Colonic Location Research Articles

P287 Clinical characteristics and outcomes of ileal pouch–anal anastomosis (IPAA) inflammation in a Latin American (LA) IBD reference Center (I.

Abstract Background Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) can be associated with a wide spectrum of complications, ranging from a frequently mild acute pouchitis (AP) to Chronic pouch inflammation (CPI, either antibiotic dependent or refractory, CADP and CARP respectively) and Crohn's disease like pouch inflammation (CDLPI). The pathogenesis, still largely unknown, probably is multifactorial, and environment may play a role. We aimed to describe clinical characteristics and outcomes of IPAA inflammation in a Latin American (LA) IBD reference Center. Our main focus is CDLPI, because, despite of UC is reported more frequent in LA, epidemiology is changing, and notably, colon location (within CD) reach the half of the CD casuistic in our hospital, as well as other Argentina locations (Cordoba) and Uruguay, a neighbor Country. Probably, this epidemiological feature could impact in our patient′s evolution. Methods Our hospital has a Coloproctology Team pioneer of IPAA surgery in Argentine and as Clinical IBD Service, we performed a revision in our electronic data base (included from 1990 to current date, and detected 437 pts. with IPAA. Criteria were; modified PDAI (for disease activity), for CPI and CDLPI we adopted that of Shen B, Clin. Gastrienterol hepatol 200, 6:145-58. Results Results We compare 46 CDLPI with 24 CPI pts. (CADP and CARP) and 24 AP. A total of 55 M, 39 F, were evaluated for demographic data and disease complications. Mean age ±SD at complication: CDLPI 33.8±13.8, CPI 34.2±11.2, AP 40.1±13.7, (NS for gender and Age). Median time (IQR) up to each one of 3 complications: 1.6 (4.19), 2.09 (7.17) and 1.34 (2.67), respectively (NS, Median test). Follow–up time was similar: 20.11 (10.9), 13.7 (12.2), 13.9 (15.6), respectively. CDLPI presented inflammatory pattern in: 37 (80.4%), stricturing in 6 (13.04%), fistulizing in 16 (34.8%) Perianal complication: 43.5%. Pre-pouch ileitis in CDLP: 26 (56 5%) vs. CPI 1(4.2%), in AP 0% (p.00000), prepouch strictures (13.04% vs. 0%), significant different, as well as prepouch fistulas (17.4%), with suboclusion in 29% Pouch vaginal fistulas and pouch-cutaneous in 1/5 of patients. Cuffitis in 19%. The original IBD was more severe and extensive p <0.02 in the mentioned subgroup. As regard treatment, IMM treatment in CDLP: was required in 70% vs. 26% in CPI and biologics en 2/3 0.00016, 11% ≥2 biologics. Pouch failure (diversion and resection) was observed in 30% and 13% respectively. Conclusion We are a LA center with high CD prevalence. The complications of surgery must be taken into account. IPAA revolutionized UC surgery, but close monitoring, and new research are required with the future hope of acting proactively.

P207 Colonic location at diagnosis of pediatric-onset Crohn’s disease is associated with a pejorative disease course: a two decades population-based study

Abstract Background Crohn's disease (CD) location would influence the risk of complications and therapeutic strategies. The objective of this study was to compare the clinical presentation at diagnosis and the natural history of colonic CD in comparison to ileal CD and ulcerative colitis (UC) in pediatric-onset inflammatory bowel disease. Methods All children (< 17 years) with a diagnosis of CD or UC made between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. Presentation at diagnosis, risks of complicated disease, surgery, hospitalization and exposure to treatments in ileal CD (L1), colonic CD (L2) and UC were compared. Disease location was defined at diagnosis. In case of extension of the disease (L1 or L2 to L3), follow-up was censored. Results A total of 215 L1 patients, 234 L2 patients and 337 UC patients were included. At diagnosis, the proportion of males (L1 53.5%; L2 53.4%; UC 42.7%; p=0.012), age at diagnosis (15.0; 13.7; 14.0 years; p=0.003), family history of IBD (12.6%; 12.7%; 5.0%; p=0.005), diagnostic delay (3.0; 3.0; 2.0 months; p=0.001) and smoking prevalence (11.6%; 8.1%; 5.6%; p=0.041) were different between the three groups. Bloody stool and diarrhea at diagnosis was observed in respectively 14.9%, 44.4%, and 91.1% (p < 0.001) and 47.0%, 71.8%, and 65.0% (p < 0.001) of L1, L2 and UC. At diagnosis, granuloma was identified in 12.6% of L1 patients and 31.2% of L2 patients (p<0.001). The risk of extension to L3 was significantly higher in the L2 group than in the L1 group (at 5 years - 37% vs. 14%, p<0.001). Compared to L1 location, L2 was associated with a lower risk of luminal fistula (HR 0.41 [0.21-0.79], p=0.008) but a higher risk of anoperineal lesion (HR 2.11 [1.29-3.45], p=0.003). The prevalence of extra-intestinal manifestations, articular (p<0.001) and cutaneous (p<0.001) was higher in L2. While the risk of surgery was significantly higher in case of L1 (at 5 years – L1 37%, L2 13% and UC 13%; p<0.001), the risk of hospitalization (at 5 years - 22%, 39% and 33%; p=0.01), exposure to corticosteroids (at 5 years - 55%, 69% and 67%; p<0.001), immunosuppressants (at 5 years - 47%, 61% and 42% - p<0.001) and anti-TNF (at 5 years - 16%, 35% and 22%; p<0.001) were higher in case of L2. Conclusion The clinical presentation at diagnosis and natural history of ileal and colonic CD differ significantly. Colonic location is associated with a high risk of perianal CD, extra-intestinal manifestations, hospitalization as well as exposure to steroids, immunosuppressants and anti-TNF. These differences may justify different therapeutic strategies in the future.

