Introduction: Clostridium septicum (C. septicum) is a virulent, spore-forming, gram-positive anaerobe that causes spontaneous gas gangrene and necrotizing fasciitis, even in the absence of trauma. In a review of 94 cases of gas gangrene due to C. septicum, an associated malignancy was identified in 71% of patients, 61.5% of which were gastrointestinal. Given its aggressive nature and poor prognosis, timely recognition and source control are essential. Description: A 60-year-old woman with type 2 diabetes (status post right below-knee amputation), chronic kidney disease, heart failure with preserved ejection fraction, peripheral vascular disease and prior pulmonary embolism presented with fever, nausea, vomiting, and confusion after a fall owing to hypotension, resulting in gluteal bruising. She was hypotensive (BP 74/45), tachycardic (HR 120), febrile (102.2°F) and tachypneic. Labs showed leukocytosis, anemia, elevated creatinine, hyperglycemia, lactic acidosis and an anion gap metabolic acidosis. Physical exam showed left gluteal tenderness and bruising. CT abdomen/pelvis revealed subcutaneous emphysema in the gluteus maximus and pancolitis. She received broad-spectrum antibiotics and underwent debridement revealing necrotic fascia and purulence. Blood cultures confirmed C. septicum bacteremia. Given the known malignancy association, further evaluation was pursued. Total abdominal colectomy revealed polypoid ileocecal mass, identified as tubulovillous adenoma with high-grade dysplasia. The patient was on vasopressors in the ICU for septic shock, subsequently stabilized and transferred to the floor on day 20. Discussion: C. septicum infections may present as cellulitis, fasciitis, visceral abscesses or spontaneous gas gangrene. Vague early symptoms often mimic other intra-abdominal conditions. Pathogenesis involves tumor-related mucosal disruption, bacterial translocation and a hypoxic, acidic environment favoring spore germination and toxin release. In our patient, rapid decline despite antibiotics and debridement prompted surgical evaluation, revealing underlying colonic neoplasia, highlighting the importance of considering gastrointestinal malignancy in patients with C. septicum bacteremia and emphasizing the need for early diagnosis, surgical intervention and appropriate antimicrobial therapy.

