Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.

OBJECTIVE: Large (≥20 mm) sessile serrated lesions (L-SSL) are premalignant lesions that require endoscopic removal. Endoscopic mucosal resection (EMR) is the existing standard of care but carries some risk of adverse events including clinically significant post-EMR bleeding and deep mural injury (DMI). The respective risk-effectiveness ratio of piecemeal cold snare polypectomy (p-CSP) in L-SSL management is not fully known. DESIGN: Consecutive patients referred for L-SSL management were treated by p-CSP from April 2016 to January 2020 or by conventional EMR in the preceding period between July 2008 and March 2016 at four Australian tertiary centres. Surveillance colonoscopies were conducted at 6 months (SC1) and 18 months (SC2). Outcomes on technical success, adverse events and recurrence were documented prospectively and then compared retrospectively between the subsequent time periods. RESULTS: A total of 562 L-SSL in 474 patients were evaluated of which 156 L-SSL in 121 patients were treated by p-CSP and 406 L-SSL in 353 patients by EMR. Technical success was equal in both periods (100.0% (n=156) vs 99.0% (n=402)). No adverse events occurred in p-CSP, whereas delayed bleeding and DMI were encountered in 5.1% (n=18) and 3.4% (n=12) of L-SSL treated by EMR, respectively. Recurrence rates following p-CSP were similar to EMR at 4.3% (n=4) versus 4.6% (n=14) and 2.0% (n=1) versus 1.2% (n=3) for surveillance colonoscopy (SC)1 and SC2, respectively. CONCLUSIONS: In a historical comparison on the endoscopic management of L-SSL, p-CSP is technically equally efficacious to EMR but virtually eliminates the risk of delayed bleeding and perforation. p-CSP should therefore be considered as the new standard of care for L-SSL treatment.

Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?

OBJECTIVE: We evaluated the influence of the renin-angiotensin system (RAS) on intestinal inflammation and fibrosis. DESIGN: Cultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1-7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies. RESULTS: Human colonic myofibroblast proliferation was reduced by Ang (1-7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1-7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson's trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=-0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation. CONCLUSIONS: The RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.