P155 Natural history of anal stricture in pediatric-onset Crohn’s disease: a two-decades population-based study

Abstract Background The natural history of anal stricture complicating pediatric-onset Crohn’s disease (CD) is poorly known. The aims of this study were: to determine in a population-based study the risk of anal stricture in pediatric-onset CD; to identify risk factors for anal stricture; and to evaluate the natural history of anal stricture at the population level. Methods All patients with a diagnosis of CD made before the age of 17 years between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. A specific collection of additional data was performed in patients with anal stricture at diagnosis or during follow-up. Variables collected included: proctological examination, diagnostic management and treatment. Multivariate Cox models were used to identify factors associated with anal stricture. Results Among the 1,007 included CD patients (females, 451 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0-16.1), median follow-up 8.8 years (IQR, 4.6-14.2)), only one (0.1%) had anal stricture at diagnosis while 26 (2.6%) presented anal stricture during follow-up. Cumulative incidence of anal stricture at 5 and 10 years after diagnosis was 0.6% (CI95%, 0.1-1.1) and 1.4% (CI95%, 0.5-2.3), respectively. Among the 27 patients with anal stricture, 25 (92.6%) had already at least one episode of anal ulceration or fistulizing perianal CD (pCD). In multivariable analysis, the presence of extra-intestinal manifestations (Hazard Ratio (HR) 2.2, CI95% 1.0-4.8, p=0.027), colonic location (L1 vs L3 HR 0.0 (-); L2 vs L3 HR 1.2, CI95% 0.6-2.7, p=0.006) and history of fistulizing pCD (HR 9.9, CI95% 4.3-22.8, p<0.0001) were significantly associated with anal stricture. Eleven (41%) patients needed at least one dilation. After a median follow-up of 16.9 years (IQR, 11.5-20.2), healing of anal stricture was observed only once. One patient (3.7%) presented an anal cancer 7 years after the diagnosis of anal stricture. Nine (33.3%) patients needed a stoma. Among them, 8 already had a fistulizing pCD and 4 needed an abdominoperineal amputation. Anal stricture was significantly associated with an increased risk of stoma (HR 5.8, CI95% 2.3-14.3), p=0.0002). Conclusion Anal stricture is a rare event in pediatric onset CD, occurring in 1.5% of patients over a 10 year-period after diagnosis. However, anal stricture had a negative impact on disease prognosis with a five-fold increase of the risk of stoma.

P293 Correlation between clinical measures to capture disease burden and prediction of the initial course of Crohn’s disease - findings from a Copenhagen IBD Inception Cohort Study (IBD Prognosis Study)