Abstract Background Managing active ulcerative colitis (UC) in solid organ transplant recipients is challenging due to complex multidrug regimens and higher risks of complications. We assessed the efficacy and safety of vedolizumab in UC patients after liver transplantation (LT) who failed conventional treatment and were naïve to advanced therapies. Methods This multicenter retrospective study included adult post-LT patients with moderately to severely active UC (Mayo score ≥6) who were naïve to advanced therapies and received vedolizumab 300 mg intravenously at weeks 0, 2, and 6. Week-14 treatment response, required for therapy reimbursement, was defined as a ≥ 30% and ≥3-point Mayo score reduction; remission as Mayo score ≤2. Endoscopic improvement required a Mayo endoscopic subscore of 0–1 with ≥1-point improvement. Data on maintenance therapy in responders and treatment-related complications were collected. The study was approved by the local Bioethics Committee. Results Twenty-nine eligible patients treated across 10 Polish gastroenterology centers between 2021 and 2025 were identified (20 males, 9 females; median age 33 years, range 19–54). Indications for liver transplantation included primary sclerosing cholangitis (PSC; 19 patients, with recurrent PSC diagnosed in 9), overlapping autoimmune hepatitis/PSC (AIH/PSC; 7 patients), and AIH (3 patients). The median interval since LT was 6 years (range 1–14), and the median duration of UC was 10 years (range 3–22); extensive UC was present in 23 patients. The median follow-up period was 9 months (range 1–47). At week 14, 24 patients (83%) achieved a clinical response and proceeded to intravenous or subcutaneous maintenance therapy. Clinical remission occurred in 6 patients (21%), and endoscopic improvement in 13 (45%). At the time of analysis, 14 patients (48%) remained on vedolizumab. Severe complications were the main reasons for discontinuation in 10 responders, including intestinal lymphoma (n = 1), colonic dysplasia (n = 1), cholangitis (n = 2), Epstein–Barr virus infection (n = 1), and Clostridioides difficile infection (n = 1). One patient experienced secondary loss of response; in two, infusion intervals were shortened for symptom worsening. Two patients stopped treatment voluntarily, and one died after a second LT. One patient had an uncomplicated pregnancy while continuing subcutaneous vedolizumab. Conclusion The 14-week clinical response rate to vedolizumab in UC patients after LT was high, with nearly half achieving endoscopic improvement. However, the modest remission rate indicates that longer treatment may be necessary to reach optimal targets in this population. Close surveillance remains crucial for early detection of UC/PSC-related and treatment-associated complications. Conflict of interest: Kucha, Piotr: Other: Support for attending meetings or travel from Takeda Zaborowska, Marta: Travel grant from Abbvie and Pfizer Wypych, Joanna: Received lecture fees, consultancy fees, or travel educational grants from Takeda, Eli Lilly, Abbvie, Recordati Augustyn, Monika: No conflict of interest Brodowski, Tomasz: No conflict of interest Eder, Piotr Michał: Travel and educational grants: Takeda, Ferring, Abbvie, Janssen (J&J), Eli Lilly. Lecture and/or consultancy fees: Takeda, Abbvie, Ferring, Janssen (J&J), Eli Lilly, Bristol Myers Squibb, Pfizer, Recordati, Ibsen, Sandoz. Filip, Rafal: No confict of interest to declare Gawron-Kiszka, Magdalena: Lecture fees and/or travel grants from AbbVie, Eli Lilly, Ferring, Janssen, Pfizer, Recordati, Sobi, Takeda Kaniewska, Magdalena: to be Koza, Jarosław: No conflict of interest Kłosowska-Kapica, Krystyna: No conflict of interest Maciejewska, Katarzyna: Received lecture fees, consultancy fees, or travel educational grants from Takeda, Abbvie, Eli Lilly, SOBI Zagórowicz, Edyta Sylwia: Honoraria for lectures: J&J, Takeda, Abbvie, Lilly. Advisory boards: J&J, Lilly. Travel grants: Takeda.

Inflammatory bowel disease (IBD) is an increasingly prevalent disease, affecting over seven million people worldwide and imposes a heavy burden on public health. The rising prevalence of IBD may be attributed to the hygiene hypothesis, which suggests that reduced exposure to parasites and microbes may weaken the immune system, thereby increasing susceptibility to developing IBD. Studies suggest helminths and their secretory products can modulate the host immunity and attenuate IBD. Our previous research also demonstrated that intestinal schistosomiasis can mitigate chronic IBD symptoms by restoring intestinal immune balance and dysbiosis. While the primary pathology of schistosomiasis results from egg entrapment, we hypothesised that soluble egg antigen (SEA), known for its strong immunomodulatory effect, may contribute to the improvement of IBD. Given that SEA comprises multiple different proteins, identifying the role of individual components may clarify the therapeutic potential of SEA in IBD. BALB/c mice were induced with dextran sodium sulphate (DSS) to develop IBD. Throughout the experiment, mice were intraperitoneally injected with 250 μg/mL crude SEA extract or recombinant egg antigen proteins, including SM14, GST28, and SMP40, three times a week. Colonic histopathology was assessed by H&E staining, and the immune response was evaluated through periodic acid-Schiff (PAS) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), western blot, and quantitative polymerase chain reaction (qPCR). Both SEA and Smp40 alleviated DSS-induced IBD, whereas SM14 exacerbated the disease and led to colonic dysplasia. In contrast, GST28 showed no significant effect on IBD. Further investigation revealed that all tested proteins modulated the immune response in mice, though each did so in different ways. These differences in immune modulation may underlie the varying disease outcomes observed. While SEA has shown therapeutic promise in IBD, it is also important to investigate the safety and mechanisms of individual antigens before considering their clinical application in the future.

