE-MR guidelines. Single nucleotide polymorphisms (SNPs) associated with AIDs were used as instrumental variables, with data from FinnGen, UK Biobank, and other databases. MR analyses included sensitivity checks, heterogeneity assessments, and reverse causality tests, using multiple MR methods (inverse-variance weighted (IVW), weighted median, MR-Egger, etc.). Meta-analysis was performed on validated results to confirm findings, with statistical analyses conducted using R software. Results: The results identified eight significant associations in both discovery and replication stages. Key findings include that myasthenia gravis (MG) significantly increases the risk of oral cavity cancer, multiple sclerosis (MS) is linked to increased risks of chronic lymphocytic leukemia (CLL) and small intestine cancer, and ulcerative colitis (UC) has mixed effects, reducing the risk of uterine cervix and larynx cancers, but increasing risks for pancreatic and bladder cancers. Meta-analysis confirmed eight secondary findings, highlighting pathogenic associations such as type 1 diabetes with esophagus cancer and protective effects like systemic lupus erythematosus (SLE) against acute myelocytic leukemia. Conclusions: This study provides evidence of a causal relationship between multiple AIDs and different cancer risks at the genetic level and provides a reference for the health management of patients with AIDs.

Over a 14-year period from 2010 to 2023, we treated 86 psoriasis patients with various biological agents at Asahikawa City Hospital, and 12 malignancies occurred in 11 of the patients. The numbers of malignancies by organ were as follows: four urogenital, three hematological, two gastrointestinal, one breast, one thyroid, and one lung. In two patients without cancer-related symptoms, elevated serum Krebs von den Lungen-6 levels led to the detection of intrahepatic cholangiocarcinoma or thyroid cancer, and they did not have interstitial lung disease. Dermatologists should be aware of the increased incidence of malignancy in patients with psoriasis requiring treatment with biologics.

Inflammatory Bowel Disease (IBD) is a lifelong chronic disease affecting any part of the gastrointestinal tract with a predilection for the terminal ileum. IBD patients require repeat imaging throughout the course of their disease, necessitating a safe, noninvasive, available, and repeatable method. Imaging is required at diagnosis, routine surveillance, and acute exacerbation of disease. Ultrasound imaging meets these demands with a high degree of accuracy and wide patient acceptance. Ultrasound provides high-resolution imaging and is excellent for detailed evaluation of the bowel wall and surrounding soft tissues. Regular greyscale bowel evaluation and color Doppler imaging now have accepted standards for evaluating disease activity based on wall thickness, perienteric inflammatory fat, and blood flow, which is invaluable in staging and grading disease. High-resolution dynamic real-time imaging on ultrasound has the ability to show functional as well as morphologic detail, including dysfunctional peristalsis associated with bowel stricture and incomplete mechanical bowel obstruction. Fibrostenotic and penetrating complications of IBD may be associated with an acute or chronic presentation that is easily assessed using ultrasound. Newer software technologies for ultrasound, including Contrast-Enhanced ultrasound and Shear wave elastography, have transformed ultrasound from a basic preliminary imaging technique into a highly sophisticated modality that is now competitive with CT and MR enterography for managing IBD patients. Our long experience with ultrasound of the bowel suggests that the new best practice would include ultrasound as the first test for evaluation of the bowel at any stage of the disease.

Over the past decades, an increased importance has been given to gastrointestinal (GI) endoscopy in the management of children with inflammatory bowel diseases (IBD), considering that mucosal healing has been recognized as the optimal endpoint in the treat-to-target paradigm. The recent advances in technology and anesthesia have facilitated the comprehensive evaluation of the GI tract. In this review, we will discuss the role of ileocolonoscopy, upper GI endoscopy, and device-assisted enteroscopy in the work-up and management of pediatric Crohn's disease (CD) and ulcerative colitis, with particular attention on non-invasive endoscopic techniques, such as wireless capsule endoscopy. We will also analyze the most commonly used endoscopic scoring systems, including small bowel scoring systems and endoscopic recurrence grading of neo-terminal ileum CD. Moreover, we will focus on the endoscopic management of complications, such as strictures, that commonly require surgery. Lastly, we will discuss cancer surveillance in children with IBD, with particular consideration of the role of high-definition endoscopic equipment and chromoendoscopy in dysplasia detection rates.

Histomorphology is a powerful and cost-efficient tool for evaluating inflammatory and neoplastic conditions. Inflammatory bowel disease (IBD) is a widespread condition with globally rising incidences, and a lot of research is done to better understand the pathogenesis of IBD and to identify potential therapeutic approaches. However, standardized and reproducible scores for the histomorphological evaluation of murine IBD models are lacking. Therefore, we aimed to develop an easy-to-use and reproducible score for standardized assessment of colitis and associated cancer models.

In this study, samples from three different colitis models with and without associated cancer formation were analyzed to develop a universal, robust, and reproducible score for the grading of murine colitis models using the following three parameters: 1. Extent of leucocyte infiltration, 2. Tissue damage, 3. Architectural disruption of the mucosa.

