Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death.

BACKGROUND: Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear. METHODS: We performed a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause. RESULTS: Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval [CI], 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04). CONCLUSIONS: In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.).

Rates of repeated colonoscopies to clean the colon from low-risk and high-risk adenomas: results from the EPoS trials.

OBJECTIVE: High-quality colonoscopy (adequate bowel preparation, whole-colon visualisation and removal of all neoplastic polyps) is a prerequisite to start polyp surveillance, and is ideally achieved in one colonoscopy. In a large multinational polyp surveillance trial, we aimed to investigate clinical practice variation in number of colonoscopies needed to enrol patients with low-risk and high-risk adenomas in polyp surveillance. DESIGN: We retrieved data of all patients with low-risk adenomas (one or two tubular adenomas <10 mm with low-grade dysplasia) and high-risk adenomas (3-10 adenomas, ≥1 adenoma ≥10 mm, high-grade dysplasia or villous components) in the European Polyp Surveillance trials fulfilling certain logistic and methodologic criteria. We analysed variations in number of colonoscopies needed to achieve high-quality colonoscopy and enter polyp surveillance by endoscopy centre, and by endoscopists who enrolled ≥30 patients. RESULTS: The study comprised 15 581 patients from 38 endoscopy centres in five European countries; 6794 patients had low-risk and 8787 had high-risk adenomas. 961 patients (6.2%, 95% CI 5.8% to 6.6%) underwent two or more colonoscopies before surveillance began; 101 (1.5%, 95% CI 1.2% to 1.8%) in the low-risk group and 860 (9.8%, 95% CI 9.2% to 10.4%) in the high-risk group. Main reasons were poor bowel preparation (21.3%) or incomplete colonoscopy/polypectomy (14.4%) or planned second procedure (27.8%). Need of repeat colonoscopy varied between study centres ranging from 0% to 11.8% in low-risk adenoma patients and from 0% to 63.9% in high-risk adenoma patients. On the second colonoscopy, the two most common reasons for a repeat (third) colonoscopy were piecemeal resection (26.5%) and unspecified reason (23.9%). CONCLUSION: There is considerable practice variation in the number of colonoscopies performed to achieve complete polyp removal, indicating need for targeted quality improvement to reduce patient burden. TRIAL REGISTRATION NUMBER: NCT02319928.

Comparison of Quality Measures for Detection of Neoplasia at Screening Colonoscopy.

BACKGROUND & AIMS: The proportion of colonoscopies with at least one adenoma (adenoma detection rate [ADR]) is inversely associated with colorectal cancer (CRC) risk and death. The aim of this study was to examine whether such associations exist for colonoscopy quality measures other than ADR. METHODS: We used data from the Polish Colorectal Cancer Screening Program collected in 2000-2011. For all endoscopists who performed ≥100 colonoscopies we calculated detection rates of adenomas (ADR), polyps (PDR), and advanced adenomas (≥10 mm/villous component/high-grade dysplasia [AADR]); and number of adenomas per colonoscopy (APC) and per colonoscopy with ≥1 adenoma (APPC). We followed patients until CRC diagnosed before recommended surveillance, death, or December 31, 2019. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional-hazard models. We used Harrell's C statistic to compare the predictive power of the quality measures. RESULTS: Data on 173,287 patients (median age, 56 years; 37.8% male) and 262 endoscopists were used. During a median follow-up of 10 years and 1,490,683 person-years, we identified 395 CRCs. All quality measures were significantly associated with CRC risk and death. The relative reductions in CRC risk were as follows: for ADR ≥24.9% (reference <12.1%; HR, 0.41; 95% CI, 0.25-0.66), PDR ≥42.7% (reference <19.9%; HR, 0.35; 95% CI, 0.24-0.51), AADR ≥9.1% (reference <4.1%; HR, 0.69; 95% CI, 0.49-0.96), APC ≥0.37 (reference <0.15; HR, 0.35; 95% CI, 0.21-0.58), and APPC ≥1.54 (reference <1.19; HR, 0.54; 95% CI, 0.35-0.83). AADR was the only quality measure with significantly lower predictive power than ADR (Harrell's C, 59.7 vs 63.4; P = .001). Similar relative reductions were observed for CRC death. CONCLUSIONS: This large observational study confirmed the inverse association between ADR and CRC risk and death. The PDR and APC quality measures appear to be comparable with ADR.