Introduction: Patients with Ulcerative colitis (UC) and Crohn’s colitis (CC) are at an increased risk of developing colorectal cancer (CRC). In a 2021 clinical practice update, the American Gastroenterological Association (AGA) recommends surveillance colonoscopy at varying intervals (1, 2-3, or 5 years) to assess for colonic dysplasia or CRC. The recommended interval depends on risk factors such as medical/family history, extent of inflammation, and history of dysplasia. This study evaluated adherence to these guidelines at Westchester Medical Center (WMC). Methods: A retrospective chart review was conducted for patients aged ≥18 years with UC or CC who received a colonoscopy for dysplasia/CRC surveillance between October 2021 and July 2024. Patients were eligible if they were diagnosed ≥8 years prior to colonoscopy, or at the time of diagnosis if they also had primary sclerosing cholangitis (PSC). All procedures were performed with high-resolution colonoscopes, with both targeted and random biopsies. Endoscopic, histologic, laboratory, and historical data were collected. The recommended surveillance interval was assessed based on AGA guidelines and was compared to the interval documented on the endoscopy report. Descriptive statistics were used for analysis. Results: Of 311 charts reviewed, 113 met inclusion criteria. Sixty-three were men (56%). Ages ranged from 20 to 83 (median 51). Fifty-four were diagnosed with UC (48%) and 57 with CC (50%). Twelve had PSC (11%), 7 had history of colonic dysplasia (6%), and 6 had first degree relative with CRC history (5%). On colonoscopy, 15 had evidence of moderate/severe mucosal inflammation (13%), 5 had dense pseudopolyps (4%), and 24 had mucosal scarring (21%). On histology, 35 had active inflammation (31%) and 1 had dysplasia (1%). Seventy patients (62%) had a documented surveillance interval for next colonoscopy; of these, 43 were concordant with the AGA guideline (61%). Among discordant cases, 26 were recommended a repeat colonoscopy earlier than the AGA guideline recommends (96%). Conclusion: Our findings demonstrate suboptimal documentation and adherence to AGA-recommended surveillance intervals for patients with UC and CC undergoing CRC surveillance at WMC. When documented on endoscopy reports, surveillance intervals were often shorter than AGA guideline recommendations, potentially leading to unnecessary procedures and increased resource utilization. We propose targeted interventions such as EMR-based prompts and educational outreach to improve adherence to AGA guidelines.

BackgroundChronic stress and gut dysbiosis are established risk factors for colorectal adenocarcinoma, yet their synergistic effects on the development of intestinal precancerous lesions remain poorly understood.MethodsThis study investigates the molecular mechanisms through which chronic stress interacts with opportunistic pathogen Listeria monocytogenes to drive intestinal tumorigenesis in ApcMin/+ mice, with particular focus on the involvement of tumor immune microenvironment remodeling.ResultsThe combination of L. monocytogenes infection and chronic stress, rather than bacterial infection alone, significantly increased colonic adenoma burden and epithelial dysplasia, suggesting that chronic stress establishes a permissive microenvironment for opportunistic pathogens to exert pro-tumorigenic effects. Mechanistically, chronic stress downregulated intestinal epithelial Muc-2 expression and reduced microbial diversity, thereby compromising mucus/microbial barrier integrity and enhancing L. monocytogenes colonization. Under dual stress-pathogen exposure, we observed the expansion of myeloid-derived suppressor cells (MDSCs) in spleen and the upregulation of IL-6 in colonic mucosa, which facilitated MDSCs recruitment to tumor sites. Infiltrating MDSCs driven CD8+ T cell depletion through cAMP/PKA/CREB signaling, leading to the establishment of immunosuppressive microenvironment.ConclusionOur results propose that chronic stress-induced gut barrier disruption may serve as a prerequisite for opportunistic pathogens to accelerate the development of precancerous lesions. Their synergistic effects reshape systemic/local immune responses, creating a microenvironment conducive to malignant transformation and tumor cell survival. These preliminary findings highlight potential clinical applications of psychological interventions and immune modulation strategies in preventing intestinal carcinogenesis.