A scoring system was established for different kinds of colitis models (genetically induced enterocolitis, genetically induced metabolic injury, and chemically induced colitis-associated cancer) and all stages of the disease, from mild inflammatory changes to severe inflammation with neoplastic changes as the extreme extent of IBD. The scoring scheme is easy to use, can easily be learned, and proves to have a high interrater reliability.

We propose a robust histological scoring system for the assessment of murine colitis and colitis-associated cancer models, giving more researchers access to conclusive and reliable histological assessment.

Clinicopathological differences exist between ulcerative colitis-associated colorectal cancer (UC-CRC) and sporadic colorectal cancer (S-CRC). However, differences in the prognosis remain controversial, and the reason for these differences remains unclear. We therefore assessed the differences between patients with UC-CRC and S-CRC.

This was a matched-pair analysis of the clinicopathological characteristics and prognosis of patients with UC-CRC and S-CRC who underwent colorectal resection between January 2000 and December 2021 at two institutions. Patients were matched according to age, sex, date of surgery, tumor location, and Union for International Cancer Control (UICC) stage.

A total of 5992 patients underwent surgery for CRC at the two institutions, and 288 patients (48 with UC-CRC and 240 with S-CRC) were matched in this study. Patients with UC-CRC underwent more invasive surgery and had a longer operative time than those with S-CRC, but there was no marked difference in postoperative complications or perioperative mortality. Long-term outcomes showed a similar 5-year overall survival (OS) for UC-CRC and S-CRC (86.5% versus 88.8%, p = 0.742); however, in stage 3 patients, patients with UC-CRC had a poorer 5-year OS than those with S-CRC (51.4% versus 83.8%, p = 0.032). The first recurrence sites in stage 3 UC-CRC were peritoneal dissemination followed by the bones, while those in S-CRC were the liver and pulmonary system.

Despite no significant differences in surgical outcomes, patients with UC-CRC had a poorer prognosis than those with S-CRC at stage 3. The recurrence patterns in UC-CRC differed from those in S-CRC, suggesting a possible prognostic difference.

Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined. A better understanding of this phenomenon could improve the identification of high-risk populations. In this study, we characterized these relationships with experiments using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and DSS/azoxymethane (AOM)-induced CRC (DSS/AOM-CRC) in wild-type and conditional transgenic mice of PCa. We showed that DSS-induced UC was more severe in mice with PCa and resulted in the development of CRC in the absence of AOM. We further showed that PCa-free mice that developed DSS-induced UC also showed histological changes in the normal prostate that resembled proliferative inflammatory atrophy. Finally, we used immunohistochemical immune profiling to show that mice with PCa-induced chronic systemic inflammation accumulated Gr1+ myeloid cells in the normal colon and exposure to DSS further enriched these cells in active colitis regions and colon tumors. Our study provides evidence to support a link between systemic chronic inflammation and cancer.

Individuals with inflammatory bowel disease (IBC) and high-risk individuals are advised to discuss participation with their doctor and not to participate in colorectal cancer (CRC) screening. Yet a substantial proportion still participate in the Danish faecal immunochemical test (FIT) screening and have a higher positive FIT rate than the average-risk population. We estimated the risk of false-positive screening among individuals with inflammatory bowel disease and high-risk individuals to improve recommendations regarding screening participation. We included 71,871 FIT-positive participants (2014-2017) who had a subsequent colonoscopy within 3 months. Screening outcome within 180 days was established by using registers. We determined that 26,591 of the included participants had a false-positive screening. Participants with IBC or high CRC risk had a significantly higher risk of getting a false-positive screening than the average risk population, resulting in too many screening-related colonoscopies being performed among these individuals, indicating a need to update the screening protocols.

Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.

This study compares surgical and oncological outcomes in patients with Crohn's disease (CD)-related colorectal cancer (CRC) to those with sporadic CRC.

Patients treated between 1983 and 2013 were matched by stage, age, gender, American Society of Anesthesiologists (ASA), cancer site, and adjuvant chemotherapy.

For stages I and II, 107 patients were matched (58.9% male, mean age 59 years, 59.8% with ASA score 3). Tumor sites included the right (17.7%), transverse (4.7%), left colon (15.9%), and rectum (61.7%). CD patients exhibited longer operative times, higher pT stages, and 2.60 times the odds of postoperative complications (p = 0.03). Overall and disease-free survival were similar. For stage III, 54 patients were matched (57.4% male, mean age 54 years, 46.3% with ASA score 3). The cancer site distribution was right (29.7%), transverse (3.7%), left colon (18.5%), and rectum (48.1%). CD patients had longer operative times, increased blood loss, more involved lymph nodes, higher pT- and pN-stages. The rates of postoperative complications were not different (p = 0.19). CD-related CRC patients had similar overall (p = 0.06), and local recurrence-free survival (p = 0.07).

Despite facing worse perioperative and pathological characteristics, survival differences in stages I-III CD-related CRC compared with sporadic CRC patients were not significantly different.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) Commentary is to discuss the risks of various malignancies in patients with inflammatory bowel diseases (IBD) and the impact of the available medical therapies on these risks. The CPU will also guide the approach to the patient with IBD who develops a malignancy or the patient with a history of cancer in terms of IBD medication management.