Abstract Background The initial disease burden of Crohn’s disease (CD) is dissimilar across patients; however, the ability to capture and predict the disease burden at diagnosis is scarcely investigated. The aim of the current study was to describe the initial disease burden of Crohn’s disease. Methods IBD Prognosis Study is an ongoing prospective population-based inception cohort of newly diagnosed patients with CD between May 1st, 2021, and November 1st, 2022, according to the Copenhagen IBD Criteria.1 We defined an indolent disease presentation as no need for CD-related surgery, hospitalization, nor initiation of steroid, immunomodulatory, or biologic therapies within the first 30 days after diagnosis, while a complicated course was defined as the opposite. Results The study included 134 patients with adult-onset CD, of whom approximately one-third (44/134, 33%) had an early indolent course, with 26 patients (19%) not requiring any medication (Tables 1-2). In demographic factor adjusted analyses, a colonic phenotype (adjusted odds ratio (aOR) =4.5 (95% confidence interval (CI) 1.6-15) and a low symptom load measured with Harvey-Bradshaw Index (HBI) <5 (aOR = 3.1 (CI 1.0-10) were independently associated with an indolent course. In contrast, a C-reactive protein (CRP) level higher than 10 mg/L was the only parameter associated with a complicated onset of CD (aOR = 4.7 (CI 2.1-12)). Pearson’s correlation analyses demonstrated a significant, moderate correlation between fecal (F-) calprotectin, CRP, and endoscopic lesions, measured with Simple Endoscopic Score for CD (SES-CD) (Table 3). HBI and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) exhibited a significant but weak correlation with CRP. In a sensitivity analysis allowing exposure to anti-inflammatory therapy for only up to seven days, the platelet count, F-calprotectin, and bowel wall thickness measured in IBUS-SAS demonstrated a significant and moderate correlation with SES-CD. The total IBUS-SAS and CRP showed a significant but weak correlation, and other measures included in the IBUS-SAS did not yield significant correlations. Conclusion Preliminary data from the ongoing population-based cohort indicate that one-third of patients with newly diagnosed CD have an early indolent course. This study identified colonic disease location and CRP levels to be associated with the early course, while platelet count, bowel wall thickness, and CRP were correlated with endoscopic lesions at the onset of CD.

Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases.

The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.

Abstract PR005: Features and susceptibility to dietary-induced alkylating damage in colorectal cancer

Abstract Introduction: Colorectal cancer (CRC) has several established risk factors, including diet. However, their mutagenic effect has not been observed directly in patients’ tumors and the individuals or ethnic groups who are most susceptible to diet-induced carcinogenesis are yet to be identified. We hypothesized that mutational signature analyses in CRC, coupled with epidemiologic, tumor molecular and patient germline data, can be linked to pre-diagnosis diet and specific germline alterations which can further inform cancer prevention efforts. Methods: We analyzed 900 CRCs with whole-exome sequencing (WES) and prospectively collected pre-diagnosis dietary data from the Nurses’ Health Studies I and II (NHS) and the Health Professionals Follow-up Study (HPFS), as well as 540 The Cancer Genome Atlas (TCGA) tumors and 295 non-Western CRCs from the Pan-Cancer Analysis of Whole Genomes. We additionally examined a sequencing dataset of normal colonic crypts. Following variant calling, mutational signature analyses were performed on cancer specimens using Non-negative Matrix Factorization. We leveraged the WES results to identify all patients that harbored the O-6-Methylguanine-DNA Methyltransferase (MGMT) germline rs16906252 single-nucleotide polymorphism (SNP), which is associated with tumor MGMT promoter hypermethylation and impaired alkylating damage repair. Results: We identified a novel alkylating mutational signature in CRC, which was associated with pre-diagnosis intake of red meats (overall red meat P = 0.017, unprocessed red meat P = 7.8×10-3, processed red meat P = 7.1×10-3, Mann-Whitney test), distal tumor location (P = 1.4×10-4, Mann-Whitney test) and worse CRC-specific survival (P trend = 0.036, multivariable Cox regression). We found a similar mutational signature in normal colonic crypts, suggesting an early oncogenic process. We showed that the alkylating signature’s oncogenicity is mainly mediated by KRAS p.G12D and KRAS p.G13D hotspot mutations. In addition, individuals harboring the MGMT rs16906252 germline SNP had a significant enrichment in tumors with alkylating damage (P = 0.015, Mann-Whitney test) and the effect of the SNP was synergistic with pre-diagnosis red-meat intake (P = 0.0099, Wald Test). Notably, we did not observe the alkylating mutational signature in CRCs from African and East-Asian patients, populations in which the MGMT rs16906252 SNP is largely absent. Conclusions: Through the integration of molecular and epidemiologic data, we identified evidence of red meat-associated alkylating damage in CRCs. This alkylating mutational signature was associated with distal colon location, KRAS oncogenic drivers, and poor CRC-specific survival. In addition, tumor alkylating damage was enriched among individuals harboring the MGMT germline rs16906252 polymorphism, absent in East Asian and African CRC patients and was synergistic with pre-diagnosis red-meat intake. Together, these results have significant implications for dietary-induced carcinogenesis and precision prevention in CRC. Citation Format: Carino Gurjao, Rong Zhong, Koichiro Haruki, Chichun Tan, Yvonne Li, Henry Lee-Six, Brendan Reardon, Tomotaka Ugai, Mingyang Song, Eliezer M. Van Allen, Charles S. Fuchs, Jonathan A. Nowak, Kana Wu, Jeffrey A. Meyerhardt, Edward L. Giovannucci, Jeffrey P. Townsend, Shuji Ogino, Marios Giannakis. Features and susceptibility to dietary-induced alkylating damage in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr PR005.