This study reveals a distinct metagenomic, metabolomic, and lipidomic profile associated with tumorigenesis in a murine model of ulcerative colitis, highlighting the risks of specific intestinal dysbiosis in genetically predisposed subjects. Background and context: Colitis-associated colorectal cancer arises from complex host-environment interactions, including gut microbiome influences, driving chronic inflammation, with the intestinal lumen environment remaining a largely unexplored potential risk factor in cancer development.New findings: Winnie mice in specific pathogen-free conditions developed severe colitis, and a novel juvenile colon dysplasia and cancer, with gut microbiome changes driving colitis-associated cancer initiation and progression.Limitations: We identified a pro-inflammatory microbial/metabolic signature promoting colitis-to-CAC transition in Winnie mice, with FMT confirming microbiota-driven tumor susceptibility. However, further research is needed to pinpoint the key bacteria-metabolite-lipid combination driving CAC.Clinical research relevance: This newly characterized microbiota-metabolome-based model of CAC, challenges the dogma of cancer as a non-transmittable disease, providing a foundation for developing microbiota-based strategies for CAC prevention and treatment.Basic research relevance: Unlike genetic or chemically induced models, the Winnie mouse model uniquely serves as a dual model for spontaneous colitis and juvenile CAC, offering a fast, 100% penetrant phenotype that enhances reliability, accelerates research, and provides valuable insights into IBD and CAC.

Liver Transplant is Associated with a Reduced Risk of Colorectal Dysplasia in patients with IBD and concomitant PSC

Sa1221: DELETED IN MALIGNANT BRAIN TUMORS 1 (DMBT1) GLYCOPROTEIN IS LOST IN COLONIC DYSPLASIA

In the general population, right I-sided dysplasia presents a higher risk for colorectal cancer (CRC) and metachronous dysplasia compared to left (L)-sided dysplasia. Given that patients with inflammatory bowel disease (IBD) are at higher risk for dysplasia than the general population, we sought to assess the risk factors as well as the differences in outcomes between patients with R-sided, L-sided, and both R- and L-sided dysplasia. A retrospective chart review was performed on patients at NYU Langone Health who had evidence of dysplasia on a colonoscopy between 2011 and 2021. Demographics and pertinent medical history were compiled. Cohorts were based on the dysplasia location (R-sided, L-sided, or R- and L-sided) and the IBD-related outcomes were analyzed. A total of 71 patients had colonic dysplasia. The mean age was 54 years old (SD ± 17). The majority were male (72%), white (69%), and non-Hispanic (94%). A total of 76% had ulcerative colitis (UC) and 24% had Crohn's disease (CD). Of all dysplastic lesions, 57 (80%) patients had unifocal disease and the remainder had multifocal disease. A total of 39 (55%) patients had R-sided dysplasia, 24 (34%) had L-sided dysplasia, and 8 (11%) had both R- and L-sided dysplasia. Patients with UC were more likely to have L-sided dysplasia (92% vs. 8% in CD; p = 0.04). Pseudopolyps were more likely associated with R- and L-sided dysplasia (38% in R- and L-sided dysplasia, 10% in R-sided dysplasia, and 4% in L-sided dysplasia; p = 0.03). Patients with UC had a higher risk for L-sided colonic dysplasia compared to patients with CD; however, there were no differences in the progression of dysplasia between those who had R-sided and those who had L-sided dysplasia. Larger studies are needed to assess the risk factors and outcomes related to the laterality of dysplasia and further validate these findings among patients with IBD.

Single-port laparoscopic assisted ileal vaginal replacement for the management of Cloaca: A Novel approach.