This CPU was commissioned and approved by the AGA Institute CPU committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in the field, and it reflects the experiences of the authors who are experts in the diagnosis and management of IBD.

Background & objectives Crohn's disease (CD) is associated with a higher risk of malignancy, which is attributed to disease behaviour and the usage of immunosuppressants. The burden of malignancy in CD is scarcely reported from Asia. We report real-world data on CD-related malignancy from a northern Indian cohort. Methods This retrospective analysis included individuals with CD who were followed up at the All India Institute of Medical Sciences, New Delhi, from 2005 to 2021. The standardized incidence ratio (SIR) was used to calculate the relative risk of malignancy in CD affected individuals compared to the general population. Results In this study, 952 study participants were included, with a mean age at diagnosis of 36.9±15.11 yr; 61.1 per cent were male. The median follow-up duration was 34 months [IQR (interquartile range): 19-73]. Most study participants received steroids (76.7%), immunomodulators (68.7%), or anti-TNF therapy (10.8%). The overall incidence of malignancy was 1.05 per cent, indicating a 10.45 times higher risk in CD [SIR: 10.45; 95% Confidence interval (CI):4.98-17.96]. Eight out of 826, 1 of 106 and 1 of 25 study participants developed malignancy in the first, second and third decades, respectively. The cumulative risk of malignancy was 2.7, 5.5, and 13.4 per cent in the first, second, and third decades, respectively. Regarding bowel malignancies, one study participant each developed ileocaecal adenocarcinoma, anorectal adenocarcinoma, malignant rectal fibrous histiocytoma, and gastric adenocarcinoma. Extraintestinal malignancies included single cases each of follicular neoplasia of the thyroid, neuroendocrine tumour of the pancreatic tail, breast cancer, hepatocellular cancer, oral cancer, and prostate cancer. No cases of lymphoma or skin malignancy were reported. Interpretation & conclusions At 30 yr, the cumulative risk of malignancy among Indian CD-affected individuals was 13.4 per cent, with a SIR of 10.45 (95% CI: 4.98- 17.96). The risk increased with increasing age at disease onset and duration.

Colonoscopy withdrawal time (CWT) of at least 6-9 minutes is the minimum time needed for adequate adenoma detection in the general population. The ideal CWT in patients with inflammatory bowel disease (IBD) has not been determined. We aimed to identify the optimal CWT associated with the detection of visible dysplasia in patients with IBD.

This is a retrospective study from 1/1/2017 to 9/1/2022 of adult patients with IBD in endoscopic healing undergoing surveillance via high-definition white light colonoscopy. The primary outcome was the association of CWT with visible dysplasia detection.

A total of 259 patients (mean age 56 ± 14.8 years; 51.3% female, 68% with ulcerative colitis; 8.9% with primary sclerosing cholangitis) underwent 330 colonoscopies. Patients with visible dysplasia were more likely to be older (P < .001) and have a personal history of visible dysplasia (P < .001) and invisible dysplasia (P = .023). The mean CWT was significantly longer in the visible dysplasia group at 26 minutes (interquartile range [IQR] 20-38.5) vs. 21 minutes (IQR 15-28) in procedures without visible dysplasia (P < .001). On multivariable analysis, increased age (P < .001), increased CWT (P = .001), and personal history of visible dysplasia (P = .013) were independently associated with the detection of visible dysplasia. A CWT of ≥15 minutes (odds ratio [OR] 2.71; 95% confidence interval [CI], 1.11-6.6; P = .02] and not ≥9 minutes (OR 2.57; 95% CI, 0.33-20.2; P = .35) is significantly associated with detection of visible dysplasia.

For patients with IBD undergoing surveillance via high-definition white light colonoscopy, the mean CWT was independently associated with the detection of visible dysplasia.

Toll-like receptors (TLRs) are implicated in the pathogenesis and progression of inflammation-associated cancers, except their role in regulating innate immunity. Specifically, a berrant expression of TLR6 has been observed in colorectal cancers (CRC). However, the effect of abnormal TLR6 expression on CRC remians unclear. Therefore, the present study evaluated TLR6 expression in CRC, its effect on CRC proliferation, and its underlying mechanism.

The expression of TLR6 in CRC was assessed using data from TCGA, GTEx, and HPA datasets and immunohistochemical assays of tumor tissues from patients with CRC. In human CRC cell lines, TLR6 signaling was activated using the TLR6 agonist Pam2CSK4 and was blocked using antiTLR6-IgG; subsequently, cell growth, migration, invasion, cell cycle, and apoptosis were compared in CRC cells. The levels of the anti-apoptotic protein Bcl-2 and the apoptotic protein Bax were identified using western blotting. In addition, the effect of TLR6 knockdown by shRNAs in CRC cells was observed both in vitro and in vivo. Nuclear factor κB (NF-κB) level was evaluated using immunofluorescence and western bolt.