Changes in incidence and clinical features of inflammatory bowel disease in Cardiff, UK over 50 years: an update for 2005–2016

Introduction Population-based studies of inflammatory bowel disease (IBD) in Cardiff have recorded data back to 1930 for Crohn’s disease (CD) and 1968 for ulcerative colitis (UC). This study compares incidence and phenotype for 2005–2016 with past data. Methods All new IBD cases resident in the Cardiff at diagnosis were collected retrospectively for the 12-year period 2005–2016, and compared with previous Cardiff data for trends in incidence and phenotype. Overall incidence was age/sex corrected to the UK population. Results There were 991 new patients: 34% had CD, 5.4% IBD unclassified (IBD-U) and 60.5% had UC. The corrected incidence of CD was 7.7 per 100,000 person years [95% CI 6.9–8.6]. CD incidence is significantly higher than previous Cardiff studies, but the annual percentage change (APC) for 1980–2016 of 0.06; [95%CI −0.02 to 0.14] is not significant, with a previous higher APC for 1953–1980 of 0.18, [95%CI 0.13 to 0.23]. Uncorrected IBD-U incidence was 1.3 per 100,000 person years [95% CI 1.0–1.7]. UC corrected incidence was 14.4 per 100,000 person years [95% CI 13.3–15.6]. Incidence of UC is greater than in previous studies but did not increase during the current 12-year period. CD distribution at diagnosis continues to change as in previous Cardiff studies, with further increase in colonic disease and ileocolonic, (42% L2, 28% L3) and reduction in isolated terminal ileal disease (29% L1). Conclusions Incidence of both CD and UC are no longer rising significantly, but the location of CD at diagnosis continues to change with an increase in colonic location. Key messages What is already known? It is unclear whether the incidence of IBD has now plateaued in urbanised nations. Changes in Crohn’s disease location are often not reported in incidence studies and terminal ileal disease has usually been reported as the commonest site of disease What is new here? The incidence of UC and Crohn’s is no longer rising in Cardiff UK, but the phenotype has changed progressively over time with a continuing increase in colonic disease location and decrease in isolated terminal ileal disease How can this study help patient care? Understanding that Crohn’s colitis is the predominant location has implications for diagnostic tests and implications for treatment options IMPACT STATEMENT This work shows that although IBD incidence is no longer rising, the pattern of Crohn's disease is changing with more colonic disease and less isolated terminal ileal disease. PRACTITIONER RELEVANCE STATEMENT The changing pattern of Crohn's disease location has implications for diagnostic assessment and treatment of this disease.

Abstract A010: Molecular characteristics and prognosis of early-onset colorectal cancer according to detailed anatomical locations: Comparison to later-onset cases

