Unique electrophysiological property of a novel Nav1.7, Nav1.8, and Nav1.9 sodium channel blocker, ANP-230.

Voltage-gated sodium channel subtypes, Nav1.7, Nav1.8, and Nav1.9 are predominantly expressed in peripheral sensory neurons. Recent genetic studies have revealed that they are involved in pathological pain processing and that the blockade of Nav1.7, Nav1.8, or Nav1.9 will become a promising pharmacotherapy especially for neuropathic pain. A growing number of drug discovery programs have targeted either of the subtypes to obtain a selective inhibitor which can provide pain relief without affecting the cardiovascular and central nervous systems, though none of them has been approved yet. Here we describe the in vitro characteristics of ANP-230, a novel sodium channel blocker under clinical development. Surprisingly, ANP-230 was shown to block three pain-related subtypes, human Nav1.7, Nav1.8, and Nav1.9 with similar potency, but had only low inhibitory activity to human cardiac Nav1.5 channel and rat central Nav channels. The voltage clamp experiments using different step pulse protocols revealed that ANP-230 had a "tonic block" mode of action without state- and use-dependency. In addition, ANP-230 caused a depolarizing shift of the activation curve and decelerated gating kinetics in human Nav1.7-stably expressing cells. The depolarizing shift of activation curve was commonly observed in human Nav1.8-stably expressing cells as well as rat dorsal root ganglion neurons. These data suggested a quite unique mechanism of Nav channel inhibition by ANP-230. Finally, ANP-230 reduced excitability of rat dorsal root ganglion neurons in a concentration dependent manner. Collectively, these promising results indicate that ANP-230 could be a potent drug for neuropathic pain.

Diagnostic performance of deep-learning-based virtual chromoendoscopy in gastric neoplasms.

BACKGROUNDS: Cycle-consistent generative adversarial network (CycleGAN) is a deep neural network model that performs image-to-image translations. We generated virtual indigo carmine (IC) chromoendoscopy images of gastric neoplasms using CycleGAN and compared their diagnostic performance with that of white light endoscopy (WLE). METHODS: WLE and IC images of 176 patients with gastric neoplasms who underwent endoscopic resection were obtained. We used 1,633 images (911 WLE and 722 IC) of 146 cases in the training dataset to develop virtual IC images using CycleGAN. The remaining 30 WLE images were translated into 30 virtual IC images using the trained CycleGAN and used for validation. The lesion borders were evaluated by 118 endoscopists from 22 institutions using the 60 paired virtual IC and WLE images. The lesion area concordance rate and successful whole-lesion diagnosis were compared. RESULTS: The lesion area concordance rate based on the pathological diagnosis in virtual IC was lower than in WLE (44.1% vs. 48.5%, p < 0.01). The successful whole-lesion diagnosis was higher in the virtual IC than in WLE images; however, the difference was insignificant (28.2% vs. 26.4%, p = 0.11). Conversely, subgroup analyses revealed a significantly higher diagnosis in virtual IC than in WLE for depressed morphology (41.9% vs. 36.9%, p = 0.02), differentiated histology (27.6% vs. 24.8%, p = 0.02), smaller lesion size (42.3% vs. 38.3%, p = 0.01), and assessed by expert endoscopists (27.3% vs. 23.6%, p = 0.03). CONCLUSIONS: The diagnostic ability of virtual IC was higher for some lesions, but not completely superior to that of WLE. Adjustments are required to improve the imaging system's performance.

A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

BACKGROUND: The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). METHODS: EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50 years) and intervals (2/5/10 years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. RESULTS: Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45 years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20 mm in size, and the deep submucosal invasion rate was less than 30%. CONCLUSIONS: A mathematical simulation model revealed that screening every 5 years starting at 45 years of age could efficiently assist in identifying HpNGNs at an early stage.

Cost-effectiveness analysis of single colonoscopy versus single fecal test for colorectal cancer diagnosis and treatment.