TLR6 expression was significantly downregulated in CRC tissues. The activation of TLR6 by Pam2CSK4 (100 pg/mL to 10 ng/mL) inhibited the proliferation of CRC cells. Compared with blocking TLR6 signaling using antiTLR6-IgG, activating TLR6 signaling significantly inhibited CRC cell growth, migration, and invasion as well as decreased the proportion of cells in the S and G2/M phases and promoted apoptosis. Furthermore, the knockdown of TLR6 by shRNA promoted the biological activity of CRC cells both in vitro and in vivo. Moreover, the activation of TLR6 signaling by Pam2CSK4 significantly downregulated NF-κB and Bcl-2 levels but upregulated Bax levels.

The findings of this study demonstrate that TLR6 may play a inhibitive role in CRC tumorigenesis by suppressing the activity of NF-κB signaling.

Patients with inflammatory bowel disease (IBD) are at increased risk of malignancy and infection compared to the general population.

We aim to identify risk factors for malignancy or serious infection in our IBD cohort.

Patients with IBD from a single tertiary referral centre were included. Demographic and clinical details, including immunosuppressant exposure, were collected and medical records retrospectively screened for adverse events, including malignancy or infection requiring hospitalisation. Logistic regression was used to evaluate risk factors for adverse events.

Five hundred and forty-nine patients with IBD (340 Crohn disease (CD) and 209 ulcerative colitis (UC)) were studied. Forty-eight malignancies, including 39 (81.3%) non-melanoma skin cancers, 3 (6.3%) haematologic malignancies and 6 (15.4%) solid-organ malignancies, were identified, and 92 cases of serious infection were detected. IBD duration (odds ratio (OR) = 1.08; 95% confidence interval (CI) = 1.03-1.13) and ileocolonic CD (OR = 4.96; 95% CI = 1.13-21.71) were associated with increased odds of overall cancer. Compared with patients not previously exposed to the given class of immunosuppression assessed, the development of overall malignancy was not higher with thiopurine exposure (OR = 1.00; 95% CI = 0.50-2.24) or anti-tumour necrosis factor-alpha (TNF-α) exposure (OR = 0.78; 95% CI = 0.37-1.64). Similarly, compared with patients not exposed, infection risk was not affected by thiopurine (OR = 0.74; 95% CI = 0.46-1.20) or anti-TNF exposure (OR = 0.60; 95% CI = 0.38-0.95).

Factors including ileocolonic CD and increasing IBD duration were associated with higher malignancy risk in this cohort. Compared with non-exposure, patients exposed to thiopurines were not at increased risk of malignancy or serious infection. Similarly, patients exposed to anti-TNF treatment did not experience increased rates of malignancy or serious infection compared to patients not exposed to this treatment.

Inflammatory bowel disease (IBD), characterized primarily by gastrointestinal inflammation, predominantly manifests as Crohn's disease (CD) and ulcerative colitis (UC). It is acknowledged that Inflammation plays a significant role in cancer development and patients with IBD have an increased risk of various cancers. The progression from inflammation to carcinogenesis in IBD is a result of the interplay between immune cells, gut microbiota, and carcinogenic signaling pathways in epithelial cells. Long-term chronic inflammation can lead to the accumulation of mutations in epithelial cells and the abnormal activation of carcinogenic signaling pathways. Furthermore, Immune cells play a pivotal role in both the acute and chronic phases of IBD, contributing to the transformation from inflammation to tumorigenesis. And patients with IBD frequently exhibit dysbiosis of the intestinal microbiome. Disruption of the gut microbiota and subsequent immune dysregulation are central to the pathogenesis of both IBD and colitis associated colorectal cancer (CAC). The proactive management of inflammation combined with regular endoscopic and tumor screenings represents the most direct and effective strategy to prevent the IBD-associated cancer.

Real-world evidence is needed to determine the value of tofacitinib (TOFA) for the treatment of ulcerative colitis (UC).

To assess the safety and effectiveness of TOFA in clinical practice.

TOFA-UC is a multicenter, observational study performed among the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with UC starting TOFA from its introduction in Sicily (July 2021) to July 2022 were included.

111 patients were included (mean follow-up: 31.7 ± 14.9 weeks; biologic-experienced: 92.8%). Nineteen adverse events were reported (17.1%; incidence rate: 28.2 per 100 patient years), including 11 cases of hypercholesterolemia and 3 infections (no cases of herpes zoster reactivation. At week 8, the rates of clinical response, steroid free clinical remission, and CRP normalization were 74.8%, 45.0%, and 56.9%, respectively, and 68.5%, 51.4%, and 65.2%, respectively, at the end of follow-up. Eighteen patients experienced a loss of response after successful induction (21.7%; incidence rate: 33.2 per 100 patient years). Twenty-six patients (23.4%) discontinued TOFA over time, of whom 3 due to AEs, and 23 to non response or loss of response.

TOFA is safe and effective in patients with UC, including those with history of multiple failures to biological therapies.