Abstract Background: Evidence suggests that, compared to later-onset colorectal cancer (CRC), early-onset CRC (diagnosed before 50 years of age) occur more frequently in rectal location and less frequently in proximal colon location. Studies also indicate heterogeneity of molecular characteristics within early-onset CRCs and between early-onset and later-onset CRCs. Understanding how tumor molecular features and biological aggressiveness of early-onset CRC differ by detailed tumor location is important in personalized patient management. Methods: Using 14,004 CRC cases including 3,089 early-onset cases from The Cancer Genome Atlas and the Genetics and Epidemiology of CRC Consortium (GECCO), we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in cancers of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. We further conducted CRC-specific survival analyses of detailed tumor location stratified by molecular characteristics using multivariable Cox proportional hazards models. Results: The proportions of MSI-high, CIMP-high, and BRAF-mutated early-onset tumors gradually increased from the rectum (8.8%, 3.4%, and 3.5%, respectively) to the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF-mutated), followed by declines in the cecum for MSI-high (36%) and BRAF-mutated (4.6%) tumors. Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend &amp;lt;0.001) followed by an increase in the cecum (14%), while early-onset MSI-high cancer showed no such trend. In survival analyses, there was a trend for better CRC-specific survival from the cecum to sigmoid colon (Ptrend&amp;lt;0.001) (but not to rectum), which did not significantly differ by age of diagnosis (Pinteraction=0.61). Multivariable-adjusted hazard ratios (HRs) for sigmoid vs. cecum were 0.86 (95% CI, 0.64-1.14) for early-onset cases and 0.81 (95% CI, 0.70-0.93) for later-onset cases. Notably, the prognostic association of tumor location differed by MSI status (Pinteraction=0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better CRC-specific survival [Ptrend &amp;lt;0.001; multivariable-adjusted HR for the sigmoid colon (vs. cecum), 0.80; 95% CI, 0.70-0.92], whereas MSI-high tumors demonstrated an opposite cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI, 1.15-3.92). Conclusions: Our findings support biogeographical and pathogenic heterogeneity of CRC in different age groups and colorectal subsites. Both detailed colorectal location and tumor molecular features need to be accounted for prognostication of early-onset and later-onset CRCs to advance precision medicine. Citation Format: Tomotaka Ugai, Yin Cao, Koichiro Haruki, Tabitha A. Harrison, Daniel D. Buchanan, Peter T. Campbell, Andrew T. Chan, Steven Gallinger, Marc J. Gunter, Michael Hoffmeister, Mark A. Jenkins, Roger L. Milne, Polly A. Newcomb, Rish K. Pai, Andrew J. Pellatt, Robert E. Schoen, Bethany Van Guelpen, Michael O. Woods, Amanda I. Phipps, Ulrike Peters, Shuji Ogino. Molecular characteristics and prognosis of early-onset colorectal cancer according to detailed anatomical locations: Comparison to later-onset cases [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A010.

Sporadic Rectocolic Polyps Prevalence and Management

Abstract Objective To evaluate the prevalence of polyps and their treatments. Materials and Method This is a retrospective study conducted in our department over 20 years and 3 months between January 2000 and March 2021. All patients with colorectal polyps who underwent endoscopic resection were included. We evaluated the resection techniques and the management of complications. Results The total number of patients was 273, with a mean age of 57.26 ± 14.058 (18–90) and a M/W sex ratio of 2. The prevalence was 3.35% and the mean number of polyps was 1.33 ± 0.69. The most frequent symptoms were rectal bleeding (23.5%) and constipation (12.1%). The median size was 6 mm (4–12 mm). The left colonic location was the most frequent site (43%). All polyps were classified according to the Paris classification, with a predominance of sessile polyps in 45.75%, followed by pedunculated polyps, representing 42.4%. Endoscopic resection was performed either by biopsy forceps, polypectomy, or mucosectomy in 30.2%, 27.4%, and 25.4% of cases, respectively. Our study noted immediate bleeding in 1.5% of cases, and no perforations or late complications. All complications were treated endoscopically, and no patient required blood transfusion or surgical intervention. Conclusion Endoscopic resection of rectocolic polyps is the ideal treatment for these lesions. In our department, the prevalence was 3.35%, the most used resection techniques were forceps resection and polypectomy, and the complication rate was 1.5%.

Risk factors for perforation during colorectal endoscopic submucosal dissection

AbstractEndoscopic submucosal dissection (ESD) achieves higher en bloc resection rates than endoscopic mucosal resection in early colorectal neoplasms. However, perforation occurs more frequently during ESD. We aimed to identify the risk factors for perforation during colorectal ESD. A total of 161 patients treated with colorectal ESD at a tertiary center between January 2014 and December 2019 were enrolled in this retrospective study. Perforation was defined as a deep defect of the muscularis propria, with or without direct contact with connective tissue outside the colon. Clinical risk factors for perforation during ESD, including age, sex, tumor morphology, tumor size, tumor location, procedure time, en bloc resection rate, histology, and submucosal fibrosis, were analyzed. The mean size of the ESD specimens was 38.2 ± 24.6 mm. The overall en bloc resection rate was 98.1%. Perforations occurred during ESD in 31 out of 161 patients (19.3%). All perforations were successfully treated with endoscopic closure using the hemoclips and nonsurgical management. Emergency surgery was not required in our patients. On multivariate analysis, severe submucosal fibrosis (odds ratio [OR] 3.06; 95% confidence interval [CI] 1.23‐7.59; P = .016) and location in the right colon (OR 4.54; 95% CI 1.31‐15.79; P = .017) were independent risk factors. Perforation during colorectal ESD occurred in 31 patients (19.3%), but all patients had a good outcome without surgery. Submucosal fibrosis and its location are risk factors for perforation during ESD.

