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Objectives: To evaluate the performance of stool methylated syndecan2 (mSDC2), methylated septin9 (mSEPT9), fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in detecting colorectal neoplasia and adenomas. Methods: Blood-borne CEA, CA125, and CA199 levels were measured by electrochemiluminescence. The SDC2 methylation was detected by Methylation Detection Kit for Human SDC2 Gene (Real time PCR), and the SEPT9 methylation was detected by the Septin9 Gene Methylation Detection Kit based on PCR fluorescent probe assay. The colonoscopy combined with tissue biopsy pathology was used as a validation criterion for colorectal neoplasia. Results: In detecting colorectal neoplasia, the AUCs of mSDC2, FOBT and mSEPT9 were 0.935 (95% CI: 0.915-0.956, P<0.001), 0.824 (95% CI: 0.617-1.000, P<0.001) and 0.671 (95% CI: 0.511-0.831, P<0.001), respectively. The sensitivity of mSDC2, FOBT and mSEPT9 were 100.0%, 66.7% and 40.0%, respectively. But the AUC of CEA, CA125 and CA199 were not statistically significant for colorectal neoplasia (all P>0.05). The combined application of mSEPT9 and mSDC2 showed the best predictive performance (AUC: 0.956, 95% CI: 0.887~1.000). For adenomas, the AUC of FOBT was extremely low (AUC: 0.524, 95% CI: 0.502-0.545, P=0.004). The CEA, CA125, CA199, mSEPT9 and mSDC2 were not statistically significant in detecting adenomas (all P>0.05). Conclusions: For individual tests, FOBT and mSDC2 are relatively better indicators for detecting colorectal neoplasia compared to mSEPT9, CEA, CA125 and CA199. The combined form of mSEPT9 and mSDC2 to detect colorectal neoplasia has good predictive performance. However, none of these indicators demonstrated significant predictive power for detecting adenomas in our study. [ABSTRACT FROM AUTHOR]

Background: Colorectal neoplasia and diverticulosis are common findings on colonoscopies. While adenomas are precursors to colorectal cancer, diverticulosis is usually asymptomatic but can lead to diverticulitis. Despite their prevalence and coexistence, the relationship between these conditions remains unclear. This study investigates whether diverticulosis is associated with adenomas, considering shared risk factors and potential inflammation-driven mechanisms. Methods: We examined 6154 asymptomatic individuals undergoing colorectal cancer screening in Austria. Diverticulosis and colorectal neoplasia were documented during screenings based on macroscopic definitions. Advanced neoplasia was defined as polyps >1 cm or high-grade dysplasia. Associations between diverticulosis and neoplastic findings were assessed using univariate and multivariable logistic regression models. Results: Although the overall incidence of any polypoid lesion was higher in the diverticulosis group (37% vs. 30%), statistical analysis revealed a comparable rate of advanced neoplasms in both groups. Importantly, no significant link between diverticulosis and advanced neoplasms was found (OR 1.125; 95% CI: 0.933 to 1.357, p = 0.218) even after adjusting for confounding factors. In a univariate analysis, a statistically significant association between diverticulosis and the presence of any colorectal polyps was identified (OR 1.388; 95% CI: 1.244–1.549, p < 0.0001). However, after adjusting for confounding factors in model 2 (OR 1.065, 95% CI: 0.942 to 1.204, p = 0.314) and model 3 (OR 1.071, 95% CI: 0.925 to 1.239, p = 0.360), this effect was also not statistically significant. Conclusions: Patients with diverticulosis share demographic and clinical features with those at risk of colorectal neoplasia, such as older age, male gender, and higher cardiometabolic risk. However, diverticulosis does not independently increase the risk of advanced colorectal neoplasia or unspecified polypoid lesions. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Trial Registration The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.To explore the trade‐off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.We included first participation in biennial FIT screening for 47,265 individuals aged 50–74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen‐detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g.At the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post‐colonoscopy bleeding rates were 0.8% and 1.7%, respectively.Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country‐specific information on adverse events.Clinicaltrials.gov identifier: NCT01538550 [ABSTRACT FROM AUTHOR]

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

Abstract Colorectal cancer is a major cause of cancer-related deaths within the Australian population. Colonoscopy and polypectomy represent effective forms of prevention. Factors such as diabetes, hypertension and dyslipidaemia have been linked to adenoma development across a range of ethnicities, however there are limited data from the Australian population. This study investigates established and potential risk factors for early colorectal neoplasia in an Australian population. This was a prospective, observational case-control study in subjects aged 20–85 years, referred for outpatient colonoscopy. Clinical, anthropometric, and biochemical variables were collected at baseline. Polyps were classified as conventional adenomas or sessile serrated lesions, and correlated with clinical and biochemical variables. The study included 357 subjects, median age 55 years (IQR: 43.0–64.0), and 52.9% were female. 41.7% had metabolic syndrome. Multiple positive associations were observed in those over 40 years and with a BMI ≥ 25, including any polyp (aOR: 2.26; 95%CI: 1.22–4.18); adenoma (aOR: 2.64; 95%CI: 1.31–5.31); and, non-advanced adenoma (aOR: 2.66; 95%CI: 1.25–5.68). Our study demonstrates that elevated BMI is an independent risk factor for colorectal neoplasia in Australians undergoing colonoscopy. Further efforts should be focused on both diet and weight optimization in the general population given these findings and the recent national statistics indicating that almost two-thirds of the population are either overweight or obese.

Background: Frailty has been associated with increased postoperative mortality and morbidity; however, the use of the modified frailty index (mFI-11) to assess patients undergoing surgery for diverticular disease has not been widely assessed. This paper aims to examine frailty, evaluated by mFI-11, to assess postoperative morbidity and mortality among patients undergoing operative intervention for colonic diverticular disease. Methods: We used data from the Healthcare Cost and Utilization Project National Inpatient Sample (October 1, 2015–December 31, 2019). ICD-10-CM codes were utilized to identify a cohort of adult patients with a primary admission diagnosis of diverticulitis. mFI-11 items were adapted to correspond with ICD-10-CM codes. Patients were stratified into robust (mFI < 0.27) and frail (mFI ≥ 0.27) groups. Primary outcomes were in-hospital postoperative morbidity and mortality. Secondary outcomes included system-specific postoperative complications, length of stay (LOS), total admission cost, and discharge disposition. Multivariable regression models were fit. Results: Of the 26,826 patients, there were 24,194 patients with mFI-11 < 0.27 (i.e., robust) and 2,632 patients with mFI-11 ≥ 0.27 (i.e., frail). Adjusted analysis showed significant increases in postoperative mortality (aOR 2.16, 95% CI 1.38–3.38, p = 0.001) and overall postoperative morbidity (aOR 1.84, 95% CI 1.65–2.06, p < 0.001). LOS was higher in the frail group (MD 1.78 days, 95% CI 1.46–2.11, p < 0.001) as well as total cost (MD $25,495.19, 95% CI $19,851.63-$31,138.75, p < 0.001). Conclusion: In the elective setting, a high mFI-11 (i.e., presence of the variables comprising the index) could alert clinicians to the possibility of implementing preoperative optimization strategies. In the emergent setting, a high mFI-11 may help guide prognostication for these vulnerable patients. [ABSTRACT FROM AUTHOR]

