Citations

Abstract Introduction Underwater endoscopic mucosal resection (uEMR) technique has gained popularity for removal of large non-pedunculated colorectal polyps (LNPCPs) due to high en-bloc resection rates and lower recurrence rates. However, there is no information regarding outcomes of uEMR for giant colorectal polyps. Therefore, we aimed to evaluate the outcomes of uEMR for giant colorectal polyps across multiple centers in North America. Methods We conducted a multicenter retrospective study of adults with giant colorectal polyps undergoing uEMR between January 2019 and November 2025. Giant colorectal polyps were defined as LNPCPs ≥40 mm. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were severe adverse events (SAEs) and predictors of technical success, recurrence, and SAEs. Results A total of 137 polyps, with mean polyp size 47.6 mm were included. Majority of the lesions were located in right colon (61%, n = 83) with the most common histopathology being high-grade dysplasia (HGD) (31.4%, n = 43). Technical success was achieved in 90.5% (n = 124) with en-bloc resection rate of 11.7% (n = 16). Polyp fibrosis (OR: 0.08) and HGD (OR: 0.15) were independent predictors of inability to achieve technical success. Of 92 (67.1%) patients with follow-up, recurrent polyp was present in 8.7% (n = 8). SAEs were noted in 9.5%, consisting of delayed bleeding (9.5%, n = 13), while no delayed perforation or post polypectomy syndrome was noted. Discussion Our study demonstrates that uEMR is technically feasible for the removal of giant colorectal polyps with an acceptable safety profile and recurrence rate.

Abstract ZC3H18 is a multifunctional regulator of gene expression that is lost in a subset of high-grade serous ovarian cancers (HGSOC). Our prior studies have established that the loss of ZC3H18 diminishes BRCA1 levels, leading to the disruption of homologous recombination DNA repair (HR) and heightened sensitivity of HGSOC cells to PARP inhibitors. Here we show an additional facet to ZC3H18's impact, showing that its loss also induces a reprogramming of energy metabolism in HGSOC. Our findings demonstrate that the depletion of ZC3H18 results in reduced mRNA and protein levels of the NAD+-biosynthetic enzyme, NMNAT1, in HGSOC cells. Mechanistic studies uncovered that ZC3H18 occupies the NMNAT1 promoter, facilitating NMNAT1 transcription by recruiting CDK12 onto the promoter. Consistent with this mechanism, loss of ZC3H18 led to a reduction in CDK12 levels on the NMNAT1 promoter, diminishing NMNAT1 abundance and subsequently causing a decline in cellular NAD levels. These observations unveil a previously unknown role for ZC3H18 in HGSOC, shedding light on its involvement in the regulation of energy metabolism. Importantly, our findings provide valuable insights into potential therapeutic pathways that leverage the metabolic changes linked to ZC3H18 deficiency. Citation Format: Benjamin Wilson, Natalie Wilson, Xianfeng Chen, Shuwen Zhang, Chen Wang, Larry M. Karnitz, Scott H. Kaufmann, Arun Kanakkanthara. ZC3H18: A novel regulator of NAD+ metabolism in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4447.

Background Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR. Methods We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. I2 statistics were used to evaluate heterogeneity. Results 4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %–17.4 %, I2 = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %–35.7 %, I2 = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %–46.7 %, I2 = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %–9.9 %, I2 = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %–4.5 %, I2 = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %–2.7 %, I2 = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %–1.3 %, I2 = 0 %) and 0.6 % (95 %CI 0.3 %–1.4 %, I2 = 0 %), respectively. Conclusion CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.