Small bowel carcinomas are rare in the general population, but the incidence is increasing. Patients with inflammatory bowel diseases (IBDs) are at significantly higher risk of small bowel adenocarcinomas than their non-IBD counterparts, with Crohn's patients having at least a 12-fold increased risk and ulcerative colitis patients with a more controversial and modest 2-fold increased risk compared with the general population. IBD patients with small bowel carcinomas present with nonspecific symptoms that overlap with typical IBD symptoms, and this results in difficulty making a preoperative diagnosis. Cross-sectional imaging is rarely diagnostic, and most cancers are found incidentally at the time of surgery performed for an IBD indication. As such, most small bowel carcinomas are found at advanced stages and carry a poor prognosis. Oncologic surgical resection is the treatment of choice for patients with locoregional disease with little evidence available to guide adjuvant therapy. Patients with metastatic disease are treated with systemic chemotherapy, and surgery is reserved for palliation in this population. Prognosis is poor with few long-term survivors reported.

Background and study aims Chronically inflamed colonic mucosa is primed to develop dysplasia identified at surveillance colonoscopy by targeted or random biopsies. We aimed to explore the effect of mucosal inflammation on detection of visible and "invisible" dysplasia and the concordance between the degree of endoscopic and histologic inflammation. Patients and methods This was a 6-year cross-sectional analysis of endoscopic and histologic data from IBD. A multinomial model was created to estimate the odds for a specific lesion type as well as the odds of random dysplasia relative to the degree of inflammation. Kappa statistics were used to measure concordance between endoscopic and histologic inflammation. Results A total of 3437 IBD surveillance colonoscopies between 2016-2021 were reviewed with 970 procedures from 721 patients containing 1603 visible lesions. Kappa agreement between histologic and endoscopic degree of inflammation was low at 0.4. There was a positive association between increased endoscopic inflammation and presence of tubulovillous adenomas (TVAs) (odds ratio [OR] 2.18; 95% confidence interval [CI] 1.03-4.62; P =0.04). Among cases with visible lesions, the yield of concomitant random dysplasia was 2.7% and 1.9% for random indefinite dysplasia. The odds of random dysplasia significantly increased as the degree of endoscopic and histologic inflammation increased (OR 2.18, 95%CI 1.46-3.26; P <0.001 and OR 2.75; 95%CI 1.65-4.57, P <0.001, respectively. The odds of indefinite random dysplasia also significantly increased as endoscopic and histologic inflammation increased (OR 2.90; 95%CI 1.85, 4.55, P <0.001 and OR 1.98; 95%CI 1.08, 3.62, P <0.035, respectively. Conclusions Endoscopic and histologic inflammation are associated with higher odds of finding TVAs and random low-grade, high-grade, and indefinite dysplasia. Concordance between histologic and endoscopic inflammation severity is low.

The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) has been well documented in the literature. The present study aimed to assess the characteristics and outcomes of rectal cancer in patients with IBD. This study was a retrospective review of a prospectively maintained IRB-approved database at Cleveland Clinic Florida. Rectal cancer patients with or without IBD treated with curative surgery between 2016 and 2020 were compared for demographics, disease characteristics, and pathologic and oncologic outcomes. The primary outcomes were 3-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were clinicopathologic outcomes including disease stage, tumor histology and histologic features, and treatments received. 238 patients with rectal cancer were included, 15 (6.3%) of whom had IBD. IBD patients were significantly younger (52.9 vs 60.3 years, p = 0.033), presented more often with cT1-2 tumors (64.3% vs 30.4%, p = 0.008), and signet-ring cell pathology (14.3% vs 2%, p = 0.02). IBD patients received neoadjuvant chemoradiation less often (40% vs 72.6%, p = 0.029) and had shorter time between diagnosis and surgery (7.5 vs 25 weeks, p = 0.013) than did non-IBD patients. Both groups had similar OS (36 vs 34.7 months, p = 0.431) and DFS (36 vs 32.9 months, p = 0.121). IBD patients with rectal cancer tend to present at a younger age, with a less invasive disease, and signet-ring carcinomas, and receive neoadjuvant treatment less often than non-IBD patients. Based on low level of evidence, IBD and non-IBD rectal cancer patients might have similar survival.

Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.

Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.

Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.

Crohn disease is a chronic inflammatory disease that can affect the entire gastrointestinal tract. The pathophysiology of this disease characteristically involves transmural inflammation, which predisposes patients to various gastrointestinal cancers such as colon cancer. Although the increased risk of gastrointestinal cancers in Crohn disease has been well established, the risk of extra-gastrointestinal cancers remains unknown. We sought to study the risk of breast cancer in patients with Crohn disease.

The data for this retrospective study were compiled using the International Classification of Disease Ninth Revision (ICD-9) and ICD 10th Revision (ICD-10) codes from the national Health Insurance Portability and Accountability Act (HIPAA)-compliant PearlDiver database from 2010 to 2019. Patients were matched for age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were implemented to assess Chi-squared, logistic regression, and odds ratio.

The database query resulted in 70,027 patients in both the control and Crohn disease groups. The incidence of breast cancer was 4,087 in the control group compared to 654 in the Crohn disease group. The P value was < 2.2 × 10-16 and the odds ratio was 0.15 (95% confidence interval (CI)). Patients without Crohn disease had an increased prevalence of breast cancer throughout all age ranges compared to patients with Crohn disease. Additionally, patients without Crohn disease had higher rates of breast cancer throughout the four major regions of the United States. In terms of healthcare costs, patients with breast cancer and a history of Crohn disease paid $23.87 more per hospital visit compared to patients with breast cancer and no history of Crohn disease.