Background: The global burden of obesity has reached epidemic proportions, placing great strain on the North American healthcare system. We designed a retrospective cohort database study comparing postoperative morbidity and healthcare resource utilization between patients living with and without obesity undergoing surgery for colorectal cancer. Methods: Adult patients undergoing resection for colorectal cancer were identified from the 2015 to 2019 National Inpatient Sample database. Patients were stratified according to obesity status (i.e., body mass index of 30 kg/m2). Propensity score matching (PSM) with 1:1 nearest‐neighbour matching was performed according to demographic, operative, and hospital characteristics. The primary outcome was postoperative morbidity. Secondary outcomes included system‐specific postoperative complications, postoperative mortality, length of stay, total admission healthcare cost, and post‐discharge disposition. McNemar's and Wilcoxon matched pairs signed rank tests were performed. Results: After PSM, 7565 non‐obese and 7565 obese patients were included. Patients with obesity had a 10% increase in relative risk of overall in‐hospital postoperative morbidity (23.1% versus 25.6%, P = 0.0015) and a $4564 increase in hospitalization cost ($70 248 USD versus $74 812 USD, P = 0.0004). Patients with obesity were more likely to require post‐operative ICU admission (5.0% versus 8.0%, P < 0.0001) and less likely to be discharged home after their index operation (68.3% versus 64.2%, P = 0.0022). Conclusion: Patients with obesity undergoing surgery for colorectal cancer may be at an increased risk of in‐hospital postoperative morbidity. They may also be more likely to have increased hospitalization costs, post‐operative ICU admissions, and to not be discharged directly home. Preoperative optimization via weight loss strategies should be further explored. [ABSTRACT FROM AUTHOR]

ObjectivesTo evaluate the performance of stool methylated syndecan2 (mSDC2), methylated septin9 (mSEPT9), fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in detecting colorectal neoplasia and adenomas.MethodsBlood-borne CEA, CA125, and CA199 levels were measured by electrochemiluminescence. The SDC2 methylation was detected by Methylation Detection Kit for Human SDC2 Gene (Real time PCR), and the SEPT9 methylation was detected by the Septin9 Gene Methylation Detection Kit based on PCR fluorescent probe assay. The colonoscopy combined with tissue biopsy pathology was used as a validation criterion for colorectal neoplasia.ResultsIn detecting colorectal neoplasia, the AUCs of mSDC2, FOBT and mSEPT9 were 0.935 (95% CI: 0.915-0.956, P0.05). The combined application of mSEPT9 and mSDC2 showed the best predictive performance (AUC: 0.956, 95% CI: 0.887~1.000). For adenomas, the AUC of FOBT was extremely low (AUC: 0.524, 95% CI: 0.502-0.545, P=0.004). The CEA, CA125, CA199, mSEPT9 and mSDC2 were not statistically significant in detecting adenomas (all P>0.05).ConclusionsFor individual tests, FOBT and mSDC2 are relatively better indicators for detecting colorectal neoplasia compared to mSEPT9, CEA, CA125 and CA199. The combined form of mSEPT9 and mSDC2 to detect colorectal neoplasia has good predictive performance. However, none of these indicators demonstrated significant predictive power for detecting adenomas in our study.

Background and Aims: Cardiovascular disease and colorectal cancer (CRC) are significant health problems and share some risk factors. The aim of our study was to develop and validate a predictive score for advanced colorectal neoplasia (CRN) based on risk factors for cardiovascular disease and CRC. Materials and Methods: A cross-sectional study comprising a derivation cohort and an external validation cohort of 1049 and 308 patients, respectively. A prediction score for advanced CRN (CRNAS: Colorectal Neoplasia Advanced Score) was developed from a logistic regression model, comprising sex, age, first-degree family history for CRC, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, body mass index, diabetes, smoking, and antihypertensive treatment. Other cardiovascular risk scores (Framingham–Wilson, REGICOR, SCORE, and FRESCO) were also used to predict the risk of advanced CRN. The discriminatory capacity of each score was evaluated using the area under the curve (AUC). Results: CRN were found in 379 subjects from the derivation cohort (36%), including 228 patients (22%) with an advanced CRN. Male sex, age, diabetes, and smoking were identified as independent risk factors for advanced CRN. The newly created score (CRNAS) showed an AUC of 0.68 (95% CI: 0.64–0.73) for advanced CRN, which was better than cardiovascular risk scores (p < 0.001). In the validation cohort, the AUC of CRNAS for advanced CRN was 0.67 (95% CI: 0.57–0.76). Conclusions: The newly validated CRNAS has a better discriminatory capacity to predict advanced CRN than cardiovascular scores. It may be useful for selecting candidates for screening colonoscopy, especially in those with cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Introduction Colorectal cancer is the third most common malignant neoplasm worldwide, with ∼ 150 thousand new cases each year. Screening policies have brought significant progress due to the possibility of early diagnosis and polyp resection. Therefore, there is a need for continuous evaluation of the quality of colonoscopies based on well-established criteria in the literature.

Abstract Objectives Endoscopic submucosal dissection (ESD) enables minimally invasive resection of superficial gastrointestinal neoplasms en bloc regardless of size. The Japan narrow band imaging expert team (JNET) classification utilizes optical magnification and narrow band imaging (NBI) to predict pathology. In North America, ESD is far from ubiquitous, and regional outcomes are not widely described. To date there are no North American studies describing the application and yield of the JNET classification as applied in the practice of ESD. Methods A retrospective, single‐center, cohort analysis was performed on a prospectively maintained database of ESD procedures. Between July 2016 and February 2023, all consecutive patients treated with ESD for colorectal lesions were identified and stratified by lesion location, JNET, NBI International Colorectal Endoscopic, lateral spreading tumors, and Paris classifications. Univariate analysis was used for clinicopathological data. p

Abstract Background Surveillance colonoscopy decreases colorectal cancer mortality; however, lesions are occasionally missed. Although an appropriate surveillance interval is indicated, variations may occur in the methods used, such as scope manipulation or observation. Therefore, individual endoscopists may miss certain areas. This study aimed to verify the effectiveness of performing repeat colonoscopies with a different endoscopist from the initial procedure. Methods We retrospectively reviewed a database of 8093 consecutive colonoscopies performed in the Omori Red Cross Hospital from January 1st 2018 to June 30th 2021. Data from repeat total colonoscopies performed within three months were collected to assess missed lesions. The patients were divided into two groups according to whether the two examinations were performed by different endoscopists (group D) or the same endoscopist (group S). The primary outcome in both groups was the missed lesion detection rate (MLDR). Results Overall, 205 eligible patients were analyzed. In total, 102 and 103 patients were enrolled in groups D and S, respectively. The MLDR was significantly higher in group D (61.8% vs. 31.1%, P 6 min) (odds ratio, 3.10; 95% CI, 1.12–8.61) as significant variables. Conclusions Overall, our study showed a significant improvement in the detection of missed lesions when performed by different endoscopists. When performing repeat colonoscopy, it is desirable that a different endoscopist perform the second colonoscopy. Trial registration This study was approved by the Institutional Review Board of the Omori Red Cross Hospital on November 28, 2022 (approval number:22–43).