Regional Differences in Intestinal Contractile Responses to Radial Stretch in the Human Lower Gastrointestinal Tract.

Radial stretch evokes an increase or decrease in contractions in the lower gastrointestinal tract via mechanosensory enteric neurons that project into the muscle layers. We aim to elucidate the differences in stretch reflexes according to their location in the human colon. We used healthy intestinal smooth muscle tissue excised during elective colon cancer surgery. Conventional intracellular recordings from colonic muscle cells and tension recordings of colonic segments were performed. Radial stretch was evoked through balloon catheter inflation. Changes in the membrane potential and frequency, amplitude, and area under the curve of muscle contractions were recorded before and after the radial stretch at proximal and distal segment sites. In intracellular circular muscle recordings, hyperpolarization was noted at the distal site of sigmoid colonic segments after radial stretch, in contrast to depolarization at all other sites. In tension recordings at proximal ascending or sigmoid colonic segment sites, contractile activation was observed with statistically significant increases in the frequency, amplitude, and area under the curve after radial stretch. Distal sites of ascending and sigmoid colonic segments showed increase and decrease in contraction, respectively. Radial stretch in the human colon (in vitro) evokes excitatory activity at both proximal and distal sites of the ascending colon and at the proximal site of the sigmoid colon, whereas it elicits inhibitory activity at the distal site of the sigmoid colon.

Comparative Performance of Artificial Intelligence Optical Diagnosis Systems for Leaving in Situ Colorectal Polyps

Comparative Performance of Artificial Intelligence Optical Diagnosis Systems for Leaving in Situ Colorectal Polyps

Establishment of a model for predicting delayed post-polypectomy bleeding: A real-world retrospective study

Delayed post-polypectomy bleeding (DPPB) is the most common complication which occurs within 30 days after polypectomy, it has become rather common with the widespread of colorectal cancer screening. It is important to clarified predictors of DPPB and identify patients at high risk. This was a real-world retrospective study based on medical records from The First Affiliated Hospital of Nanjing Medical University. Cases of patients who underwent colonoscopic polypectomy between January 2016 and December 2020 were reviewed to identify risk factors of DPPB. We use the LASSO-Logistic regression analysis model to identify independent predictors and create a predictive model. The model finally got visualized by developing a nomogram. Colonoscopic polypectomy was done on 16,925 patients in our study. DPPB occurred in 125 (0.74%) of these instances. In multivariate analysis, age, sex, hypertension, polyp location, polyp size, and operative modality were found to be independent risk factors and were integrated for the construction of a nomogram. The model's C-index is 0.801 (95%CI: 0.761-0.846). We also found polyps located at the right semicolon and polyp ≥ 1 cm associated with active bleeding under the therapeutic colonoscopy. Young age, male, hypertension, polyp ≥ 1 cm, proximal colon location and operative modality were finally identified as significant predictors of DPPB. We developed and validated a nomogram which performs well in predicting the incidence of DPPB, the model we established can be used as a valuable screening tool to identify patients who are at high risk of bleeding.

Endoscopic polypectomy for malignant polyps: Should tumor location (right versus left side) guide clinical decisions?

BackgroundCurrent guidelines consider endoscopic resection appropriate treatment for malignant colon polyps with negative margins, low-grade histology, and no lymphovascular invasion. While increasing literature demonstrates a worse prognosis for advanced stage right- versus left-sided colon cancers after curative treatment, there is paucity of data regarding prognostic effect of location in patients undergoing endoscopic resection of T1 polyps. We hypothesized the more aggressive biologic behavior observed in advanced right-sided cancers would be similarly represented in malignant polyps, and this location would be associated with lower overall survival. MethodsThe National Cancer Database was queried for adults with T1NxMx tumors who underwent endoscopic polypectomy (2004–2017). Patients with positive margins or without follow-up information were excluded. ResultsA total of 2,337 patients met inclusion criteria; 22% had right-sided polyps. Endoscopically excised proximal tumors were more common in elderly, and those with public insurance and more comorbidities (all P < .01). Among patients with complete pathologic data, there were no statistical differences between right- and left-sided polyps with 1 cm median size, >92% without lymphovascular invasion, and 100% without tumor deposits. Univariate analysis showed 73% vs 86% 5-year overall survival for right versus left polyps (P < .01). After adjustment for available confounders, right-sided location remained significantly associated with worse overall survival (hazard ratio 1.49, 95% confidence interval 1.21–1.83). ConclusionIn this national cohort of patients with endoscopically excised malignant polyps, we identified right colon location as an independent prognostic factor associated with increased risk of mortality. Our data suggest polyp location should be taken into consideration when making clinical decisions regarding treatment and/or surveillance.