PurposeThe existing data on colon lesions in acromegaly is notably heterogeneous. This study aimed to analyze the endoscopic and histopathological characteristics of colon polyps and other colonic lesions in acromegaly patients.MethodsThis case-control study included 192 acromegaly patients and 256 controls. Colon polyps were categorized based on their size and histopathological classification. Colon malignancies and other colonic lesions, such as anal fissures, hemorrhoids, and diverticulosis, were also documented.ResultsThe prevalence of colon polyps was higher in the acromegaly group than in controls (p = 0.003), however, no differences were observed in the number, size, or histopathological subtypes of the polyps. Polyps in acromegaly patients were predominantly located in the distal colon and rectum. Multiple polyp locations and histopathological subtypes were more frequent in the control group (p = 0.042 and p = 0.018). Rates of low-grade dysplasia, high-grade dysplasia, and malignancy were similar between groups. Anal fissures were more common in the acromegaly group, whereas diverticulosis was less frequent (p = 0.001 and p < 0.001; respectively). Logistic regression analysis identified no significant clinical or laboratory predictors for colon polyps in acromegaly.ConclusionPatients with acromegaly exhibited a higher prevalence of colon polyps, predominantly located in the distal colon, which typically displayed a single histopathological subtype. No increased rates of colonic dysplasia, colon cancer, or other colonic lesions were observed in patients with acromegaly, except for an elevated prevalence of anal fissures.

Colorectal cancer (CRC) is responsible for over 900,000 annual deaths worldwide. Emerging evidence supports pro-carcinogenic bacteria in the colonic microbiome are at least promotional in CRC development and may be causal. We previously showed toxigenic C. difficile from human CRC-associated bacterial biofilms accelerates tumorigenesis in ApcMin/+ mice, both in specific pathogen-free mice and in gnotobiotic mice colonized with a defined consortium of bacteria. To further understand host-microbe interactions during colonic tumorigenesis, we combined single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and immunofluorescence to define the molecular spatial organization of colonic dysplasia in our consortium model with or without C. difficile. Our data show a striking bipartite regulation of Deleted in Malignant Brain Tumors 1 (DMBT1) in the inflamed versus dysplastic colon. From scRNA-seq, differential gene expression analysis of normal absorptive colonocytes at 2 weeks post-inoculation showed DMBT1 upregulated by C. difficile compared to colonocytes from mice without C. difficile exposure. In contrast, our spatial transcriptomic analysis showed DMBT1 dramatically downregulated in dysplastic foci compared with normal-adjacent tissue. We further integrated our datasets to generate custom colonic dysplasia scores and ligand-receptor mapping. Validation with immunofluorescence showed DMBT1 protein downregulated in dysplastic foci from three mouse models of colonic tumorigenesis and in adenomatous dysplasia from human samples. Finally, we used mouse and human organoids to implicate WNT signaling in the downregulation of DMBT1 mRNA and protein. Together, our data reveal cell type-specific regulation of DMBT1, a potential mechanistic link between bacteria and colonic tumorigenesis.

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.

Abstract Background Long-standing inflammation has been implicated in the development of colonic dysplasia in ulcerative colitis (UC). However, the relationship between varying degrees of inflammatory exposure and dysplasia risk remains poorly understood. We aimed to identify risk factors for colonic dysplasia in UC patients, with particular focus on quantifying long-term inflammatory exposure. Methods In this retrospective single-center case-control study, we reviewed 55 UC patients diagnosed with colonic dysplasia (low-grade, high-grade, or cancer) between 2013 and 2022, and 110 randomly selected UC patients without dysplasia as controls. Endoscopic inflammation was scored using the Mayo endoscopic subscore (0-3), and cumulative inflammatory exposure was calculated by multiplying these scores with the duration of each endoscopic follow-up period. Clinical factors and endoscopic findings were compared between groups, and logistic regression analysis was performed to identify independent predictors of dysplasia. Results Univariate analysis showed that the dysplasia group had significantly higher frequencies of anemia (hemoglobin &amp;lt;10 g/dL), elevated ESR (&amp;gt;18 mm/hr at diagnosis), steroid and biologics use, tubular or shortened colon, and high cumulative endoscopic inflammation scores (&amp;gt;10). In multivariate analysis, after adjusting for age, gender, and disease duration, both tubular or shortened colon (OR 3.172, 95% CI: 1.029-9.780) and high cumulative endoscopic inflammation score(&amp;gt;10) (OR 4.205, 95% CI: 1.065-16.600) were independently associated with increased dysplasia risk. Conclusion High cumulative inflammatory burden, as indicated by elevated endoscopic inflammation scores and structural bowel changes, significantly increases the risk of colonic dysplasia in UC patients. More intensive surveillance strategies may be warranted for patients with these objective risk indicators to enable early detection of colitis-associated dysplasia.