Prebiotic and probiotic supplementation and yogurt consumption (a probiotic food) alter gut microbial diversity, which may influence colorectal carcinogenesis. This systematic review evaluates the existing literature on the effect of these nutritional supplements and yogurt consumption on colorectal neoplasia incidence among adults. We systematically identified ten randomized controlled trials and observational studies in adults age ≥ 18 without baseline gastrointestinal disease. Prebiotics included inulin, fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, and β-glucans. Probiotics included bacterial strains of Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Bacillus, Pediococcus, Leuconostoc, and Escherichia coli. Synbiotic supplements, a mixture of both prebiotic and probiotic supplements, and yogurt, a commonly consumed dietary source of live microbes, were also included. We defined colorectal neoplasia as colorectal adenomas, sessile serrated polyps, and colorectal cancer (CRC). Overall, findings suggest a moderate decrease in risk of adenoma and CRC for high levels of yogurt consumption compared to low or no consumption. Prebiotic supplementation was not associated with colorectal neoplasia risk. There was some evidence that probiotic supplementation may be associated with lower risk of adenomas but not with CRC incidence. Higher yogurt consumption may be associated with lower incidence of colorectal neoplasia. We found little evidence to suggest that prebiotic or probiotic supplements are associated with significant decreases in CRC occurrence.

Background & Aims: Human sporadic colorectal cancer (CRC) results from a multistep pathway with sequential acquisition of specific genetic mutations in the colorectal epithelium. Modeling CRC in vivo is critical for understanding the tumor microenvironment. To accurately recapitulate human CRC pathogenesis, mouse models must include these multi-step genetic abnormalities. The aim of this study was to generate a sporadic CRC model that more closely mimics this multi-step process and to use this model to study the role of a novel Let7 target PLAGL2 in CRC pathogenesis. Methods: We generated a CRISPR/Cas9 somatic mutagenesis mouse model that is inducible and multiplexed for simultaneous inactivation of multiple genes involved in CRC pathogenesis. We used both a doxycycline-inducible transcriptional activator and a doxycycline-inactivated transcriptional repressor to achieve tight, non-leaky expression of the Cas9 nickase. This mouse has transgenic expression of multiple guide RNAs to induce sporadic inactivation in the gut epithelium of 4 tumor suppressor genes commonly mutated in CRC, Apc, Pten, Smad4, and Trp53. These were crossed to Vil-LCL-PLAGL2 mice, which have Cre-inducible overexpression of PLAGL2 in the gut epithelium. Results: These mice exhibited random somatic mutations in all 4 targeted tumor suppressor genes, resulting in multiple adenomas and adenocarcinomas in the small bowel and colon. Crosses with Vil-LCL-PLAGL2 mice demonstrated that gut-specific PLAGL2 overexpression increased colon tumor growth. Conclusions: This conditional model represents a new CRISPR/Cas9-mediated mouse model of colorectal carcinogenesis. These mice can be used to investigate the role of novel, previously uncharacterized genes in CRC, in the context of multiple commonly mutated tumor suppressor genes and thus more closely mimic human CRC pathogenesis.

Background: Surveillance colonoscopy decreases colorectal cancer mortality; however, lesions are occasionally missed. Although an appropriate surveillance interval is indicated, variations may occur in the methods used, such as scope manipulation or observation. Therefore, individual endoscopists may miss certain areas. This study aimed to verify the effectiveness of performing repeat colonoscopies with a different endoscopist from the initial procedure. Methods: We retrospectively reviewed a database of 8093 consecutive colonoscopies performed in the Omori Red Cross Hospital from January 1st 2018 to June 30th 2021. Data from repeat total colonoscopies performed within three months were collected to assess missed lesions. The patients were divided into two groups according to whether the two examinations were performed by different endoscopists (group D) or the same endoscopist (group S). The primary outcome in both groups was the missed lesion detection rate (MLDR). Results: Overall, 205 eligible patients were analyzed. In total, 102 and 103 patients were enrolled in groups D and S, respectively. The MLDR was significantly higher in group D (61.8% vs. 31.1%, P < 0.0001). Multivariate logistic regression analysis for the detection of missed lesions identified performance by the different endoscopists (odds ratio, 3.38; 95% CI, 1.81–6.30), and sufficient withdrawal time (> 6 min) (odds ratio, 3.10; 95% CI, 1.12–8.61) as significant variables. Conclusions: Overall, our study showed a significant improvement in the detection of missed lesions when performed by different endoscopists. When performing repeat colonoscopy, it is desirable that a different endoscopist perform the second colonoscopy. Trial registration: This study was approved by the Institutional Review Board of the Omori Red Cross Hospital on November 28, 2022 (approval number:22–43). [ABSTRACT FROM AUTHOR]

Introduction Colonic self-expanding metal stent (SEMS) placement is the preferred method for palliation of malignant colonic obstruction. We analyzed outcomes of patients who underwent colonic SEMS placement for palliation at a tertiary care oncology center in Western India. Methods Retrospective review of the endoscopy database was done for patients who underwent colonic SEMS placement at our center between January 2013 and September 2021. Demographic details, intent of stent placement, site of obstruction, length of stricture, technical success of stenting, clinical success, and complications (both immediate and long term) were noted. Results Sixty-one patients underwent colonic SEMS placement during the study period (mean age 53.6 years, 50.7% men). Obstruction was due to primary colonic malignancy in 43 (70.5%) patients and extracolonic malignancies in 18 (29.5%) patients. Most common extracolonic malignancy was gallbladder cancer in 8 (44.4%) patients. Most common site of obstruction was sigmoid colon in 18 (29.5%) patients. Proximal colonic obstruction was seen in 17 (27.9%) patients. Peritoneal metastases were seen in 26 (42.6%) patients. Colonoscopy revealed an impassable stenosis in 58 (95.1%) patients. Median length of stricture was 5 cm (range 2–9 cm). Technical success was achieved in 98.3% (60/61). Clinical success was achieved in 51 (86.4%) patients. Perforation during colonic SEMS placement was seen in 2 (3.4%) patients. Stent migration was seen in 3 (5.9%) patients, needing surgery for retrieval in all 3 patients. Over a median follow-up of 9 months (0–21 months), stent block was seen in 7 (13.7%) patients. Stent block developed after a median period of 6 months. Of these patients, three patients underwent SEMS placement within the SEMS and the other four patients underwent surgery. Conclusion Colonic SEMS placement achieves good palliation of malignant colonic obstruction in approximately 87% patients. Long-term complications like obstruction occur in a few patients after a median duration of 6 months.

Abstract Background In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 µg Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT. Methods This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals’ perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening. Discussion The aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality. Trial registration: ClinicalTrials.gov, NCT05423886, June 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05423886

Objectives: Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. Methods: Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. Results: Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). Conclusion: Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development. [ABSTRACT FROM AUTHOR]

Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease which is associated with Inflammatory Bowel Disease (IBD) in 70% of cases. It seems PSC/IBD is a distinct phenotype that is different from PSC, and IBD alone. Hence, we review the epidemiology, pathogenesis, natural course and management of PSC/IBD before and after LT for PSC. Extensive colitis, rectal sparing, backwash ileitis, and mild symptoms are the characteristics of IBD coexisting with PSC. Moreover, PSC patients with concurrent IBD have higher risk of cholangiocarcinoma, and colorectal neoplasia predominantly in right colon and at younger age. Therefore, it is essential to monitor these individuals continuously. It is interesting to note that the course of IBD (ulcerative colitis) after liver transplantation (LT) for PSC varies greatly, and some patients may develop worsening colitis after LT despite immunosuppressive regimens. As well, management of these patients was discussed in this review. [ABSTRACT FROM AUTHOR]