The results of this study indicate a statistically significant correlation between Crohn disease and a reduced incidence of breast cancer. This finding is true across all age groups and across the United States. Further study is required to investigate a possible mechanism between the pathophysiology of Crohn disease ultimately leading to reduced tumorigenesis in the breast.

Recent studies have shown that inflammatory bowel disease (IBD) is associated with bladder cancer (BC) incidence. But there is still a lack of understanding regarding its pathogenesis. Thus, this study aimed to identify potential hub genes and their important pathways and pathological mechanisms of interactions between IBD and BC using bioinformatics methods.

The data from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to screen common differentially expressed genes (DEGs) between IBD and BC. The "clusterProfiler" package was used to analyze GO term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment in DEGs. After that, we conducted a weighted gene co-expression network analysis (WGCNA) on these DEGs to determine the vital modules and genes significantly related to BC. Protein-protein interaction (PPI) networks was used to identify hub genes. Further, the hub genes were used to develop a prognostic signature by Cox analysis. The validity of the ten hub DEGs was tested using three classification algorithms. Finally, we analyzed the microRNAs (miRNA)-mRNA, transcription factors (TFs)-mRNA regulatory network.

Positive regulation of organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway were the major enriched pathways for the common DEGs. PPI networks identified three hub proteins (AURKB, CDK1, and CCNA2) with high connectivity. Three machine-learning classification algorithms based on ten hub genes performed well for IBD and BC (accuracy > 0.80). The robust predictive model based on the ten hub genes could accurately classify BC cases with various clinical outcomes. Based on the gene-TFs and gene-miRNAs network construction, 9 TFs and 6 miRNAs were identified as potential critical TFs and miRNAs. There are 13 drugs that interact with the hub gene based on gene-drug interaction analysis.

This study explored common gene signatures and the potential pathogenesis of IBD and BC. We revealed that an unbalanced immune response, cell cycle pathway, and neutrophil infiltration might be the common pathogenesis of IBD and BC. Molecular mechanisms for the treatment of IBD and CC still require further investigation.

Novel reliable biomarkers of inflammatory bowel disease (IBD) are clinically imperative due to potential limitations of endoscopic techniques. MicroRNAs (miRNAs) have emerged as non-invasive biomarkers of IBD; however, the full disease-specific miRNAs signature for IBD subtypes remains elusive. We evaluated the diagnostic role of circulating miR-486 and miR-25 in IBD patients and their potential ability to discriminate IBD subtypes; ulcerative colitis (UC) and Crohn's disease (CD). Sixty UC patients, 60 CD patients, and 60 healthy controls were recruited. Serum miRNA expression was determined using RT-qPCR. Bioinformatics was employed for target gene and protein-protein interaction (PPI) network analyses. Serum miR-486 was upregulated in CD patients, but didn't change in UC patients compared to controls. Conversely, serum miR-25 was decreased in both CD and UC patients compared to controls. Only miR-486 was differentially expressed between UC and CD patients. Receiver-operating characteristic analysis revealed that serum miR-486 was superior in CD diagnosis (AUC=0.945) and significantly distinguished CD and UC patients, whereas miR-25 showed discriminative potential for both UC and CD from controls. In the multivariate logistic analysis only miR-486 was associated with the risk of CD diagnosis. Serum miR-486 was correlated with CD activity index and location of disease in CD patients, whereas miR-25 was correlated with the type/extent of UC. PPI network analysis revealed common target genes and signaling pathways for both miRNAs. Conclusively, serum miR-486 and miR-25 might serve as new biomarkers of IBD, with serum miR-486 could be employed in risk stratification of IBD subtypes and has the ground for clinical utility in CD diagnosis, whereas miR-25 has potential for UC and CD diagnosis.

Prior epidemiological observational studies have duly documented a correlative link between inflammatory bowel disease (IBD) and bladder cancer (BC); however, the establishment of a definitive causal relationship has remained elusive. The principal objective of this meticulous investigation was to rigorously evaluate the causal nexus between IBD and BC, employing the robust methodology of Mendelian randomization (MR) analysis.

We meticulously performed both univariate and multivariate Mendelian randomization (MVMR) analyses employing publicly accessible genome-wide association study (GWAS) data. The central approach employed for our investigations was inverse variance weighting (IVW) method, while diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger.

In the univariate MR analysis, no causal link was observed between genetic prediction of IBD and BC. Furthermore, both Crohn's disease (CD) and ulcerative colitis (UC) showed no causal association with BC. The consistent association between CD and UC in the MVMR analysis supports this finding.

This study found no genetic basis for the causative association of IBD and BC. It is crucial to emphasize that further comprehensive investigations are warranted to delve into the intricate underlying mechanisms that may contribute to these associations.

The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers.

Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD patients, 5956 Crohn's disease (CD) patients, and 6968 ulcerative colitis (UC) patients. Three sources of cancer GWAS were selected as outcome data. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of IBD on 32 extracolonic cancers. The meta-analysis was applied to assess the combined causal effect with multiple MR results.