Abstract Background Colonic high-grade dysplasia (HGD) is the highest-risk precursor of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients with reported incidence rates of 1.0-3.5%.1-4 Data on metachronous CRC risk after HGD in IBD are limited and outdated. The aim of this study was to determine the long-term risk of CRC and colorectal neoplasia (including indefinite for dysplasia, low-grade dysplasia, HGD and CRC) after a first diagnosis of HGD in IBD, and to assess HGD treatment strategies. Methods In this nationwide retrospective cohort study, patients with both a colonic IBD and HGD diagnosis between 1991 and 2021 were extracted from the Dutch nationwide pathology databank (PALGA). The primary outcome was the cumulative incidence of metachronous CRC and colorectal neoplasia. Cox proportional hazard models were used to assess associations with metachronous CRC. Kaplan Meier curves were used to show proctocolectomy free survival per decade. Results CRC was diagnosed in 358 of 1,223 patients with HGD (29.3%) after a median 0.3 years (IQR 0.1-2.7, figure 1). Of these, 203 patients (16.6%) were diagnosed with CRC within 6 months after the first HGD diagnosis and were considered synchronous CRC patients. Metachronous CRC was diagnosed in 155 of 1,020 patients (15.2%) after a median 4.1 years (IQR 1.3-11.0). The 1-, 5-, and 10-year cumulative incidences of metachronous CRC after HGD were 2.9%, 10.4%, and 17.2%, respectively. After a median of 2.2 years (IQR 1.0-5.7), 642 patients (62.9%) developed metachronous colorectal neoplasia (indefinite for dysplasia as highest grade: n=12 [1.9%]; low-grade dysplasia: n=243 [37.9%]; HGD: n=220 [34.3%]; CRC: n=155 [24.1%], figure 1). The 1-, 5- and 10-year cumulative incidences of metachronous colorectal neoplasia were 18.0%, 53.9% and 75.0%, respectively. Post-inflammatory polyps (aHR 1.88, 95% CI 1.33-2.65, p&amp;lt;0.01), strictures (aHR 1.62, 95% CI 1.02-2.58, p=0.04), invisible index HGD (aHR 2.04, 95% CI 1.24-3.35, p&amp;lt;0.01), academic follow-up (aHR 1.54, 95% CI 1.10-2.17, p=0.01), and endoscopic vs. surgical treatment (aHR 2.31, 95% CI 1.17-4.57, p=0.02) were associated with metachronous CRC. Proctocolectomy was performed in 209 (17.1%) patients after a median 4.7 years (IQR 1.5-9.7) after index HGD diagnosis. Proctocolectomy free survival did not differ between decades of HGD diagnosis after 8 years of follow-up (p=0.58). Conclusion The high cumulative incidence of synchronous and metachronous CRC after a diagnosis of HGD underlines the high-risk profile for this subgroup of IBD patients. The possible advantages of colon sparing treatment for HGD should be balanced with the subsequent higher risk of metachronous CRC and colorectal neoplasia and resulting need for stringent endoscopic surveillance.

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.