Data on the frequency of colorectal neoplasia in sporadic ampullary tumors remains scarce. We retrospectively reviewed 135 patients undergoing endoscopic ampullectomy from January 2018 to July 2021, and identified 95 patients with sporadic ampullary adenoma who underwent total colonoscopy. Colonoscopy findings were compared with 380 asymptomatic controls using the chi-squared test. Whole-exome sequencing (WES) was performed on one patient with synchronous adenomas of the ampulla of Vater and ascending colon. Colorectal polyps were present in 60% of Cases vs. 34.7% of Controls (P = 0.001), advanced adenoma in 20% vs. 5.5%, and adenocarcinoma in 4.2% vs. 0.8%. Cases tended to have larger polyps than Controls (P <0.001), while there was no difference in polyp location and histology between the two groups. The odds ratio of all the colorectal lesions, advanced colorectal adenoma and adenocarcinoma in C ases was 1.7, 4.2, and 4, respectively. WES in one patient revealed that both of ampullary adenoma and colonic adenoma shared somatic ABCB1 mutation. The frequency of colorectal polyps or neoplasia was significantly higher in Cases than Controls. We proposed that ampullary neoplasia is analogous to colon lesions and warrants total colonoscopy screening in patients diagnosed with ampullary tumors. [ABSTRACT FROM AUTHOR]

Introduction: Pathogenic strains of Escherichia coli have been clearly identified as the causative agents of extraintestinal and diarrheal infections; however, the etiopathogenic role of E. coli in other conditions, including colorectal cancer, remains unclear. Methods: This study aimed to characterize mucosal E. coli isolates (n = 246) from 61 neoplasia patients and 20 healthy controls for the presence of 35 genetic determinants encoding known virulence factors. Results: Virulence determinants encoding invasin (ibeA), siderophore receptor (iroN), S-fimbriae (sfa), and genotoxin (usp) were more prevalent among E. coli isolated from patients with neoplasia compared to the control group (p < 0.05). In addition, the prevalence of these virulence determinants was increased in more advanced neoplasia stages (padj < 0.0125). Compared to patients with advanced colorectal adenoma and carcinoma, the ibeA gene was rarely found in the control group and among patients with non-advanced adenoma (p < 0.05), indicating its potential as the advanced-neoplasia biomarker. Patients with neoplasia frequently had E. coli strains with at least one of the abovementioned virulence factors, whereby specific combinations of these virulence factors were found. Discussion: These findings suggest that E. coli strains isolated from patients with colorectal neoplasia possess several virulence factors, which could contribute to the development of neoplastic processes in the large intestine. [ABSTRACT FROM AUTHOR]

Introduction: Educational status is used as a proxy for socioeconomic status. While lower levels of education are generally associated with poorer health, the data on the relationship between educational status and colorectal neoplasia is heterogenous. The aim of our study was to examine this relationship and to adjust the association between educational status and colorectal neoplasia for other health parameters. Methods: We included 5977 participants undergoing a screening colonoscopy in Austria. We split the cohort into patients with lower (n = 2156), medium (n = 2933), and higher (n = 459) educational status. Multivariable multilevel logistic regression models were fitted to evaluate the association between educational status and the occurrence of any or advanced colorectal neoplasia. We adjusted for age, sex, metabolic syndrome, family history, physical activity, alcohol consumption, and smoking status. Results: We found that the rates of any neoplasia (32%) were similar between the educational strata. However, patients with higher (10%) educational status evidenced significantly higher rates of advanced colorectal neoplasia compared to medium (8%) and lower (7%) education. This association remained statistically significant after multivariable adjustment. The difference was entirely driven by neoplasia in the proximal colon. Conclusion: Our study found that higher educational status was associated with a higher prevalence of advanced colorectal neoplasia compared to medium and lower educational status. This finding remained significant even after adjusting for other health parameters. Further research is needed to understand the underlying reasons for the observed difference, especially with regard to the specific anatomical distribution of the observed difference. [ABSTRACT FROM AUTHOR]

Background: A Hartmann operation, which is the intervention by which the lower part of the sigmoid and the upper part of the rectum are resected with the closing of the rectal stump and end colostomy, has as its indications: advanced or complicated rectosigmoid neoplasm, moderate biological condition of the patient, peritoneal sepsis, intestinal occlusion and fragile colonic wall, especially in the context of inflammatory changes. The Hartmann procedure can save lives even at the cost of a stoma reversal failure. Methods: The cases operated with the Hartmann procedure by an open approach or laparoscopic approach in our clinic, between 1 January 2016 and 31 December 2020, were admitted in this study and their medical records were reviewed, also making a comparison between the two types of approach. Univariate statistical comparisons but also a multivariate analysis was performed. Results: We performed 985 operations for intestinal and colonic occlusion (7.15% of the total operations in the clinic), 531 (54%) were non-tumor occlusions and 454 (46%) were occlusive tumors (88 Hartmann operations). Of these, 7.3% were laparoscopically performed (7 laparoscopic Hartmann operations and 23 diagnostic laparoscopies). A total of 11 cases (18%) also had colonic perforation. We compared laparoscopic Hartmann with open Hartmann and observed the benefits of laparoscopy for postoperative morbidity and mortality. The presence of pulmonary and cardiac morbidities is associated with the occurrence of general postoperative morbidities, while peritonitis is statistically significantly associated with the occurrence of local complications that are absent after the laparoscopic approach. Conclusions: The Hartmann procedure is still nowadays an operation widely used in emergency situations. Laparoscopy may become standard for the Hartmann procedure and reversal of the Hartmann procedure, but the percentage of laparoscopy remains low due to advanced or complicated colorectal cancer, poor general condition both at the first and second intervention, and the difficulties of reversal of the Hartmann procedure. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation. Summary Background Data: Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions. Methods: Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, nonadenoma and adenoma-adjacent mucosa were collected along with clinical and dietary information. 16S rRNA gene libraries were generated using V4 primers. DADA2 processed sequence reads and custom R-scripts quantified microbial diversity. Linear regression identified differential taxonomy and diversity in microbial communities and machine learning identified adenoma former microbial signatures. Results: One hundred four subjects were included, 46% with adenomas. Mucosal and fecal samples were dominated by Firmicutes and Bacteroidetes whereas Firmicutes and Proteobacteria were most abundant in oral communities. Mucosal communities harbored significant microbial diversity that was not observed in fecal or oral communities. Random forest classifiers predicted adenoma formation using fecal, oral, and mucosal amplicon sequence variant (ASV) abundances. The mucosal classifier reliably diagnosed adenoma formation with an area under the curve (AUC) = 0.993 and an out-of-bag (OOB) error of 3.2%. Mucosal classifier accuracy was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. In contrast, classifiers built using fecal and oral samples manifested high OOB error rates (47.3% and 51.1%, respectively) and poor diagnostic abilities (fecal and oral AUC = 0.53). Conclusion: Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation. [ABSTRACT FROM AUTHOR]