S2071 Natural Killer Polyp

Introduction: Natural killer (NK) cells are cytotoxic lymphocytes that can induce an innate immune response against tumors and virally-infected cells. NK cell enteropathy (NKCE) is clinically indolent although histologically it resembles NK/T-cell lymphomas.1 Therefore, accurate diagnosis is instrumental to avoid overtreatment.1 Case Description/Methods: A 45-year-old female presented with 2 episodes of nocturnal left lower quadrant “labor-like” pain lasting for 1-2 hours each, which were not alleviated by ibuprofen or acetaminophen. She described her subsequent bowel movements as bloody, skinny stool. Her pain was associated with abdominal tenderness for 3 days. She denied a change in weight or appetite but did endorse decreased energy over the last several months. Her family history is limited since she was adopted. Physical examination and lab tests were unremarkable. Colonoscopy showed a flat, 1-cm polyp with 3 erosions in the rectum. Excisional biopsy revealed polypoid fragments of rectal mucosa with atypical lymphoid infiltrate with NK cell phenotype involving predominantly the mucosa and multifocally through the muscularis mucosa (Figure 1A and 1B). Immunohistochemical staining was positive for CD3, CD7, CD56, and BCL2. Ki-67 highlighted approximately 90% of the lesional cells. These results were consistent with NKCE. The CT was unremarkable. It was decided to manage her conservatively. Repeat colonoscopy 6-months later revealed a post-polypectomy scar in the rectum (Figure 1C). Scar biopsy was negative for abnormal cells. She followed up with oncology and has been in remission for more than 5 years. Her most recent colonoscopy still showed an unchanged rectal scar. Discussion: The lack of systemic symptoms, the isolated colon location, and its EBV-negative staining point toward a diagnosis of NKCE rather than lymphoma. NKCE typically presents with vague abdominal symptoms and bleeding.1 Since NKCE mimics NK/T-cell lymphoma, it is important to accurately diagnose the disease to prevent erroneous overly aggressive treatment. Since this disease and the exact stimulus are not well established,1 further research needs to explore the appropriate standard of care for patients with NKCE.Figure 1.: A and B, histologic findings consistent with a diagnosis of natural killer cell enteropathy. C, post-polypectomy scar.

Kolorektální karcinom po transplantaci jater

Summary: Introduction: Patients after liver transplantation (LTx) have an increased risk of developing malignancies, especially skin malignancies and lymphomas. Colorectal cancer is one of the most common malignancies, its incidence may be higher after transplantation of certain organs. In liver transplant patients, the risk of developing CRC is not clearly known. Aim and methods: The aim of this work was to evaluate the incidence of CRC in patients after liver transplantation and to enrich these data with our own experience from our transplant center. Results: In the literature, the documented incidence of colorectal cancer ranges from comparable to twice as high, compared to the general population. Most studies evaluate incidence of different tumors after transplantatin of various organs irrespective of the indication for transplantation. An unequivocally proven risk factor is the presence of primary sclerosing cholangitis by ulcerative colitis, which is, however, a precancer in itself. Studies in which non-PSC and UC liver transplant recipients were evaluated separately mostly did not show an increased risk of CRC. Conclusion: According to most studies, the incidence of colorectal cancer in all liver transplant patients is slightly higher than in the general population. The risk of PSC/UC in liver transplant patients is significantly higher, which strongly supports the necessity of their regular endoscopic surveillance. In patients transplanted for other indications, the risk of developing CRC seems comparable with the general population. Posttransplant CRC is characterized by location in the right colon, diagnosis at a later stage and worse prognosis. Key words: transplantation – liver transplantion– colorectal carcinoma

Serological profiling of Crohn's disease and ulcerative colitis patients reveals anti-microbial antibody signatures.