HPV testing in Polish population-based cervical cancer screening programme (HIPPO project)-study protocol of a randomised healthcare policy trial.

BACKGROUND: An Organised Cervical Cancer Screening Programme (OCCSP) was started in Poland in 2006/2007. Each woman aged 25 to 59 is eligible for a free Pap test every 3 years in OCCSP. Despite implementation of the OCCSP, the age-standardised cervical cancer (CC) incidence and mortality rates in 2019 were 7.3/100 000 and 3.9/100 000 respectively and were still higher than those in Western European countries with well-organised screening programmes. Apart from low coverage of the OCCSP, suboptimal performance of the screening test (conventional cytology) may be partially responsible for this situation. Several countries have already incorporated high risk Human Papillomavirus (hrHPV) testing in CC screening as a more sensitive tool reducing the risk of missing precancerous lesions and allowing for extension of screening intervals. The European Guidelines for Quality Assurance in Cervical Cancer Screening recommend pilot evaluation of a new screening test in country-specific conditions before its implementation. METHODS: The HIPPO project (HPV testing In Polish POpulation-based cervical cancer screening program) is a randomised health services study nested in the OCCSP in Poland. The project will randomise 33 000 women aged 30-59 years to cytology or hrHPV testing (ratio: 1:1) with age stratification. In the cytology arm women with repeated Atypical Squamous Cells of Undetermined Significance (ASC-US) or ≥ Low-Grade Squamous Intraepithelial Lesions (LSIL) are referred for colposcopy. In the other arm, hrHPV ( +) women with ≥ ASC-US reflex Liquid-Based Cytology (LBC) are referred for colposcopy. Primary endpoints include detection rates of histologically confirmed high grade intraepithelial lesions or worse (CIN2 +) in each arm. DISCUSSION: This pilot randomised healthcare study nested in the OCCSP in Poland will assess and compare the performance of hrHPV testing to current standard-cytology in order to make decisions on implementation of HPV-based screening in the country. TRIAL REGISTRATION: This randomised healthcare service study was prospectively registered at https://clinicaltrials.gov/ (identifier: NCT04111835, protocol ID 28/2019) on 19th of September 2019.

Speedometer for withdrawal time monitoring during colonoscopy: a clinical implementation trial.

OBJECTIVES: Meticulous inspection of the mucosa during colonoscopy, represents a lengthier withdrawal time, but has been shown to increase adenoma detection rate (ADR). We investigated if artificial intelligence-aided speed monitoring can improve suboptimal withdrawal time. METHODS: We evaluated the implementation of a computer-aided speed monitoring device during colonoscopy at a large academic endoscopy center. After informed consent, patients ≥18 years undergoing colonoscopy between 5 March and 29 April 2021 were examined without the use of the speedometer, and with the speedometer between 29 April and 30 June 2021. All colonoscopies were recorded, and withdrawal time was assessed based on the recordings in a blinded fashion. We compared mean withdrawal time, percentage of withdrawal time ≥6 min, and ADR with and without the speedometer. RESULTS: One hundred sixty-six patients in each group were eligible for analyses. Mean withdrawal time was 9 min and 6.6 s (95% CI: 8 min and 34.8 s to 9 min and 39 s) without the use of the speedometer, and 9 min and 9 s (95% CI: 8 min and 45 s to 9 min and 33.6 s) with the speedometer; difference 2.3 s (95% CI: -42.3-37.7, p = 0.91). The ADRs were 45.2% (95% CI: 37.6-52.8) without the speedometer as compared to 45.8% (95% CI: 38.2-53.4) with the speedometer (p = 0.91). The proportion of colonoscopies with withdrawal time ≥6 min without the speedometer was 85.5% (95% CI: 80.2-90.9) versus 86.7% (95% CI: 81.6-91.9) with the speedometer (p = 0.75). CONCLUSIONS: Use of speed monitoring during withdrawal did not increase withdrawal time or ADR in colonoscopy. CLINICALTRIALS.GOV IDENTIFIER: NCT04710251.

