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Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both. LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454. Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was −2·06 (95% CI −2·43 to −1·69; p<0·0001) in SINUS-24 and −1·80 (−2·10 to −1·51; p<0·0001) in SINUS-52; difference in nasal congestion or obstruction score was −0·89 (−1·07 to −0·71; p<0·0001) in SINUS-24 and −0·87 (−1·03 to −0·71; p<0·0001) in SINUS-52; and difference in Lund-Mackay CT scores was −7·44 (−8·35 to −6·53; p<0·0001) in SINUS-24 and −5·13 (−5·80 to −4·46; p<0·0001) in SINUS-52. The most common adverse events (nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema) were more frequent with placebo. In adult patients with severe CRSwNP, dupilumab reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. These results support the benefits of adding dupilumab to daily standard of care for patients with severe CRSwNP who otherwise have few therapeutic options. Sanofi and Regeneron Pharmaceuticals.

In patients with chronic severe rhinosinusitis and nasal polyps, tezepelumab therapy led to greater reductions in polyp size and nasal congestion and less use of surgery and glucocorticoids than placebo.

ObjectiveTo investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4–9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP).DesignA prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4–9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps.ResultsA total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI −1.0 to 2.7) complete resection rate (non-inferiority p<0.0001). Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group (0.5%, 2 of 402 polyps).ConclusionsThe complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4–9 mm colorectal polyps. (Study registration: UMIN000018328)

In this randomized trial involving 84,585 participants in Poland, Norway, and Sweden, the risk of colorectal cancer at 10 years was lower among those invited to undergo screening colonoscopy than among those assigned to no screening.

INTRODUCTION:Piecemeal polypectomy refers to the removal of large sessile colonic polyps by means of multiple snarings and is commonly performed after submucosal injection of a liquid, typically normal saline. Some reports suggest submucosal injection may not be benign, due to concerns of needle tracking of neoplastic cells, and difficulty in removal of recurrences due to scarring after injection. There is a paucity of recent literature describing polypectomy without submucosal injection. Historically, non-elevated piecemeal polypectomy has been criticized for concerns regarding bleeding and perforation. The purpose of this study was to describe a retrospective review of colonic polyps removed using non-elevated piecemeal polypectomy and associated outcomes.METHODS:An outpatient endoscopy center database was searched for patients who had large (≥3.0) sessile polyps excised using non-elevated piecemeal polypectomy technique between December 2012 and December 2018. All polyps with invasive cancer were excluded (n = 3). Chart review was carried out to extract demographic data, outcomes and adverse events. Details of all subsequent colonoscopies, including recurrences, residual tissue, or need for surgery were recorded.RESULTS:During the study period, 73 patients underwent 78 non-elevated piecemeal polypectomies for polyps ≥3 cm. There were 27 (37%) female patients and 46 (63%) male patients. Most common polyp sizes were between 3.5 cm to 3.9 cm (48.7%) or ≥4 cm (52.6%). Tubulovillous adenoma was the most frequent histological subtype (48.7%). Most polypectomies occurred in the right colon (54.4%). There were zero events of perforation. Ten (12.6%) patients had intraprocedural bleeding controlled endoscopically. Four patients (5.1%) had post-procedural bleeding, 3 required colonoscopy and clip hemostasis. There were 10 recurrences (12.8%), nine were found at the first endoscopic follow up and controlled by means of non-elevated hot snare polypectomy. One patient had a persistent recurrence and required subsequent surgical management for an adenocarcinoma.CONCLUSION:Non-elevated piecemeal polypectomy with hot snare is a safe and effective technique for the removal of large sessile (≥3 cm) colonic polyps. Perforation and bleeding are uncommon. Recurrences are easily controlled by additional hot snare resection.

INTRODUCTION:Colorectal polyps are an unusual cause of hematochezia and usually result from overlying ulcerations on adenomas or cancers. Non-adenomatous polyps, such as inflammatory polyps, may be a rare cause of gastrointestinal bleeding. Here, we present a case of a patient with painless hematochezia found to be originating from a bleeding anorectal inflammatory myoglandular polyp related to rectal prolapse.CASE DESCRIPTION/METHODS:A 51-year-old man with alcohol abuse and hepatitis C presented with fatigue and light-headedness along with 7-8 years of small volume painless hematochezia with bowel movements. He endorsed straining with bowel movements and something protruding from his anus that he would push back in. On physical exam, he was hemodynamically stable with a normal abdominal exam and a rectal exam revealing a palpable rectal mass without overt signs of bleeding. His lab work was notable for a hemoglobin of 5.5 g/dL. Magnetic resonance imaging (MRI) of the pelvis revealed rectal wall thickening and an enhancing mass abutting the anal sphincter (Figure 1). Colonoscopy revealed left-sided diverticulosis without bleeding and an ulcerated, vascular mass in the anal canal, best seen on retroflexion (Figures 2 and 3). Biopsies of the mass were consistent with an inflammatory myoglandular polyp thought to result from intermittent rectal prolapse. The mass was resected via transanal excision with complete resolution of hematochezia.DISCUSSION:Inflammatory myoglandular polyps are rare, non-neoplastic pedunculated polyps that are predominantly incidental findings during enemas or endoscopy but can present with hematochezia. While concentrated mostly in the distal colon, they can be seen in the descending and transverse colon as well. The etiology remains unknown, but there may be an association with mucosal prolapse and sigmoid diverticulosis. Specifically, it is hypothesized that chronic trauma from intestinal peristalsis may distort colonic crypt architecture, which results in muscularization of the lamina propria. This leads to subsequent redundancy and passive venous congestion that contributes to prolapse of these lesions. Generally, symptomatic inflammatory myoglandular polyps require endoscopic or surgical resection, which is curative. In this case, given the patient's symptoms along with the size and location, surgical management was indicated.