Abstract Background Medical evidence from more recent observational studies may significantly alter our understanding of disease incidence and progression, and would require recalibration of existing computational and predictive disease models. However, it is often challenging to perform recalibration when there are a large number of model parameters to be estimated. Moreover, comparing the fitting performances of candidate parameter designs can be difficult due to significant variation in simulated outcomes under limited computational budget and long runtime, even for one simulation replication. Methods We developed a two-phase recalibration procedure. As a proof-of-the-concept study, we verified the procedure in the context of sex-specific colorectal neoplasia development. We considered two individual-based state-transition stochastic simulation models, estimating model parameters that govern colorectal adenoma occurrence and its growth through three preclinical states: non-advanced precancerous polyp, advanced precancerous polyp, and cancerous polyp. For the calibration, we used a weighted-sum-squared error between three prevalence values reported in the literature and the corresponding simulation outcomes. In phase 1 of the calibration procedure, we first extracted the baseline parameter design from relevant studies on the same model. We then performed sampling-based searches within a proper range around the baseline design to identify the initial set of good candidate designs. In phase 2, we performed local search (e.g., the Nelder-Mead algorithm), starting from the candidate designs identified at the end of phase 1. Further, we investigated the efficiency of exploring dimensions of the parameter space sequentially based on our prior knowledge of the system dynamics. Results The efficiency of our two-phase re-calibration procedure was first investigated with CMOST, a relatively inexpensive computational model. It was then further verified with the V/NCS model, which is much more expensive. Overall, our two-phase procedure showed a better goodness-of-fit than the straightforward employment of the Nelder-Mead algorithm, when only a limited number of simulation replications were allowed. In addition, in phase 2, performing local search along parameter space dimensions sequentially was more efficient than performing the search over all dimensions concurrently. Conclusion The proposed two-phase re-calibration procedure is efficient at estimating parameters of computationally expensive stochastic dynamic disease models.

Abstract Background Colorectal cancer is one of the most common cancers in the world. Several studies suggest using the Asia-Pacific colorectal screening (APCS) score and its modified versions to select high-risk populations for early colonoscopy, but external validation remains rare, and which score should be selected for CRC screening in China is unclear. Validation of multiple scores in the same population might help to choose the best performing score. Methods We conducted a cross-sectional study under the framework of Cancer Screening Program in Urban China, data from asymptomatic colorectal cancer screening in Xuzhou was used to validate the APCS score, the colorectal neoplasia predict (CNP) score, the Korean colorectal screening (KCS) score, the Modified APCS score and the 8-point risk score in predicting colorectal advanced neoplasia (CAN). Results 1804 subjects were included in the analysis and 112 CAN (6.21%) was detected. In each score, the detection rate of CAN was higher in the high-risk group than in the non-high-risk group (P

IntroductionPathogenic strains of Escherichia coli have been clearly identified as the causative agents of extraintestinal and diarrheal infections; however, the etiopathogenic role of E. coli in other conditions, including colorectal cancer, remains unclear.MethodsThis study aimed to characterize mucosal E. coli isolates (n = 246) from 61 neoplasia patients and 20 healthy controls for the presence of 35 genetic determinants encoding known virulence factors.ResultsVirulence determinants encoding invasin (ibeA), siderophore receptor (iroN), S-fimbriae (sfa), and genotoxin (usp) were more prevalent among E. coli isolated from patients with neoplasia compared to the control group (p < 0.05). In addition, the prevalence of these virulence determinants was increased in more advanced neoplasia stages (padj < 0.0125). Compared to patients with advanced colorectal adenoma and carcinoma, the ibeA gene was rarely found in the control group and among patients with non-advanced adenoma (p < 0.05), indicating its potential as the advanced-neoplasia biomarker. Patients with neoplasia frequently had E. coli strains with at least one of the abovementioned virulence factors, whereby specific combinations of these virulence factors were found.DiscussionThese findings suggest that E. coli strains isolated from patients with colorectal neoplasia possess several virulence factors, which could contribute to the development of neoplastic processes in the large intestine.

Introduction Colonic self-expanding metal stent (SEMS) placement is the preferred method for palliation of malignant colonic obstruction. We analyzed outcomes of patients who underwent colonic SEMS placement for palliation at a tertiary care oncology center in Western India. Methods Retrospective review of the endoscopy database was done for patients who underwent colonic SEMS placement at our center between January 2013 and September 2021. Demographic details, intent of stent placement, site of obstruction, length of stricture, technical success of stenting, clinical success, and complications (both immediate and long term) were noted. Results Sixty-one patients underwent colonic SEMS placement during the study period (mean age 53.6 years, 50.7% men). Obstruction was due to primary colonic malignancy in 43 (70.5%) patients and extracolonic malignancies in 18 (29.5%) patients. Most common extracolonic malignancy was gallbladder cancer in 8 (44.4%) patients. Most common site of obstruction was sigmoid colon in 18 (29.5%) patients. Proximal colonic obstruction was seen in 17 (27.9%) patients. Peritoneal metastases were seen in 26 (42.6%) patients. Colonoscopy revealed an impassable stenosis in 58 (95.1%) patients. Median length of stricture was 5 cm (range 2–9 cm). Technical success was achieved in 98.3% (60/61). Clinical success was achieved in 51 (86.4%) patients. Perforation during colonic SEMS placement was seen in 2 (3.4%) patients. Stent migration was seen in 3 (5.9%) patients, needing surgery for retrieval in all 3 patients. Over a median follow-up of 9 months (0–21 months), stent block was seen in 7 (13.7%) patients. Stent block developed after a median period of 6 months. Of these patients, three patients underwent SEMS placement within the SEMS and the other four patients underwent surgery. Conclusion Colonic SEMS placement achieves good palliation of malignant colonic obstruction in approximately 87% patients. Long-term complications like obstruction occur in a few patients after a median duration of 6 months. [ABSTRACT FROM AUTHOR]

Background: In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 µg Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT. Methods: This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals' perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening. Discussion: The aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality. Trial registration: ClinicalTrials.gov, NCT05423886, June 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05423886 [ABSTRACT FROM AUTHOR]

The incidence of colorectal cancer in people under the age of 50 (CRC<50) is increasing in the United States to the point where they will account for 12% of CRCs in 2020. A smaller increase is observed in most countries with high incomes and westernised lifestyles. In France, this phenomenon remains marginal: they represented less than 6% of CRCs in 2018. However, there is no doubt that this phenomenon will increase if it is true that the causes are essentially environmental: junk food, sedentary lifestyle, overweight and obesity being the main ones. CRC<50 have some specificities: late diagnosis, rectal and distal colonic location in 75% of cases, hereditary predisposition syndrome and/or family history of CRC present in one third of cases (Lynch syndrome in 8%). Their treatment is not specific and follows the usual recommendations. Particular attention must be paid to the consequences of the disease on fertility, sexuality and the quality of life of the survivors. Their prevention is based on the usual hygienic and dietary advice: Mediterranean diet, physical activity, fight against overweight and obesity, limiting alcohol consumption and stopping smoking. For a minority of individuals at high or very high risk, screening by colonoscopy is recommended: mainly hereditary predisposition syndromes, certain first-degree family histories of CRC and colonic localisations of inflammatory bowel diseases. For the majority of the population, there is currently no satisfactory screening strategy. Pending the advent of new biomarkers (genetic, microbial, volatile organic compounds, etc.), they should be subject to targeted, not codified screening, ideally by quantitative faecal immunochemical test, or by recto-sigmoidoscopy or colonoscopy. General practitioners and gastroenterologists should be aware and not overlook recent persistent symptoms in people under 50. [ABSTRACT FROM AUTHOR]