Participation in Competing Strategies for Colorectal Cancer Screening: A Randomized Health Services Study (PICCOLINO Study).

BACKGROUND & AIMS: Primary colonoscopy and fecal immunochemical testing (FIT) are considered first-tier tests for colorectal cancer (CRC) screening. Although colonoscopy is considered the most efficacious test, FIT might achieve higher participation rates. It is uncertain what the best strategy is for offering population-wide CRC screening. METHODS: This was a multicenter randomized health services study performed within the framework of the Polish Colonoscopy Screening Program between January 2019 and March 2020 on screening-naïve individuals. Eligible candidates were randomly assigned in a 1:1:1 ratio to participate in 1 of 3 competing invitation strategies: control (invitation to screening colonoscopy only); sequential (invitation to primary colonoscopy and invitation for FIT for initial nonresponders); or choice (invitation offering a choice of colonoscopy or FIT). The primary outcome was participation in CRC screening within 18 weeks after enrollment into the study. The secondary outcome was diagnostic yield for advanced neoplasia. RESULTS: Overall, 12,485 individuals were randomized into the 3 study groups. The participation rate in the control group (17.5%) was significantly lower compared with the sequential (25.8%) and choice strategy (26.5%) groups (P < .001 for both comparisons). The colonoscopy rates for participants with positive FITs were 70.0% for the sequential group and 73.3% for the choice group, despite active call-recall efforts. In the intention-to-screen analysis, advanced neoplasia detection rates were comparable among the control (1.1%), sequential (1.0%), and choice groups (1.1%). CONCLUSIONS: Offering a combination of FIT and colonoscopy as a sequential or active choice strategy increases participation in CRC screening. Increased participation in strategies with FIT do not translate into higher detection of advanced neoplasia. ClinicalTrials.gov, Number NCT03790475.

Colonoscopist Performance and Colorectal Cancer Risk After Adenoma Removal to Stratify Surveillance: Two Nationwide Observational Studies.

BACKGROUND AND AIMS: Colonoscopy surveillance after adenoma removal is an increasing burden in many countries. Surveillance recommendations consider characteristics of removed adenomas, but not colonoscopist performance. We investigated the impact of colonoscopist performance on colorectal cancer risk after adenoma removal. METHODS: We compared colorectal cancer risk after removal of high-risk adenomas, low-risk adenomas, and after negative colonoscopy for all colonoscopies performed by colonoscopists with low vs high performance quality (adenoma detection rate <20% vs ≥20%) in the Polish screening program between 2000 and 2011, with follow-up until 2017. Findings were validated in the Austrian colonoscopy screening program. RESULTS: A total of 173,288 Polish colonoscopies were included in the study. Of 262 colonoscopists, 160 (61.1%) were low performers, and 102 (38.9%) were high performers; 11.1% of individuals had low-risk and 6.6% had high-risk adenomas removed at screening; 82.2% had no adenomas. During 10 years of follow-up, 443 colorectal cancers were diagnosed. For low-risk adenoma individuals, colorectal cancer incidence was 0.55% (95% confidence interval [CI] 0.40-0.75) with low-performing colonoscopists vs 0.22% (95% CI 0.14-0.34) with high-performing colonoscopists (hazard ratio [HR] 2.35; 95% CI 1.31-4.21; P = .004). For individuals with high-risk adenomas, colorectal cancer incidence was 1.14% (95% CI 0.87-1.48) with low-performing colonoscopists vs 0.43% (95% CI 0.27-0.69) with high-performing colonoscopists (HR 2.69; 95% CI 1.62-4.47; P < .001). After negative colonoscopy, colorectal cancer incidence was 0.30% (95% CI 0.27-0.34) for individuals examined by low-performing colonoscopists, vs 0.15% (95% CI 0.11-0.20) for high-performing (HR 2.10; 95% CI 1.52-2.91; P < .001). The observed trends were reproduced in the Austrian validation cohort. CONCLUSIONS: Our results suggest that endoscopist performance may be an important contributor in addition to polyp characteristics in determining colorectal cancer risk after colonoscopy screening.