BACKGROUND AND AIM: Regular endoscopy or fecal immunochemical test (FIT) is ideal for screening colorectal cancer. However, only a limited number of individuals undergo regular screening. This study aimed to compare the cost-effectiveness of a single colonoscopy with a single FIT performed for colorectal cancer screening. METHODS: A microsimulation model was constructed based on real-world observational data collected from three institutions between 2019 and 2022 that compared colonoscopy-based screening with FIT-based screening. The total costs of diagnosis and treatment of the detected lesions using the two strategies were calculated. The incremental cost-effectiveness ratio (ICER) per life year gained (LYG) of the colonoscopy-based strategy was calculated. RESULTS: Data from 11 407 patients undergoing colonoscopies and 59 176 patients undergoing FITs were used to establish a model. In the base case analysis of screening strategies, colonoscopy was more cost-effective than FIT (ICER 415 193 yen/LYG). The ICER of the colonoscopy-based strategy among 60- to 69-year-old patients was lowest at 394 200 yen/LYG, whereas that in 20- to 29-year-old patients was highest. Monte Carlo simulations showed that the colonoscopy-based strategy was more cost-effective than the FIT-based strategy (net monetary benefit [NMB]: 5 695 957 yen vs 5 348 253 yen). When the adenoma detection rate in the colonoscopy was over 30% or the positive FIT rate was lower than 8.6% in the FIT-based strategy, the NMB of the colonoscopy-based strategy exceeded that of the FIT-based strategy. CONCLUSION: In the microsimulation model, colonoscopy is recommended as a one-time screening procedure in patients aged >60 years with >30% ADR or <8.6% positive FIT rate.

A Close Follow-Up Strategy in the Short Period of Time after Helicobacter pylori Eradication Contributes to Earlier Detection of Gastric Cancer.

INTRODUCTION: The purpose of this study was to optimize the surveillance frequency and period for efficient detection of early gastric cancer (EGC) after Helicobacter pylori (HP) eradication. METHODS: Data from patients with eradicated HP infection were extracted from the endoscopy databases of two institutions from January 2016 to March 2021. The patients were divided into a close follow-up group with frequent surveillance after eradication and an open follow-up group with an intermittent surveillance method, and the cases of post-eradication EGC found in the two groups were analyzed. RESULTS: Thirty-six out of 9,322 patients (0.39%) in the close follow-up group and 20 out of 11,436 patients (0.17%) in the open follow-up group were found to have EGC. The cumulative incidence of EGC after eradication was significantly higher in the close follow-up group (p = 0.004). The duration between eradication and EGC detection was significantly shorter in the close follow-up group (51.7 vs. 90.5 months, p = 0.002). A logistic regression model revealed that duration after eradication was an independent predictor for detecting EGC in the close follow-up group (p = 0.045). A Cox proportional hazards model revealed that the close follow-up strategy was effective in patients with an eradication duration of less than 65 months to identify EGC (p = 0.015), but there was no difference between the two strategies in patients with an eradication duration of more than 65 months (p = 0.624). DISCUSSION/CONCLUSIONS: Frequent surveillance after HP eradication is efficient for the early detection of EGC during the first 65 months.

Colorectal cold snare polypectomy: Current standard technique and future perspectives.

It has been shown that resection of adenomatous colorectal polyps can reduce mortality due to colorectal cancer. In daily clinical practice, simpler and safer methods of colorectal polypectomy have been sought to enable endoscopists to resect all detected lesions. Among these, cold snare polypectomy (CSP) is widely used in clinical practice because of its advantages in shortening procedure time, reducing delayed bleeding risk, and lowering treatment costs, while maintaining a similar complete resection rate for lesions smaller than 10 mm when compared to conventional hot snare polypectomy. This review introduces the findings of previous studies that investigated the efficacy and safety of the CSP procedure for nonpedunculated polyps smaller than 10 mm, and describes technical points to remember when practicing CSP based on the latest evidence, including using a thin wire snare specifically designed for CSP, and observing the surrounding mucosa of the resection site with chromoendoscopy or image-enhanced endoscopy to ensure that there is no residual lesion. This review also describes the potential of expanding the indication of CSP as a treatment for lesions larger than 10 mm, those with pedunculated morphology, those located near the appendiceal orifice, and for patients under continuous antithrombotic agent therapy. Finally, the perspective on optimal treatments for recurrent lesions after CSP is also discussed, despite the limited related evidence and data.

A delay in the diagnosis of colorectal cancer screened by fecal immunochemical tests during the COVID-19 pandemic: a longitudinal cohort study.

PURPOSE: There is concern that the COVID-19 pandemic may cause people to refrain from undergoing examination resulting in delayed detection of colorectal cancer (CRC). The purpose of this study was to investigate whether there was a delay in CRC detection due to withholding of screening. METHODS: The colonoscopy screening rate and the CRC detection rate were calculated for patients who underwent fecal immunochemical tests (FITs) from 2018 to 2021 in the longitudinal cohort. The stages of CRC cases detected as a result of positive FIT in each year were compared. RESULTS: A total of 39,521 patients were initially screened by FIT over a 4-year period. The FIT-positive rate was 4.7% (441 /9,349) in 2018, 4.6% (420 /9,156) in 2019, 4.9% (453 /9,255) in 2020, and 4.3% (504 /11,760) in 2021. The colonoscopy screening rate for positive FIT results was lower in 2020 than in 2019 (25.8% vs. 38.1%, P < 0.001), and higher in 2021 than in 2020 (56.7% vs. 25.8%, P < 0.001). The CRC detection rate among colonoscopy recipients was higher in 2021 than in 2020 (13% vs. 4%, P = 0.014). Stage 1 or higher CRC accounted for 25.0% (1/4) in 2020, and 78% (18/23) in 2021. Among the CRC cases detected each year, 1 (14%), 1 (25%), and 10 (43%) did not undergo colonoscopy despite positive FIT results in the previous year. CONCLUSIONS: The COVID-19 pandemic has reduced the detection of CRC by screening colonoscopy following FIT and might have led to a delay in the detection of CRC.

Pre-administration of super-low volume polyethylene glycol is as effective as senna laxative as bowel preparation for colonoscopy: a randomized controlled phase 2 trial.

BACKGROUND AND PURPOSE: Senna laxatives are commonly used for bowel preparation before colonoscopies in Japan. However, this laxative frequently causes complications such as abdominal pain. This study aimed to establish a novel method of bowel preparation, which involved the pre-administration of super-low volume polyethylene glycol (PEG) for three days followed by the same-day administration of low volume PEG. METHODS: This study was a prospective, multicenter, investigator-blinded, phase 2, randomized control trial. The intake of 13.9 g (120 mL) of PEG or 1 g of a senna laxative for 3 days before the examination was indicated for each group, and 2 L of PEG solution was used for preparation on the examination day. The primary endpoint was the efficacy of bowel cleansing, as assessed by the Boston bowel preparation scale. The secondary endpoints were the adenoma detection rate and occurrence of complications. RESULTS: A total of 250 patients were initially enrolled. A total of 122 patients from each group were included in the intention-to-treat analysis. In the intention-to-treat analysis, the responder rates were the same for the two groups (56.6% vs 50.8%). Additionally, the adenoma detection rate did not differ between the two groups (34.9% vs 41.8%, P = 0.3795). In contrast, adherence was higher in the PEG group (93.4% vs 82.8%, P = 0.0101), and the occurrence of complications was lower in the PEG group (1.7% vs 16.4%, P = 0.0001). CONCLUSION: The novel super-low volume PEG method for bowel preparation was as effective as the conventional method with senna laxatives.

Individual feedback and monitoring of endoscopist performance improves the adenoma detection rate in screening colonoscopy: a prospective case-control study.

BACKGROUND AND PURPOSE: Previous reports have suggested that a longer withdrawal time (WT) during colonoscopy led to an improved adenoma detection rate (ADR); however, there are few controlled studies that substantiated monitoring WT as an educational method. We aimed to validate a feedback and monitoring system to improve the ADR in screening colonoscopy in a prospective case-control setting. METHODS: After collecting data in the pre-feedback period (3.5 months), the individual performance and the average ADR and WT values of the facility were provided to 6 endoscopists in the intervention group, while 3 endoscopists were isolated as the control group during the feedback period (2 weeks). The intervention group consisted of two subgroups, the Fast and Slow WT groups, according to the results from the pre-feedback period. The endoscopists in the intervention group were instructed to be aware of their own WT in each examination during the post-feedback period (4 months). The performances of all endoscopists in the post-feedback period were analyzed and compared with those in the pre-feedback period. RESULTS: Among the initial analyses, the correlation analysis and multivariate analysis revealed that WT was an independent predictor for the ADR (P = 0.0101). After providing individual performance feedback and instruction regarding real-time WT monitoring, the WT was significantly prolonged in the Fast WT group (P = 0.0346) but did not change in the Slow WT and control groups. In addition, the ADR of the Fast WT group significantly improved after the intervention (P = 0.024), whereas the ADR of the Slow WT and control groups did not change. CONCLUSION: Providing individual feedback on ADR and WT and monitoring WT helped improve the endoscopists' ADRs.

Indispensable role of Notch ligand-dependent signaling in the proliferation and stem cell niche maintenance of APC-deficient intestinal tumors.

Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5+ve cells of APC-deficient mice intestinal tumors. Accordingly, Notch ligands, including Jag1, Dll1, and Dll4, were expressed in these tumors. In vitro studies using tumor-derived organoids confirmed the intrinsic Notch activity-dependent growth of tumor cells. Surprisingly, the targeted deletion of Jag1 but not RBPJ in LGR5+ve tumor-initiating cells resulted in the silencing of Hes1 expression, disruption of the tumor stem cell niche, and dramatic reduction in the proliferation activity of APC-deficient intestinal tumors in vivo. Thus, our results highlight the importance of ligand-dependent non-canonical Notch signaling in the proliferation and maintenance of the tumor stem cell niche in APC-deficient intestinal adenomas.

[Stem Cell System. The intestinal stem cell system.]

The intestinal epithelium harbors stem cells at the bottom of crypts. Intestinal stem cells(ISCs)differentiate toward two alternative lineages of secretory or absorptive cells in a unidirectional manner. Studies have revealed factors that are indispensable for maintaining proliferation and differentiation of ISCs, which are provided from the surrounding environment. Additionally, several back-up systems compensating the sudden and massive loss of the ISC pool has been reported. Recent development of the three-dimensional culture system of ISCs in vitro has greatly contributed to elucidate these functional analyses of ISCs.

An algorithm-based active cleansing protocol can reduce the bowel preparation time for screening colonoscopy: A propensity score matching study.

BACKGROUND: Methods that minimize the time for on-site bowel preparation before colonoscopy are needed. We prospectively validated that a novel algorithm-based active cleansing (ABAC) protocol could reduce the time for preparation compared with the conventional method. METHODS: This was an open-label, multicenter, prospective comparative study from April to October 2021. The study compared the bowel preparation time for colonoscopy between patients instructed with the ABAC protocol and control groups. Patients in the ABAC protocol group as well as the control group were administered 2000 mL of polyethylene glycol (PEG) within 2 hours. After the first two hours, patients in the protocol group voluntarily took 300 ml of the solution without the instruction of nursing staff depending on the number of defecations in the first 2 hours. The intervention and control groups were adjusted for background characteristics by propensity score matching (PSM). RESULTS: After adjustment by PSM, 174 patients in each of the two groups were included in the final analysis. In the intention-to-treat analysis, the preparation time was significantly shorter in the intervention group than that in the control group (126.3 ± 32.7 min vs. 144.9 ± 39.9 min, P = 0.018). The proportion of additional PEG intake was significantly higher in the intervention group (16 [9.2%] vs. 6 [3.4%], P = 0.047). The number of defecations was also higher in the intervention group than in the control group (7.8 ± 2.5 vs. 6.3 ± 2.2, P = 0.001). CONCLUSIONS: Simple active instruction protocol is effective to reduce on-site bowel preparation time and nursing staff labor for colonoscopy.

Red dichromatic imaging and linked color imaging as reliable image-enhanced endoscopic procedures for detecting the distal end of the palisade vessels in the columnar metaplastic mucosa of the gastroesophageal junction zone.

BACKGROUND: There is a consensus that identifying the distal end of the palisade vessels (DEPV) is important for diagnosing gastroesophageal junction (GEJ). However, optimum observation methods have not been established. This study investigated the use of effective image-enhanced endoscopy (IEE) for DEPV detection. METHODS: One hundred endoscopic images in 20 cases of columnar metaplastic mucosa of the GEJ recorded with white-light imaging (Olympus-WLI and Fujifilm-WLI) and IEEs (narrow-band imaging; RDI1/2/3, red dichromatic imaging; texture and color enhancement imaging 1/2; blue-laser imaging; and LCI, linked color imaging) from two manufacturers were extracted and evaluated by 10 evaluators. Up to 24 radial straight lines from the center of the lumen were placed on the image, and the evaluators placed markings according to confidence level (high, low, and not detectable) at the DEPV locations. The detectability and reproducibility at the rate of the confidence level and coefficient of variance of markings among the evaluator were analyzed. RESULTS: In total, 15,180 markings were obtained. In terms of detectability, RDI1 (49.4%), RDI2 (53.0%), RDI3 (54.1%), TXI2 (49.7%), and LCI (34.6%) had a significantly higher rate of high confidence among the IEEs in each manufacturer. By contrast, Olympus-WLI (40.6%), Fujifilm-WLI (17.6%), narrow-band imaging (15.9%), and blue laser imaging (9.8%) presented with a significantly lower rates of high confidence. Regarding reproducibility, RDI3 and LCI had the lowest coefficient of variance for each manufacturer. CONCLUSIONS: RDI and LCI could be reliable modalities for detecting DEPVs in the columnar metaplastic mucosa of the GEJ zone.

Optimizing Helicobacter pylori Treatment: An Updated Review of Empirical and Susceptibility Test-Based Treatments.

As the rate of discovery of drug-resistant Helicobacter pylori cases increases worldwide, the relevant societies have updated their guidelines for primary eradication regimens. A promising strategy against drug-resistant H. pylori is tailored therapy based on the results of an antibiotic susceptibility test; however, it is difficult to apply this strategy to all cases. Although culture-based antibiotic susceptibility tests can assess resistance to any antimicrobial agent, their greatest disadvantage is the time required to draw a conclusion. In contrast, molecular-based methods, such as polymerase chain reaction, can rapidly determine the presence of resistance, although a single test can only test for one type of antimicrobial agent. Additionally, the limited availability of facilities for molecular-based methods has hindered their widespread use. Therefore, low-cost, minimally invasive, simple, and effective primary regimens are needed. Several studies have compared the efficacy of the latest primary eradication regimens against that of tailored therapies, and their results have shaped guidelines. This article reviews the latest research on empirical and tailored treatments for H. pylori infections. Evidence for the superiority of tailored therapy over empirical therapy is still limited and varies by region and treatment regimen. A network meta-analysis comparing different empirical treatment regimens showed that vonoprazan triple therapy provides a superior eradication effect. Recently, favorable results towards vonoprazan dual therapy have been reported, as it reached eradication levels similar to those of vonoprazan triple therapy. Both vonoprazan dual therapy and tailored therapy based on antibiotic susceptibility tests could contribute to future treatment strategies.

Utility of Indices Obtained during Medical Checkups for Predicting Fatty Liver Disease in Non-obese People.

Objective To predict fatty liver disease (FLD), including nonalcoholic FLD (NAFLD) and metabolic dysfunction-associated FLD (MAFLD), from blood tests and anthropometric measurements, the fatty liver index (FLI) and triglyceride glucose-body mass index (TyG-BMI) have been reported as promising indicators. We evaluated the predictive ability of several indices, including the waist circumference, BMI, FLI and TyG-BMI, that might predict FLD in non-obese individuals undergoing health checkups. Methods This retrospective observational study enrolled non-obese subjects who underwent abdominal ultrasonography between May 1, 2015, and June 30, 2022. Obesity was defined as a BMI <25 kg/m2. FLD was diagnosed by abdominal ultrasonography. Using a receiver operating characteristic analysis, we examined the predictive validity of indices for NAFLD and MAFLD by calculating the area under the curve (AUC). Results Of the 24,825 subjects (mean age 44.3±10.0 years old; 54% men) enrolled in this examination of the association of indices, including FLI and TyG-BMI, with NAFLD, NAFLD was diagnosed in 3,619 (27%) men and 733 (6%) women. In both men and women, the FLI and TyG-BMI had significantly higher AUC values for NAFLD prediction than the other indicators (FLI: 0.786 for men and 0.875 for women, TyG-BMI: 0.783 for men and 0.868 for women). In analyses of subjects with a BMI <23 kg/m2, the superiority of the FLI and TyG-BMI remained unchanged. The FLI and TyG-BMI also had significantly higher AUC values for MAFLD prediction than the other indicators. Conclusion The FLI and TyG-BMI had a particularly high predictive ability for NAFLD and MAFLD in non-obese subjects.