IBD, CD, and UC have potential causal associations with oral cavity cancer (IBD: OR = 1.180, 95% CI: 1.059 to 1.316, P = 0.003; CD: OR = 1.112, 95% CI: 1.008 to 1.227, P = 0.034; UC: OR = 1.158, 95% CI: 1.041 to 1.288, P = 0.007). Meta-analysis showed a significant positive causal relationship between IBD and breast cancer (OR = 1.059; 95% CI: 1.033 to 1.086; P < 0.0001) as well as a potential causal relationship between CD and breast cancer (OR = 1.029; 95% CI: 1.002 to 1.055; P = 0.032) based on combining multiple MR results.

This comprehensive MR analysis suggested that genetically predicted IBD, as well as its subtypes, may be a risk factor in the development of oral cavity and breast cancer.

Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory disorders of the gastrointestinal tract, frequently associated with extraintestinal manifestations (EIMs) that can severely affect IBD patients' quality of life, sometimes even becoming life-threatening. Respiratory diseases have always been considered a rare and subsequently neglected extraintestinal manifestations of IBD. However, increasing evidence has demonstrated that respiratory involvement is frequent in IBD patients, even in the absence of respiratory symptoms. Airway inflammation is the most common milieu of IBD-related involvement, with bronchiectasis being the most common manifestation. Furthermore, significant differences in prevalence and types of involvement are present between Crohn's disease and ulcerative colitis. The same embryological origin of respiratory and gastrointestinal tissue, in addition to exposure to common antigens and cytokine networks, may all play a potential role in the respiratory involvement. Furthermore, other causes such as drug-related toxicity and infections must always be considered. This article aims at reviewing the current evidence on the association between IBD and respiratory diseases. The purpose is to raise awareness of respiratory manifestation among IBD specialists and emphasize the need for identifying respiratory diseases in early stages to promptly treat these conditions, avoid worsening morbidity, and prevent lung damage.

Patients with Crohn's disease (CD) are most often diagnosed as young adults; therefore, long-term studies are needed to assess the risk of cancer over their lifetime. Thus, the aims of the present study were to determine the risk of cancer in a Norwegian population-based cohort (the Inflammatory Bowel South Eastern Norway [IBSEN] study), 30 years after diagnosis, and to assess whether patients with CD were at an increased risk of specific cancer types.

The IBSEN cohort prospectively included all incident patients diagnosed between 1990 and 1993. Data on cancer incidence were obtained from the Cancer Registry of Norway. Overall and cancer-specific hazard ratios (HRs) for CD patients compared with age- and sex-matched controls were modeled using Cox regression. Standardized incidence ratios (SIRs) were estimated compared to the general population.

In total, the cohort included 237 patients with CD, and 36 of them were diagnosed with cancer. Compared to the general Norwegian population, patients with CD had an increased overall risk of cancer (HR = 1.56, 95% CI: 1.06-2.28), particularly male patients (HR = 1.85, 95% CI: 1.08-3.16). The incidence of lung cancer and nonmelanoma skin cancer was increased; however, the difference was not statistically significant (SIR = 2.29, 95% CI: 0.92-4.27 and SIR = 2.45, 95% CI: 0.67-5.37, respectively).

After 30 years of follow-up, the risk of all cancers in patients with CD was increased compared to the general population.

Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD.

Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first systematic review and meta-analysis evaluating the burden of anal human papillomavirus disease in patients with UC and CD.

PubMed, Web of Science, and Scopus were searched until November 2022. Meta-analyses were performed using random effects models. The protocol was recorded at PROSPERO register with the number CRD42022356728.

Six studies, including 78 711 patients with UC with a total follow-up of 518 969 person-years, described the anal cancer incidence rate. For anal cancer incidence rate in CD, six studies were selected, including 56 845 patients with a total follow-up of 671 899 person-years. The incidence of anal cancer was 10.2 [95% CI 4.3 - 23.7] per 100 000 person-years in UC and 7.7 [3.5 - 17.1] per 100 000 person-years in CD. A subgroup analysis of anal cancer in perianal CD, including 7105 patients, was calculated with incidence of 19.6 [12.2 - 31.6] per 100 000 person-years [three studies included]. Few studies described prevalence of anal cytological abnormalities [four studies including 349 patients] or high-risk human papillomavirus [three studies including 210 patients], with high heterogeneity. Prevalence of cytological abnormalities or high-risk human papillomavirus was not associated with pharmacological immunosuppression in the studies included.

The incidence of anal cancer is higher in UC than in CD, with the exception of perianal CD. There are limited and heterogeneous data on anal high-risk human papillomavirus infection and squamous intraepithelial lesions prevalence in this population.

There are limited data on the association between uterine cervical cancer (UCC) and inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC).

This systematic review and meta-analysis assessed the risk of UCC in patients with IBD. We searched MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, gray literature and conference proceedings for studies published before 21 January 2022. Two reviewers independently screened studies, extracted data and assessed quality using the Newcastle-Ottawa Scale. Subgroup analyses were based on IBD type, biologic era, immunosuppression status, study location and design, and publication status. Fifteen studies were included.