Background: Invasive neoplasia (Tis-T1) are increasingly being encountered in the daily routine of endoscopic polypectomy. However, the need for salvage surgery following endoscopic therapy for invasive neoplasia is controversially discussed. Patients and Methods: Patients with endoscopic removal of invasive neoplasia were identified from the national Surveillance Epidemiology and End Results (SEER) Database 2005 to 2015. Survival analysis and Cox proportional hazard regression analysis in cancer-specific mortality and overall survival rate was used, which were stratified by T stage and polyp size. Results: A total of 5805 patients with endoscopic removal of invasive neoplasia were included in the analysis, of whom 1214 (20.9%) underwent endoscopic treatment alone and 4591 (79.1%) underwent endoscopic resection plus surgery. The survival analysis revealed that patients undergoing salvage surgery had a significantly better cancer-specific survival (97.4% vs. 95.8%, p-value = 0.017). In patients with T1 stage, additional salvage surgery led to a significantly higher cancer-specific survival (92.1% vs. 95.0%, p value = 0.047). Conclusion: Salvage surgery following endoscopic polypectomy may improve the oncological survival of patients with invasive neoplasia, especially in patients with T1 stage. Furthermore, the T stage, size, and localization of polyps, as well as the level of CEA, could be identified as significant predictors for lymphonodal and distant metastases.

Background/Aims Advanced colorectal neoplasia (CRN) and significant cardiovascular disease (CVD) are very important health problems with common pathogenic mechanisms. This study sought to investigate association between the presence of advanced CRN and significant CVD through a large cohort of asymptomatic Korean individuals who voluntarily underwent colonoscopy and coronary computed tomography angiography (CCTA) as a routine health screening. Methods A total of 10,581 consecutive Korean individuals aged 20 years and older who underwent a general health examination at the Health Promotion Center of Ulsan University Hospital between January 2009 and March 2020 were retrospectively analyzed and 6,044 Subjects were included in this study after excluding ineligible participants. Advanced CRN was defined as a presence of invasive cancer or adenoma with villous component, with high-grade dysplasia, and/or a size ≥1cm. Results Study subjects with any CRN (n=1,916, 31.7%) or advanced CRN (n=240, 4.0%) had a higher mean colonary artery calcium score and a higher prevalence of various coronary plaques and significant coronary stenosis (≥50% diameter), which represent the high-risk atherosclesosis, compared to non CRN group (n=4,128, 68.3%) (all p<0.001). According to the multicariate analysis to evaluate association between CRN and CCTA findings, advanced CRN group showed an independent higher prevalence of significnat coronary stenosis (odds ratio 1.65; 95% confidence interval 1.09-2.50; p=0.019). Conclusion In asymptomatic subjects with CRN showed a higher prevalence of subclinical colonary atherosclesosis compared to non CRN group. Advanced CRN was independently associated with a significant coronary stenosis. [ABSTRACT FROM AUTHOR]

Objective: Roll-out of population-based colorectal cancer (CRC) screening with faecal immunochemical test (FIT) is limited by availability of further investigations, particularly colonoscopy and examination of excised lesions. Our objective was to assess whether variation in number of faecal samples and threshold adjustment can optimise resource utilisation and CRC detection rate. Methods: Three different screening strategies were compared for the same FIT threshold using a quantitative FIT system: one FIT, positive when > 20 µg Hb/g faeces; two FIT, positive when either was > 20 µg Hb/g faeces; and two FIT, positive when the mean was > 20 µg Hb/g faeces. We calculated changes in the size of population the provider could invite to screening for an equal number of screening positive results, and CRC and adenoma detected. Results: In our setting, Region of Murcia, south of Spain (not fully rolled out screening programme), changing the usual strategy of two FIT, positive when either to positive when the mean was > 20 µg Hb/g faeces, would increase population invited by 37.81% with the same number of positive results (which would generate a CRC detection rate of 19.2%). In a fully rolled out programme, changing the strategy from one to two FIT (positive when the mean is > 20 µg Hb/g faeces), would increase CRC detection rate by 4.64% with an increase of only 13.34% in positive FIT. Conclusions: In a population-based CRC screening programme, smart use of number of FITs and positivity threshold can increase population invited and CRC detection without increasing the number of colonoscopies and pathological examinations needed. [ABSTRACT FROM AUTHOR]

Background: Health authorities have expanded two strategies to diminish CRC-related influence: CR screening and improve diagnostic process in symptomatic patients. The aim of the current study is to design a predictive model to identify the most important risk factors that can efficiently predict patients who have high risk of colorectal neoplasia. Method: A cross-sectional study was constructed to include all patients who had positive test for FIT or had one or more risk factors for colorectal cancer based on the guidelines of detecting high-risk groups for colorectal cancer in Iran. Multivariable binary logistic regression model was constructed for prediction of colorectal neoplasia. We used sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio to check the accuracy. The Hosmer–Lemeshow test, chi-square test, and p value were used to determine the precision of model. Result: Following an AIC stepwise selection model, only nine potential variables, namely gender, watery diarrhea, IBD, abdominal pain, melena, body mass index, depression drug, anti-inflammatory drug, and age, were found to be a predictor of colorectal neoplasia. The best cut-point probability in the final model was 0.27 and results of sensitivity and specificity, based on maximizing these two criteria, were 66% and 62%, respectively. Conclusion: Overall, our model prediction was comparable with other risk prediction models for colorectal cancer. It had a modest discriminatory power to distinguish an individual's neoplasia colorectal risk. [ABSTRACT FROM AUTHOR]