BACKGROUNDThe healthcare burden of inflammatory bowel disease (IBD) is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis. AIMTo understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.METHODSWe performed serological profiling of 100 Crohn’s disease (CD) patients, 100 ulcerative colitis (UC) patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays. The study subjects were randomly divided into discovery (n = 150) and validation (n = 150) sets. Statistical analysis was performed using R packages. RESULTSAnti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses. We identified novel antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) showing higher prevalence in CD patients relative to healthy controls. We also identified antibodies against the antigen of Streptococcus pyogenes (SPy_2009) showing higher prevalence in healthy controls relative to UC patients. Using these novel antibodies, we built biomarker panels with area under the curve (AUC) of 0.81, 0.87, and 0.82 distinguishing CD vs control, UC vs control, and CD vs UC, respectively. Subgroup analysis revealed that penetrating CD behavior, colonic CD location, CD patients with a history of surgery, and extensive UC exhibited highest antibody prevalence among all patients. We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.CONCLUSIONWe have identified antibody signatures for CD and UC using a comprehensive analysis of anti-microbial antibody response in IBD. These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and, after future validation, should aid early and accurate diagnosis of IBD.

Preliminary results of laparoscopic complete mesocolic excision for colon cancer treatment

Background: Laparoscopic complete mesocolic excision (CME) has more lymph nodes resected than traditional laparoscopic colectomy. The laparoscopic CME has not been extensively described as a safe strategy. Objective: Evaluate clinical characteristics and preliminary results of laparoscopic CME in colon cancer. Methods: A prospective study included 22 patients at the Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital from May 2021 to May 2022. Results: Mean age was 63.6 ± 14.1, and males accounted for 54.5%. ASA 1 accounted for the majority, with a rate of 77.3%. 45.5% of patients with middle and high nutritional risk. The sigmoid colon accounts for the most with 40.9%. The prevalence of splenic flexure colon, the same transverse colon location was a minor proportion at 4.5%. The sigmoidectomy and sigmoidectomy + a part of upper third rectal resection accounted for 40.9%. The mean (range) of the length of hospital stay was 7.3 ± 1.5 days. The specimen length, mesentery width, and lymph nodes average were 31.2 ± 8.2 cm, 9.3 ± 1.7 cm, and 62.2 ± 18.6, respectively. The average tumor size was 4.9 ± 1.6 cm. The analytical plane achieved 86.4% of the complete mesenteric plane. AJCC 8th Stage I after surgery accounted for 40.9%, followed by stages IIIb, and IIa with 31.8% and 18.2%, respectively. Only three patients had complications of surgical site infection, accounting for 13.6%, and one patient with abdominal subcutaneous emphysema + urinary retention accounted for 4.5%. Conclusion: preliminary results of laparoscopic CME colectomy are feasible, safe, and reliable with maximal lymph node retrieval Key words: CME, laparoscopic, colon cancer, treatment, initial, preliminary

Transcriptomic Response to Calcium in Normal Colon Organoids is Impacted by Colon Location and Sex.

A chemopreventive role for calcium in colorectal cancer is still unclear. Here, we identify mechanisms through which calcium supplementation may reduce risk. Calcium supplementation increased differentiation and altered expression of colorectal cancer-related genes in a large study of patient-derived colon organoids. These findings were influenced by colon location and sex.

Adoption of Optimal Small (6-9mm) Colorectal Polyp Resection Technique Over Time.

Cold snare polypectomy (CSP) is the preferred resection technique for small (6-9mm) polyps due to lower rate of incomplete resection compared to cold forceps polypectomy (CFP) and improved safety profile over hot snare polypectomy (HSP). To describe resection techniques for small (6-9mm) polyps and determine factors associated with sub-optimal technique. This was retrospective cohort study of colonoscopies performed by gastroenterological and surgical endoscopists from 2012 to 2019 where at least one 6-9mm polyp was removed. Patient, provider, and procedure characteristics were collected. Univariate and multivariate regression analyses were performed to determine factors associated with sub-optimal technique. In total, 773 colonoscopies where 1,360 6-9mm polyps removed by 21 endoscopists were included. CSP was used for 1,122 (82.5%), CFP for 61 (4.5%), and HSP for 177 (13.0%). Surgeon specialty was associated with CFP use (aOR 7.81; 95% CI 3.02-20.16). Polyp location in left colon (aOR 1.65; 95% CI 1.17-2.33) and pedunculated morphology (aOR 12.76; 95% CI 7.24-22.50) were associated with HSP. There was a significant increase in overall CSP use from 30.4% in 2012 to 96.8% in 2019. 82.5% of all 6-9mm polyps removed from 2012 to 2019 were removed using a cold snare with significant increase in CSP from 2012 to 2019. Differences in how optimal technique was adopted over time based on specialty highlight the need for standardized practice guidelines and quality monitoring.