BackgroundInflammatory bowel disease increases the risk of colorectal neoplasia. A particular problem arises in patients who have undergone subtotal colectomy leaving a rectal remnant. The risk of future rectal cancer must be accurately estimated and weighed against the risks of further surgery or surveillance. The aim of this study was to estimate the 10-year cumulative incidence of rectal cancer in such patients.MethodsA nationwide study using England’s hospital administrative data was performed. A cohort of patients undergoing subtotal colectomy between April 2002 and March 2014 was identified. A competing risks survival analysis was performed to calculate the cumulative incidence of rectal cancer. The effect of the COVID-19 pandemic on endoscopic surveillance was investigated using time-trend analysis.ResultsA total of 8120 patients were included and 61 patients (0.8%) were diagnosed with cancer. The cumulative incidence of rectal cancer was 0.26% (95% c.i. 0.17% to 0.39%), 0.49% (95% c.i. 0.36% to 0.68%), and 0.77% (95% c.i. 0.57% to 1.02%) at 5, 10, and 15 years respectively. A previous diagnosis of colonic dysplasia (HR 3.34, 95% c.i. 1.01 to 10.97; P = 0.047), primary sclerosing cholangitis (HR 5.42, 95% c.i. 1.34 to 21.85; P = 0.018), and elective colectomy (HR 1.83, 95% c.i. 1.11 to 3.02; P = 0.018) was associated with an increased incidence of rectal cancer. Regarding endoscopic surveillance, there was a 43% decline in endoscopic procedures performed in 2020 (333 procedures) compared with 2019 (585 procedures).ConclusionThe incidence of rectal cancer after subtotal colectomy is low. Asymptomatic patients without evidence of rectal dysplasia should be carefully counselled on the possible benefits and risks of prophylactic proctectomy.

Artificial intelligence for dysplasia detection during surveillance colonoscopy in patients with ulcerative colitis: A cross-sectional, non-inferiority, diagnostic test comparison study

Abstract Colorectal cancer (CRC) is the third most common cancer in the United States and is responsible for more than 50,000 deaths annually. Emerging evidence strongly supports a causal role for specific pro-carcinogenic driver bacteria within the colonic microbiota. Invasive bacterial biofilms may initiate or accelerate CRC through epithelium-autonomous or inflammation-dependent mechanisms. To better understand host-microbe interactions during colonic tumorigenesis, we combined single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and immunofluorescence to define the molecular spatial organization of colonic tissue from germ-free ApcMin/+ mice colonized with bacteria from human biofilm-associated CRC. In absorptive colonocytes, differential gene expression analysis showed the gastric metaplasia-associated glycoprotein Deleted in Malignant Brain Tumors 1 (DMBT1) is highly upregulated by C. difficile. Surprisingly, our spatial transcriptomic analysis showed DMBT1 was dramatically downregulated in dysplastic foci compared with normal-appearing tissue. We show that DMBT1 protein is downregulated in 100% of dysplastic foci across 3 different mouse models of colonic tumorigenesis: C. difficile-associated tumorigenesis in ApcMin/+, azoxymethane/dextran sodium sulfate, and Lrig1CreER/+;Apcfl/+ mice (n = 57 foci from 11 mice). Immunofluorescent staining of DMBT1 is markedly downregulated compared with normal adjacent crypts. Using scRNA-seq data and tissue microscopy in human CRC, we confirmed the same pattern of downregulated DMBT1 expression in dysplastic crypts compared with normal-appearing crypts. We present data from a human mucosal biofilm-associated colonic tumorigenesis murine model at single-cell resolution to reveal interesting cell type-specific transitions and generalizable mechanisms of tumorigenesis. We hypothesize that DMBT1 is a component of the gut epithelial response to pathogens and a critical regulator of proliferation and differentiation during post-injury restitution. We are now functionally testing how the loss of DMBT1 impacts tumorigenesis using human organoids. Ultimately, these studies aim to reveal novel biomarkers and/or targets for therapeutic intervention in CRC. Citation Format: Emily H. Green, Subhag R. Kotrannavar, Megan E. Rutherford, Harsimran Kaur, Hannah M. Lunnemann, Cody N. Heiser, Shaoguang Wu, Hua Ding, J. Alan Simmons, Xiao Liu, D. Borden Lacy, Martha J. Shrubsole, Qi Liu, Ken S. Lau, Cynthia L. Sears, Robert J. Coffey, Julia L. Drewes, Nicholas O. Markham. Deleted in malignant brain tumors 1 (DMBT1) glycoprotein is lost in colonic dysplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6693.

Setting up an integrated service for PSC-IBD patients: A quality improvement project