Background and Aim: Randomised trials show improved polyp detection with computer-aided detection (CADe), mostly of small lesions. However, operator and selection bias may affect CADe's true benefit. Clinical outcomes of increased detection have not yet been fully elucidated., Methods: In this multicentre trial, CADe combining convolutional and recurrent neural networks was used for polyp detection. Blinded endoscopists were monitored in real time by a second observer with CADe access. CADe detections prompted reinspection. Adenoma detection rates (ADR) and polyp detection rates were measured prestudy and poststudy. Histological assessments were done by independent histopathologists. The primary outcome compared polyp detection between endoscopists and CADe., Results: In 946 patients (51.9% male, mean age 64), a total of 2141 polyps were identified, including 989 adenomas. CADe was not superior to human polyp detection (sensitivity 94.6% vs 96.0%) but outperformed them when restricted to adenomas. Unblinding led to an additional yield of 86 true positive polyp detections (1.1% ADR increase per patient; 73.8% were <5 mm). CADe also increased non-neoplastic polyp detection by an absolute value of 4.9% of the cases (1.8% increase of entire polyp load). Procedure time increased with 6.6±6.5 min (+42.6%). In 22/946 patients, the additional detection of adenomas changed surveillance intervals (2.3%), mostly by increasing the number of small adenomas beyond the cut-off., Conclusion: Even if CADe appears to be slightly more sensitive than human endoscopists, the additional gain in ADR was minimal and follow-up intervals rarely changed. Additional inspection of non-neoplastic lesions was increased, adding to the inspection and/or polypectomy workload., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale and Objectives: Microsatellite instability (MSI) stratification can guide the clinical management of patients with colorectal cancer (CRC). This study aimed to establish a radiomics model for predicting the MSI status of patients with CRC before treatment., Materials and Methods: This retrospective study was performed on 366 patients diagnosed with CRC who underwent preoperative magnetic resonance imaging (MRI) and immunohistochemical staining between February 2016 and September 2023. The participants were divided randomly into training and testing cohorts in a 7:3 ratio. The tumor volume of interest (VOI) was manually delineated on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences using 3D Slicer software, and radiomics features were extracted. Feature selection was performed using the least absolute shrinkage and selection operator method. A radiomics nomogram was developed using multiple logistic regression, and the predictive performance of the models was evaluated and compared using receiver operating characteristic curves. The calibration curve, clinical decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical application value of the model., Results: The radiomics normogram combined with history of chronic enteritis, tumor location, MR-reported inflammatory response, D2-40, carcinoembryonic antigen, tumor protein 53, and monocyte was an excellent predictive tool. The area under the curve for the training and testing cohorts were 0.927 and 0.984, respectively. The DCA and CIC demonstrated favorable clinical application and net benefit., Conclusions: A radiomics nomogram based on T2WI and ADC sequences and clinicopathologic features can effectively and noninvasively predict the MSI status in CRC. This approach helps clinicians in stratifying CRC patients and making clinical decisions for personalized treatment., Competing Interests: Declaration of Competing Interest We confirm that this article is original, has not been published elsewhere and is not currently under consideration for publication elsewhere. We have no conflicts of interest to disclose. Each author participated in the review of the manuscript, which was approved by all authors and management before submission., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Medical evidence from more recent observational studies may significantly alter our understanding of disease incidence and progression, and would require recalibration of existing computational and predictive disease models. However, it is often challenging to perform recalibration when there are a large number of model parameters to be estimated. Moreover, comparing the fitting performances of candidate parameter designs can be difficult due to significant variation in simulated outcomes under limited computational budget and long runtime, even for one simulation replication.Methods: We developed a two-phase recalibration procedure. As a proof-of-the-concept study, we verified the procedure in the context of sex-specific colorectal neoplasia development. We considered two individual-based state-transition stochastic simulation models, estimating model parameters that govern colorectal adenoma occurrence and its growth through three preclinical states: non-advanced precancerous polyp, advanced precancerous polyp, and cancerous polyp. For the calibration, we used a weighted-sum-squared error between three prevalence values reported in the literature and the corresponding simulation outcomes. In phase 1 of the calibration procedure, we first extracted the baseline parameter design from relevant studies on the same model. We then performed sampling-based searches within a proper range around the baseline design to identify the initial set of good candidate designs. In phase 2, we performed local search (e.g., the Nelder-Mead algorithm), starting from the candidate designs identified at the end of phase 1. Further, we investigated the efficiency of exploring dimensions of the parameter space sequentially based on our prior knowledge of the system dynamics.Results: The efficiency of our two-phase re-calibration procedure was first investigated with CMOST, a relatively inexpensive computational model. It was then further verified with the V/NCS model, which is much more expensive. Overall, our two-phase procedure showed a better goodness-of-fit than the straightforward employment of the Nelder-Mead algorithm, when only a limited number of simulation replications were allowed. In addition, in phase 2, performing local search along parameter space dimensions sequentially was more efficient than performing the search over all dimensions concurrently.Conclusion: The proposed two-phase re-calibration procedure is efficient at estimating parameters of computationally expensive stochastic dynamic disease models. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the most common cancers in the world. Several studies suggest using the Asia-Pacific colorectal screening (APCS) score and its modified versions to select high-risk populations for early colonoscopy, but external validation remains rare, and which score should be selected for CRC screening in China is unclear. Validation of multiple scores in the same population might help to choose the best performing score.Methods: We conducted a cross-sectional study under the framework of Cancer Screening Program in Urban China, data from asymptomatic colorectal cancer screening in Xuzhou was used to validate the APCS score, the colorectal neoplasia predict (CNP) score, the Korean colorectal screening (KCS) score, the Modified APCS score and the 8-point risk score in predicting colorectal advanced neoplasia (CAN).Results: 1804 subjects were included in the analysis and 112 CAN (6.21%) was detected. In each score, the detection rate of CAN was higher in the high-risk group than in the non-high-risk group (P < 0.05), and the RR (95%C.I.) ranged 2.20 (1.50-3.22) [8-point risk] to 4.00 (2.41-6.65) [Modified APCS]. The c-statistics (95%C.I.) of the scoring systems ranged from 0.58 (0.53-0.62) [8-point risk] to 0.65 (0.61-0.69) [KCS]. The sensitivity (95%C.I.) of these systems ranged from 31.25 (22.83-40.70) [8-point risk] to 84.82 (76.81-90.90) [Modified APCS], while the specificity (95%C.I.) ranged from 43.50 (41.12-45.90) [Modified APCS] to 83.81 (81.96-85.53) [8-point risk]. Using the APCS scoring system as a comparator, the net reclassification improvement (NRI) of each modified version ranged from - 10.34% (95%C.I.: - 22.63 to 1.95%) [8-point risk] to 4.79% (95%C.I.: - 1.50% to 11.08) [KCS]. The colonoscopy resource load (95%C.I.) ranged from 9 [1-3] [8-point risk] to 11 [3-5] [APCS and Modified APCS].Conclusions: The APCS score and its modified versions have certain ability to predict the risk of advanced neoplasia and reduce the resource load. The modified APCS score and the KCS score seemed the preferable systems to classify high risk subjects based on its high RR, sensitivity and predictive ability in the selected population. Future research could focus on adding risk factors or combining with laboratory test results to improve the predictive power of the scoring system. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic mucosal resection (EMR) is the gold standard for the treatment of noninvasive large colorectal lesions, despite challenges associated with nonlifting lesions and a high rate of local recurrence. Endoscopic submucosal dissection (ESD) offers the possibility of overcoming these EMR limitations. However, a higher risk of complications and longer procedure time prevented its dissemination. As ESD now provides more stable results because of standardized techniques compared with those used earlier, this study aimed to quantify the rates of en bloc and curative resections, as well as ESD complications, in the present situation. Methods: A multicenter, large‐scale, prospective cohort trial of ESD was conducted at 20 institutions in Japan. Consecutive patients scheduled for ESD were enrolled from February 2013 to January 2015. Results: ESD was performed for 1883 patients (1965 lesions). The mean procedure time was 80.6 min; en bloc and curative resections were achieved in 1759 (97.0%) and 1640 (90.4%) lesions, respectively, in epithelial lesions ≥20 mm. Intra‐ and postprocedural perforations occurred in 51 (2.6%) and 12 (0.6%) lesions, respectively, and emergency surgery for adverse events was performed in nine patients (0.5%). Conclusions: This trial conducted after the standardization of the ESD technique throughout Japan revealed a higher curability, shorter procedure time, and lower risk of complications than those reported previously. Considering that the target lesions of ESD are more advanced than those of EMR, ESD can be a first‐line treatment for large colorectal lesions with acceptable risk and procedure time. (Clinical Trial Registration: UMIN000010136). [ABSTRACT FROM AUTHOR]

