Results of the COLDWATER randomized controlled trial: enhanced performance of underwater cold snare polypectomy for colorectal polyps 5-10 mm, independent of endoscopist experience.

Background: The wide range of R0 resection rates (R0RR) and incomplete resection rates (IRR) observed with conventional cold snare polypectomy (CCSP) emphasizes the necessity for technique enhancement. The COLDWATER study aimed to compare underwater cold snare polypectomy (UCSP) to CCSP for 5-10-mm colorectal polyps, focusing on comprehensive histopathological evaluation, efficacy, and safety. Methods: This was a randomized, single-blind, controlled trial comparing UCSP to CCSP for non-pedunculated colorectal polyps of size 5-10 mm. The primary outcome was to report differences in the muscularis mucosa resection ratio. The secondary outcomes focused on differences in depth of excision, R0-RR, IRR, en bloc resection rate, adverse events, and recurrence rate. Results: The COLDWATER study found higher muscularis mucosa resection in UCSP (81.72±62.81% vs. CCSP: 72.33±22.33%, P=0.003) with comparable submucosa presence (UCSP: 16.6%, CCSP: 12.5%, P=0.25). UCSP showed better outcomes regarding IRR (3.5% vs. 8.5%, P=0.05) and en bloc resection (98% vs. 93.5%, P=0.04). In CCSP, expert endoscopists achieved higher R0RR than non-experts, while UCSP showed no significant difference in R0RR across endoscopist's experience levels. Conclusions: UCSP achieves a more extensive excision of the muscularis mucosa compared to CCSP, even though it does not attain a deeper excision. Additionally, UCSP shows a higher en bloc resection rate, with lower rates of IRR, and emerges as a promising technique for training inexperienced endoscopists in polypectomy, given its experience-independent success in achieving R0 resection.

The Role of Hippo Signaling Pathway and ILK in the Pathophysiology of Human Hypertrophic Scars and Keloids: An Immunohistochemical Investigation.

BACKGROUND: Keloids and hypertrophic scars are characterized by abnormal fibroblast activation and proliferation. While their molecular pathogenesis remains unclear, myofibroblasts have been associated with their development. Hippo pathway effectors YAP/TAZ promote cell proliferation and matrix stiffening. Integrin-linked kinase (ILK), a central component of focal adhesions that mediates cell-matrix interactions, has been linked to tissue repair and fibrosis. The aim of this study was to investigate the expression of key Hippo pathway molecules and ILK in hypertrophic scars and keloids. METHODS: YAP/TAZ, TEAD4, ILK and a-SMA expression were evaluated by immunohistochemistry in keloids (n = 55), hypertrophic scars (n = 38) and normal skin (n = 14). RESULTS: The expression of YAP/TAZ, TEAD4, ILK and a-SMA was higher in fibroblasts of keloids compared to hypertrophic scars while negative in normal skin. There was a significant positive correlation between the expression of ILK and Hippo pathway effectors. CONCLUSIONS: Our results suggest that the deregulation of Hippo signaling and ILK are implicated in keloid and hypertrophic scar formation.

Investigation of prognostic biomarkers in patients with urothelial carcinoma treated with platinum-based regimens.

BACKGROUND: Bladder cancer (BC) is a heterogeneous malignancy with dismal outcome. PATIENTS AND METHODS: Mutations in genes, altered or linked to platinum sensitivity in BC, were examined in 66 patients' tumors along with tumor infiltrating lymphocytes (TILs) density and MMR, PD-L1 and CD8 protein expression, as well as basal and luminal subtypes, defined by protein expression of markers, including CK5/6 and GATA3 or CK20, respectively. RESULTS: 41 tumors harbored mutations, mainly in TP53 (38%), ARID1A (17%) and the DNA damage response and repair (DDR) genes ERCC2 (17%) and BRCA2 (15%). Mutations in other DDR relevant genes were also present. Age showed unfavorable prognosis for overall survival (HR=1.07, P = 0.026); no benefit was seen for patients with TP53, ARID1A, ERCC2 or BRCA2 mutations or mutations in 1 or more DDR genes. PD-L1 status positively correlated with stromal (rho=0.46, P < 0.001) and intratumoral (rho=0.53, P < 0.001) CD8 expression or TILs (rho=0.29, P = 0.018); none associated with overall survival (OS). A statistically significant difference was observed between PD-L1 status and immunohistochemistry (IHC)­based subtypes, with tumors classified as luminal (GATA3+ and/or CK20+ and CK5/6-) showing lower PD-L1 expression relative to basal (CK5/6+ and GATA3- and/or CK20-) (median value 0 vs. 2.5, P = 0.029). Concerning OS, no statistically significant difference was seen among patients with basal or luminal tumors. CONCLUSION: No association was seen herein between DDR mutations, TILs, PD-L1, CD8 expression or IHC-based subtypes and patient survival; these observations warrant validation within a larger cohort.