Feasibility and safety of endoscopic submucosal dissection for lesions in proximity to a colonic diverticulum

Background/Aims: Endoscopic submucosal dissection (ESD) for diverticulum-associated colorectal lesions is generally contraindicated because of the high risk of perforation. Several studies on patients with such lesions treated with ESD have been reported recently. However, the feasibility and safety of ESD for lesions in proximity to a colonic diverticulum (D-ESD) have not been fully clarified. The aim of this study was to evaluate the feasibility and safety of D-ESD. Methods: D-ESD was defined as ESD for lesions within approximately 3 mm of a diverticulum. Twenty-six consecutive patients who underwent D-ESD were included. Two strategic approaches were used depending on whether submucosal dissection of the diverticulum-related part was required (strategy B) or not (strategy A). Treatment outcomes and adverse events associated with each strategy were analyzed. Results: The en bloc resection rate was 96.2%. The R0 and curative resection rates were 76.4% and 70.6% in strategy A and 88.9% and 77.8% in strategy B, respectively. Two cases of intraoperative perforation and one case of delayed perforation occurred. The delayed perforation case required emergency surgery, but the other cases were managed conservatively. Conclusions: D-ESD may be a feasible treatment option. However, it should be performed in a high-volume center by expert hands because it requires highly skilled endoscopic techniques

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Endoscopic submucosal dissection of colitis-related dysplasia

Background and study aims Endoscopic submucosal dissection (ESD) offers en bloc resection of lesions, allowing precise pathological assessment. Although possible in ulcerative colitis (UC) patients, the chronic inflammation may increase the procedural risks and reduce the complete resection rate. The aim of this study was to assess the feasibility of ESD for UC and to consider the factors contributing to its technical difficulty. Patients and methods Multicenter experiences of ESD for UC were retrospectively analyzed by reviewing endoscopic videos, pictures, reports, and clinical notes. Results A total of 32 dysplastic lesions were included (23 in British patients, 9 in Japanese patients). The lesions were macroscopically flat or with subtle extension macroscopically in 30 patients (94 %), with a median size of 33 mm (range 12 - 73 mm), and were located in the distal colon, including one on a pouch anastomosis. Submucosal fibrosis and adipose deposition were observed in 31 (97 %) and 13 lesions (41 %), respectively. En bloc resection was possible in 29/32 lesions (91 %). One patient had delayed bleeding. Advanced pathology was observed in 11 lesions (35 %). Recurrence was observed in only one patient (after a median of 33 months [range 6 - 76 months]); however, three patients developed metachronous lesions. Conclusions ESD is feasible for UC dysplasia without an increased rate of complications. Submucosal fibrosis and fat deposition were frequently observed and contributed to the technical complexity. Careful and intensive follow-up should be organized to detect metachronous lesions

Endoscopic submucosal dissection of colitis-related dysplasia

Background and study aims Endoscopic submucosal dissection (ESD) offers en bloc resection of lesions, allowing precise pathological assessment. Although possible in ulcerative colitis (UC) patients, the chronic inflammation may increase the procedural risks and reduce the complete resection rate. The aim of this study was to assess the feasibility of ESD for UC and to consider the factors contributing to its technical difficulty. Patients and methods Multicenter experiences of ESD for UC were retrospectively analyzed by reviewing endoscopic videos, pictures, reports, and clinical notes. Results A total of 32 dysplastic lesions were included (23 in British patients, 9 in Japanese patients). The lesions were macroscopically flat or with subtle extension macroscopically in 30 patients (94 %), with a median size of 33 mm (range 12 - 73 mm), and were located in the distal colon, including one on a pouch anastomosis. Submucosal fibrosis and adipose deposition were observed in 31 (97 %) and 13 lesions (41 %), respectively. En bloc resection was possible in 29/32 lesions (91 %). One patient had delayed bleeding. Advanced pathology was observed in 11 lesions (35 %). Recurrence was observed in only one patient (after a median of 33 months [range 6 - 76 months]); however, three patients developed metachronous lesions. Conclusions ESD is feasible for UC dysplasia without an increased rate of complications. Submucosal fibrosis and fat deposition were frequently observed and contributed to the technical complexity. Careful and intensive follow-up should be organized to detect metachronous lesions