The pooled relative risk (RR) of UCC in IBD was 1.34 (95% confidence interval [CI], 1.07-1.69; I2 = 53.4%). In subgroup analyses, the pooled RRs of UCC in CD and UC were 1.18 (95% CI, 0.97-1.42) and 1.50 (95% CI, 1.01-12.21), respectively. The pooled RRs of UCC in pre-biologic and biologic eras were 1.36 (95% CI, 0.83-2.23) and 1.99 (95% CI, 1.03-3.86), respectively. The pooled RR of UCC in immunomodulator users was 2.18 (95% CI, 0.81-5.87). The pooled RRs of UCC in Asia, Europe and North America were 5.65 (95% CI, 2.65-12.07), 1.13 (95% CI, 0.96-1.34) and 1.38 (95% CI, 1.10-1.73), respectively.

The risk of UCC was significantly increased in IBD, particularly in UC but not in CD, suggesting that women with IBD should undergo regular UCC screening and consider vaccination.

Patients with ulcerative colitis (UC) have shown an increased risk for colorectal cancer, hepatobiliary, hematologic, and skin cancers, but updated long-term data is needed. This study aimed to estimate the risk of cancer in patients with UC compared to the general Norwegian population, in a population-based cohort (the IBSEN study), 30 years after diagnosis; and to identify possible risk factors associated with cancer.

The IBSEN cohort prospectively included all incident patients between 1990 and 1993. Cancer incidence data were obtained from the Cancer Registry of Norway. The overall and cancer-specific hazard ratios (HR) were modelled using Cox regression. Standardized incidence ratios were estimated compared to the general population.

In total, the cohort included 519 patients, and 83 cases were diagnosed with cancer. There was no statistically significant difference in the overall cancer risk (HR = 1.01, 95% CI: [0.79-1.29]) and colorectal cancer risk (HR = 1.37, 95% CI: [0.75-2.47]) between patients and controls. The incidence of biliary tract cancer was higher than expected (SIR = 9.84, 95%CI: [3.19-20.15]), especially when UC patients suffered from primary sclerosing cholangitis. Male UC patients were also more at risk of being diagnosed with hematologic malignancies (HR = 3.48, 95% CI: [1.55-7.82]). Being prescribed thiopurines was associated with a higher risk of cancer (HR = 2.03, 95% CI: [1.02-4.01]).

At 30 years after diagnosis, the risk of all cancer in patients with UC was not significantly increased compared with the general population. However, the risks of biliary tract cancer and hematologic cancers were increased, particularly in male patients.

Numerous observational studies have been conducted to investigate the potential association between inflammatory bowel disease (IBD) and prostate cancer (PCa). However, a definitive conclusion has yet to be established. We therefore performed a meta-analysis to explore the relationship between these two conditions.

PubMed, Embase, and Web of Science databases were systematically searched to identify all relevant cohort studies that investigated the association between IBD and risk of incident PCa published from inception to February 2023. The pooled hazard ratios (HRs) with 95% confidence intervals (CI) was calculated as effect size for the outcome based on random-effects model meta-analysis.

A total of 18 cohort studies with 592,853 participants were included. The meta-analysis revealed that IBD was linked to an elevated risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.37, P = 0.004). Further subgroup analyses revealed that ulcerative colitis (UC) was linked to an increased risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.38, P = 0.006), while Crohn's disease (CD) is not significantly associated with a higher risk of PCa (HR = 1.03, 95% CI: 0.91-1.17, P = 0.65). There was a significant correlation between IBD and an elevated risk of incident PCa in the European population, but such a correlation was not observed in the Asian and North American populations. Sensitivity analyses indicated that our results were robust.

Our latest evidence indicates that IBD was linked to an elevated risk of incident PCa, especially in UC patients and the European population.

Inflammatory bowel disease (IBD) is a chronic disease for which medical treatment with immunomodulating drugs is increasingly used earlier to prevent disability. Additionally, cancer occurrence in IBD patients is increased for several reasons, either IBD-related or therapy-associated. Doctors are therefore facing the challenge of managing patients with IBD and a past or current malignancy and the need to balance the risk of cancer recurrence associated with immunosuppressive drugs with the potential worsening of IBD activity if they are withdrawn. This review aims to explore the features of different subtypes of cancer occurring in IBD patients to present current evidence on malignancy recurrence risk associated with IBD medical therapy along with the effects of cancer treatment in IBD and finally to discuss current recommendations on the management of these patients. Due to sparse data, a case-by-case multidisciplinary discussion is advised, including inputs from the gastroenterologist, oncologist, and patient.

Both inflammatory bowel disease (IBD) and hepato-pancreato-biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC.

Herein, we utilized inverse-variance weighting to conduct a two-sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses.

Compared to the general population, IBD patients in Europe exhibited a 1.22-fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022-1.4888 (p = 0.0475). We also found a 1.14-fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017-1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28-fold higher (95% CI = 1.0709-1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12-fold (95% CI: 1.1466-1.3334, p < 0.0001) and 1.31-fold (95% CI: 1.0983-1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19-fold higher in CD patients than in the general population (95% CI = 1.0741-1.3132, p = 0.0008).

Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations.