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Background and Aim: Tip‐in endoscopic mucosal resection (EMR) has a high en bloc resection rate for large colorectal neoplasms. However, non‐experts' performance in Tip‐in EMR has not been investigated. We investigated whether Tip‐in EMR can be achieved effectively and safely even by non‐experts. Methods: This retrospective study included consecutive patients who underwent Tip‐in EMR for 15–25 mm colorectal nonpedunculated neoplasms at a Japanese tertiary cancer center between January 2014 and December 2020. Baseline characteristics, treatment outcomes, learning curve of non‐experts, and risk factors of failing self‐achieved en bloc resection were analyzed. Results: A total of 597 lesions were analyzed (438 by experts and 159 by non‐experts). The self‐achieved en bloc resection (69.8% vs 88.6%, P < 0.001) and self‐achieved R0 resection (58.3% vs 76.5%, P < 0.001) rates were significantly lower in non‐experts with <10 cases of experience than in experts, but not in non‐experts with >10 cases. Adverse event (P = 0.165) and local recurrence (P = 0.892) rates were not significantly different between experts and non‐experts. Risk factors of failing self‐achieved en bloc resection were non‐polypoid morphology (OR 3.4, 95% CI 1.6–7.3, P = 0.001), lesions with an underlying semilunar fold (OR 3.6, 95% CI 1.6–7.3, P < 0.001), positive non‐lifting sign (OR 3.1, 95% CI 1.2–8.0, P = 0.023), and non‐experts with an experience of ≤10 cases (OR 3.6, 95% CI 2.1–6.3, P < 0.001). Conclusion: The clinical outcomes of Tip‐in EMR for 15–25 mm lesions performed by non‐experts were favorable. [ABSTRACT FROM AUTHOR]

Flow cytometry can provide detailed information about protein expression on cell surface and is, therefore, widely used in clinical testing. However, owing to the limited sensitivity of fluorescence signals, detection of low‐expression cell surface markers is challenging. The present report describes a DNA‐mediated, on‐membrane assembly of conjugated polymer nanoparticles (Pdots) that amplifies fluorescence signal from surface markers for sensitive detection via flow cytometry. Single‐stranded DNA (ssDNA)‐conjugated antibodies are first bound to cell surface markers, from which ssDNA‐modified Pdots are sequentially assembled using DNA hybridization. The use of DNA as a linker enables the distance‐controlled assembly of Pdots to prevent fluorescence quenching, whereas their on‐membrane sequential assembly allows amplification of the fluorescence signal without reducing binding ability of antibodies. Thus, two rounds of Pdot assembly achieve 31‐fold amplification of the fluorescence signal from CD19 on Nalm‐6 cells, which is 125‐fold brighter than that obtained using the conventional fluorescent dye‐based method. Moreover, the sequential assembly of 22 nm Pdots shows 24‐fold higher fluorescence than one‐step labeling with 81 nm Pdots, suggesting the advantage of the sequential assembly strategy in avoiding steric hindrance. The proposed method is expected to contribute to the sensitive detection of low‐expression surface markers for early and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Computer‐aided detection (CADe) systems can efficiently detect polyps during colonoscopy. However, false‐positive (FP) activation is a major limitation of CADe. We aimed to compare the rate and causes of FP using CADe before and after an update designed to reduce FP. Methods: We analyzed CADe‐assisted colonoscopy videos recorded between July 2022 and October 2022. The number and causes of FPs and excessive time spent by the endoscopist on FP (ET) were compared pre‐ and post‐update using 1:1 propensity score matching. Results: During the study period, 191 colonoscopy videos (94 and 97 in the pre‐ and post‐update groups, respectively) were recorded. Propensity score matching resulted in 146 videos (73 in each group). The mean number of FPs and median ET per colonoscopy were significantly lower in the post‐update group than those in the pre‐update group (4.2 ± 3.7 vs 18.1 ± 11.1; P < 0.001 and 0 vs 16 s; P < 0.001, respectively). Mucosal tags, bubbles, and folds had the strongest association with decreased FP post‐update (pre‐update vs post‐update: 4.3 ± 3.6 vs 0.4 ± 0.8, 0.32 ± 0.70 vs 0.04 ± 0.20, and 8.6 ± 6.7 vs 1.6 ± 1.7, respectively). There was no significant decrease in the true positive rate (post‐update vs pre‐update: 95.0% vs 99.2%; P = 0.09) or the adenoma detection rate (post‐update vs pre‐update: 52.1% vs 49.3%; P = 0.87). Conclusions: The updated CADe can reduce FP without impairing polyp detection. A reduction in FP may help relieve the burden on endoscopists. [ABSTRACT FROM AUTHOR]

Background and Aim: Hot snare polypectomy using blend or coagulation current is widely used; however, it causes deeper tissue heat injury, leading to adverse events. We hypothesized that hot polypectomy using low‐power pure cut current (PureCut, effect 1 10 W) could reduce deeper tissue heat injury. We conducted animal experiments to evaluate the deeper tissue heat injury and conducted a prospective clinical study to examine its cutting ability. Methods: In a porcine rectum, hot polypectomy using Blend current (EndoCut, effect 3 40 W) and low‐power pure cut current was performed. The deepest part of heat destruction and thickness of the non‐burned submucosal layer were evaluated histologically. Based on the results, we performed low‐power pure cut current hot polypectomy for 10–14 mm adenoma. The primary endpoint was complete resection defined as one‐piece resection with negative for adenoma in quadrant biopsies from the defect margin. Results: In experiments, all low‐power pure‐cut resections were limited within the submucosal layer whereas blend current resections coagulated the muscular layer in 13% (3/23). The remaining submucosal layer was thicker in low‐power pure cut current than in blend current resections. In the clinical study, low‐power pure‐cut hot polypectomy removed all 100 enrolled polyps. For 98 pathologically neoplastic polyps, complete resection was achieved in 84 (85.7%, 95% confidence interval, 77–92%). The lower limit of the 95% confidence interval was not more than 15% below the pre‐defined threshold of 86.6%. No severe adverse events occurred. Conclusions: A novel low‐power pure‐cut hot polypectomy may be feasible for adenoma measuring 10–14 mm. (UMIN000037678). [ABSTRACT FROM AUTHOR]

Pathogenic variants of BRCA1/2 constitute hereditary breast and ovarian cancer (HBOC) syndrome, and BRCA1/2 mutant is a risk for various cancers. Whereas the clinical guideline for HBOC patients has been organized for the therapy and prevention of cancer, there is no recommendation on the female reproductive discipline. Indeed, the role of BRCA1/2 pathogenic variants in ovarian reserve has not been established due to the deficiency of appropriate animal models. Here, we used a rat model of Brca2(p.T1942fs/+) mutant of Sprague-Dawley strain with CRISPR-Cas9 editing to evaluate ovarian reserve in females. Fertility and ovarian follicles were evaluated and anti-Müllerian hormone (AMH) was measured at 8–32 weeks of age with a comparison between the wild-type and the mutant rats (MUT). MUT revealed a significantly smaller number of deliveries with fewer total pups. Furthermore, MUT showed a significant decrease in primordial follicles at 20 weeks and a low AMH level at 28 weeks. RNA-sequencing of the ovary at 10 weeks detected acceleration of the DNA damage repair pathway, which was accompanied by oxidative stress-induced DNA double-strand breaks, a decrease in PTEN, and an increase in mTOR in follicular granulosa cells. In conclusion, Brca2(p.T1942fs/+) dissipates primordial follicles via early activation of granulosa cells through oxidative stress, leading to earlier termination of fertility. [ABSTRACT FROM AUTHOR]

Background and Aim: Optimal tumor samples are crucial for successful analysis using commercially available comprehensive genomic profiling (CACGP). However, samples acquired by endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) are occasionally insufficient, and no consensus on the optimal number of needle passes required for CACGP exists. This study aimed to explore the optimal number of needle passes required for EUS‐TA to procure an ideal sample fulfilling the prerequisite criteria of CACGPs. Methods: Patients who underwent EUS‐TA for solid masses between November 2019 and July 2021 were retrospectively studied. The correlation between the acquisition rate of an ideal sample and the number of needle passes mounted on a microscope slide was evaluated. Additionally, the factors predicting a successful analysis were investigated in patients scheduled for CACGP using EUS‐TA‐obtained samples during the same period. Results: EUS‐TAs using 22‐ and 19‐gauge (G) needles were performed in 336 and 57 patients, respectively. There was a positive correlation between the acquisition rate and the number of passes using a 22‐G needle (38.9%, 45.0%, 83.7%, and 100% for 1, 2, 3, and 4 passes, respectively), while no correlation was found with a 19‐G needle (84.2%, 83.3%, and 85.0% for 1, 2, and 3 passes, respectively). The analysis success rate in patients with scheduled CACGP was significantly higher with ideal samples than with suboptimal samples (94.1% vs 55.0%, P < 0.01). Conclusions: The optimal estimated number of needle passes was 4 and 1–2 for 22‐ and 19‐G needles, respectively. [ABSTRACT FROM AUTHOR]