Aim: Metabolic syndrome (MetS) is a cluster of factors including obesity, hypertension, diabetes, hypercholesterolemia and hyperlipidaemia. It has been associated with an increased risk of colorectal neoplasia. This systematic review and meta‐analysis assessed the association between MetS and (i) recurrence of adenomas or occurrence of CRC in patients with prior adenomas, and (ii) survival in patients with CRC. Method: MEDLINE, Embase, Scopus and Web of Science were searched up to 22 November 2019. Two authors independently conducted title and abstract screening; full text of eligible studies was evaluated. Where ≥3 studies reported effect measures for a specific outcome, meta‐analysis using random effects model was conducted. I2 was used to assess between‐study heterogeneity. Quality appraisal was undertaken with the Newcastle‐Ottawa Score. Results: The search identified 1,764 articles, 55 underwent full text screening, resulting in a total of 15 eligible studies. Five studies reported on metachronous neoplasia, with differing outcomes precluded a meta‐analysis. No consistent relationship between MetS and metachronous neoplasia was found. Ten studies reported on survival outcomes. MetS was associated with poorer CRC‐specific survival (HR = 1.8, 95% CI: 1.04–3.12, I2 = 92.7%, n = 3). Progression‐free survival was also worse but this did not reach statistical significance (HR = 1.12, 95% CI: 0.89–1.42, I2 = 85.6%, n = 3). There was no association with overall survival (HR = 1.04, 95% CI: 0.94–1.15, I2 = 43.7%, n = 7). Significant heterogeneity was present but subgroup analysis did not account for this. Conclusion: MetS is associated with poorer CRC‐specific survival, but evidence is inconsistent on metachronous neoplasia. Further research is warranted to better understand the impact of MetS on the adenoma‐carcinoma pathway. [ABSTRACT FROM AUTHOR]

Background: Colon capsule endoscopy (CCE) is an alternative for patients unwilling or with contraindications for conventional colonoscopy. Colorectal cancer screening may benefit greatly from widespread acceptance of a non-invasive tool such as CCE. However, reviewing CCE exams is a time-consuming process, with risk of overlooking important lesions. We aimed to develop an artificial intelligence (AI) algorithm using a convolutional neural network (CNN) architecture for automatic detection of colonic protruding lesions in CCE images. An anonymized database of CCE images collected from a total of 124 patients was used. This database included images of patients with colonic protruding lesions or patients with normal colonic mucosa or with other pathologic findings. A total of 5715 images were extracted for CNN development. Two image datasets were created and used for training and validation of the CNN. The AUROC for detection of protruding lesions was 0.99. The sensitivity, specificity, PPV and NPV were 90.0%, 99.1%, 98.6% and 93.2%, respectively. The overall accuracy of the network was 95.3%. The developed deep learning algorithm accurately detected protruding lesions in CCE images. The introduction of AI technology to CCE may increase its diagnostic accuracy and acceptance for screening of colorectal neoplasia. [ABSTRACT FROM AUTHOR]

Purpose of review: We aimed to determine whether young-onset adenomas increased the risk for colorectal cancer by determining the adenoma prevalence, risk factors associated with young-onset adenomas, as well as the need for surveillance colonoscopies in the young-adult population (age < 50). Recent findings: By examining multiple meta-analyses and systematic review studies, we determined that while adenoma rates are lower in young adults (age < 45) compared to those > age 50, subsets of young adults are at higher risk of adenoma formation and therefore may have increased colorectal cancer risk. Therefore, surveillance colonoscopy may be beneficial for patients aged 40–49 years of age to reduce colorectal cancer risk, particularly in young-adult patients presenting with concerning symptoms, such as bright red blood per rectum, those found to have high-risk advanced adenomas, and those with risk factors associated with higher adenoma detection rates including diabetes, male gender, and metabolic syndrome. Summary: Young adults found to have adenomas may warrant both close surveillance with colonoscopy as well as hereditary cancer risk assessment and genetic testing to identify underlying hereditary cancer syndromes. [ABSTRACT FROM AUTHOR]

Background: Invasive neoplasia (Tis-T1) are increasingly being encountered in the daily routine of endoscopic polypectomy. However, the need for salvage surgery following endoscopic therapy for invasive neoplasia is controversially discussed. Patients and Methods: Patients with endoscopic removal of invasive neoplasia were identified from the national Surveillance Epidemiology and End Results (SEER) Database 2005 to 2015. Survival analysis and Cox proportional hazard regression analysis in cancer-specific mortality and overall survival rate was used, which were stratified by T stage and polyp size. Results: A total of 5805 patients with endoscopic removal of invasive neoplasia were included in the analysis, of whom 1214 (20.9%) underwent endoscopic treatment alone and 4591 (79.1%) underwent endoscopic resection plus surgery. The survival analysis revealed that patients undergoing salvage surgery had a significantly better cancer-specific survival (97.4% vs. 95.8%, p-value = 0.017). In patients with T1 stage, additional salvage surgery led to a significantly higher cancer-specific survival (92.1% vs. 95.0%, p value = 0.047). Conclusion: Salvage surgery following endoscopic polypectomy may improve the oncological survival of patients with invasive neoplasia, especially in patients with T1 stage. Furthermore, the T stage, size, and localization of polyps, as well as the level of CEA, could be identified as significant predictors for lymphonodal and distant metastases. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at assessing the effect of chemotherapy on dietary intake and nutritional status of patients with colorectal cancer undergoing chemotherapy. Methods: Observational, cross-sectional study conducted with 35 patients of both sexes, aged 50 years or older. Dietary intake was assessed four times: before (T0), twice during (T1 and T2), and after (TF) chemotherapy. Data on energy, macronutrients, and micronutrients were used for assessing dietary intake. Nutritional status was assessed on the first day and at the end of the chemotherapy cycle. The data were treated statistically using a 5% significance level. Results: The intake of energy, carbohydrates, lipids, selenium, and iron was lower after chemotherapy infusion (p < 0.05). Energy consumption decreased when comparing T0 (1419.8 ± 527.1 kcal) with T1 (1181.9 ± 423.2 kcal). Regarding macronutrients, carbohydrates and lipids showed a drop (p < 0.05), but there were no differences in protein intake, and it was observed that the consumption of food sources such as dairy was prioritized. In the analysis of vitamins and minerals, vitamins dropped but without a significant difference. There were significant differences between T1 and TF for iron (9.7 mg ± 4.5 mg and 12.0 ± 4.0 mg) and selenium (77.4 ± 29.7 µg and 93.6 ± 37.8 µg). There was no change in body composition and nutritional status between chemotherapy cycles. Conclusion: The treatment reduced patients' food consumption after the chemotherapy session and impacted dietary intake, which demonstrates the importance of nutritional counseling and intervention, especially on energy consumption. [ABSTRACT FROM AUTHOR]

Alteration of the gut virome has been associated with colorectal cancer (CRC); however, when and how the alteration takes place has not been studied. Here, we employ a longitudinal study in mice to characterize the gut virome alteration in azoxymethane (AOM)-induced colorectal neoplasia and identify important viruses associated with tumor growth. The number and size of the tumors increased as the mice aged in the AOM treated group, as compared to the control group. Tumors were first observed in the AOM group at week 12. We observed a significantly lower alpha diversity and shift in viral profile when tumors first appeared. In addition, we identified novel viruses from the genera Brunovirus, Hpunavirus that are positively associated with tumor growth and enriched at a late time point in AOM group, whereas members from Lubbockvirus show a negative correlation with tumor growth. Moreover, network analysis revealed two clusters of viruses in the AOM virome, a group that is positively correlated with tumor growth and another that is negatively correlated with tumor growth, all of which are bacteriophages. Our findings suggest that the gut virome changes along with tumor formation and provides strong evidence of a potential role for bacteriophage in the development of colorectal neoplasia. [ABSTRACT FROM AUTHOR]

Abstract Background Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions. Methods This prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power. Discussion TC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy. Trial registration Clinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/show/NCT04180033 .