Exploring quality indicators for the detection of Helicobacter pylori-naïve gastric cancer: a cross-sectional nationwide survey.

BACKGROUND/AIMS: Diagnosis of Helicobacter pylori-naïve gastric cancer (HPNGC) is becoming increasingly important. This study aimed to explore the quality indicators for HPNGC detection. METHODS: We conducted a cross-sectional, nationwide, web-based survey of gastrointestinal endoscopists in Japan. In addition to questions about the number of HPNGC cases detected in a year and basic information, the questionnaire also consisted of 28 questions: (1) 18 about HPNGC awareness, (2) six about diagnostic proactiveness, and (3) four about interest in HPNGC. RESULTS: Valid responses were obtained from 712 endoscopists. The Japan Gastroenterological Endoscopy Society-certified endoscopists had a significantly higher HPNGC detection rate than the nonspecialists (0.42% vs. 0.32%, respectively; p=0.008). The results of the multiple regression analysis showed that Japan Gastroenterological Endoscopy Society certification and high awareness and interest scores were independent predictors of the HPNGC detection rate (p=0.012, p<0.001, p=0.024, respectively). Principal component analysis showed that the endoscopists who attended conferences for collecting information on HPNGC had a higher level of awareness. CONCLUSION: To improve the detection of HPNGC, it is necessary to increase the awareness of the disease. It is hoped that relevant societies will play an important role in endoscopists' education.

Detecting colorectal lesions with image-enhanced endoscopy: an updated review from clinical trials.

Colonoscopy plays an important role in reducing the incidence and mortality of colorectal cancer by detecting adenomas and other precancerous lesions. Image-enhanced endoscopy (IEE) increases lesion visibility by enhancing the microstructure, blood vessels, and mucosal surface color, resulting in the detection of colorectal lesions. In recent years, various IEE techniques have been used in clinical practice, each with its unique characteristics. Numerous studies have reported the effectiveness of IEE in the detection of colorectal lesions. IEEs can be divided into two broad categories according to the nature of the image: images constructed using narrowband wavelength light, such as narrowband imaging and blue laser imaging/blue light imaging, or color images based on white light, such as linked color imaging, texture and color enhancement imaging, and i-scan. Conversely, artificial intelligence (AI) systems, such as computer-aided diagnosis systems, have recently been developed to assist endoscopists in detecting colorectal lesions during colonoscopy. To better understand the features of each IEE, this review presents the effectiveness of each type of IEE and their combination with AI for colorectal lesion detection by referencing the latest research data.

Dietary restriction after cold snare polypectomy of colorectal polyp for prevention of delayed bleeding.

Background and Aim: Cold snare polypectomy (CSP) for small colorectal polyps is a safe technique; however, there is little evidence on whether dietary restriction after CSP is essential. This study aimed to determine whether dietary restriction after CSP is necessary to prevent delayed bleeding. Methods: This is a randomized, controlled, non-inferiority trial conducted between November 2021 and March 2022. Patients with non-pedunculated small colorectal polyps (<10 mm) and who did not take anticoagulants were randomly allocated to two groups: (i) the normal diet (ND) group, and (ii) the low-residue diet (LRD) group. The ND group was instructed to eat anything after CSP, whereas the LRD group was advised to take LRD for 3 days after CSP. The primary endpoint was the occurrence of delayed major bleeding that needed endoscopic hemostasis. Results: A total of 193 patients (average 57.5 years old, 51.9% male) were enrolled in the study. Subsequently, 97 and 96 patients were allocated to the ND and LRD group, respectively. The occurrence of delayed major bleeding was 1.0% in the ND group and 2.1% in the LRD group (95% confidence interval [CI]: -4.4% to 2.4%; difference: -1.1%), which showed the non-inferiority of the ND group. In addition, there was no difference between the two groups with respect to the occurrence of minor delayed bleeding (3.1% and 4.2%, respectively; difference: -1.1% [95% CI: -6.4% to 4.2%]). Conclusion: Dietary restriction after CSP for low-bleeding-risk colorectal polyps is not necessary for the prevention of delayed bleeding (Registration number: UMIN000045669).