Prevalence and risk factors of upper gastrointestinal cancers missed during endoscopy: a nationwide registry-based study.

BACKGROUND: A significant proportion of upper gastrointestinal cancers (UGICs) remain undetected during esophagogastroduodenoscopy (EGD). We investigated the characteristics and risk factors of UGICs missed during endoscopy. METHODS: In this nationwide registry-based study, we analyzed two large Polish datasets (National Health Fund and National Cancer Registry) to identify individuals who underwent EGD and were subsequently diagnosed with UGIC. Cancers diagnosed < 6 months after EGD were defined as "prevalent" and those within ≥ 6- < 36 months as "missed." We compared the characteristics of missed and prevalent cancers, and analyzed the risk factors for missed UGICs in a multivariable regression model. RESULTS: We included 4 105 399 patients (mean age 56.0 years [SD 17.4]; 57.5 % female) who underwent 5 877 674 EGDs in 2012-2018. Within this cohort, 33 241 UGICs were diagnosed, of which 1993 (6.0 %) were missed. Within esophageal neoplasms, adenocarcinomas were more frequently missed than squamous cell cancers (6.1 % vs. 4.2 %), with a relative risk of 1.4 (95 % confidence interval [CI] 1.1-1.8, P = 0.01). Most gastric cancers were adenocarcinomas, of which 5.7 % were classified as missed. Overall, a higher proportion of missed UGICs than prevalent cancers presented at an advanced stage (42.2 % vs. 36.2 %, P < 0.001). Risk factors for missed UGICs included initial EGD performed within primary (vs. secondary) care (odds ratio [OR] 1.3, 95 %CI 1.2-1.5), female sex (OR 1.3, 95 %CI 1.2-1.4), and higher comorbidity (Charlson comorbidity index ≥ 5 vs. 0; OR 6.0, 95 %CI 4.7-7.5). CONCLUSIONS: Among UGICs, esophageal adenocarcinomas were missed most frequently. Missed cancers occur more frequently within the primary care sector and are found more often in women and individuals with multiple comorbidities.

A novel intragastric balloon for treatment of obesity and type 2 diabetes. A two-center pilot trial.

BACKGROUND AND AIMS: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. PATIENTS AND METHODS: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. RESULTS: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. CONCLUSIONS: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

Long-term observation of gastric patients with positive immunocytochemistry of peritoneal washing.

Prognosis in gastric cancer patients is highly dependent on the tumor stage at presentation. Surgery still remains the main therapeutic option in gastric cancer patients. However, the efficacy of this treatment may be substantially limited by the risk of peritoneal dissemination. The introduction of hyperthermic intraperitoneal chemotherapy (HIPEC) may affect the long-term outcomes in this group of patients, but high morbidity associated with this procedure provides the rationale to identify the correct population of patients for HIPEC. The aim of the study was to evaluate a long-term prognostic value of peritoneal washing immunocytochemistry as a prognostic factor in patients with gastric cancer. This is a prospective, long-term analysis of patients who underwent peritoneal lavage with immunocytochemistry assessment in the Maria Sklodowska-Curie National Research Institute of Oncology, in Warsaw, Poland. Between January 2002 and November 2004, a total of 157 patients with histologically confirmed gastric cancer were enrolled in the study. Laparotomy and intra-operative peritoneal lavage for immunocytochemistry examination were performed prior to gastrectomy. All patients were followed up with endpoints of cancer recurrence and mortality. Positive peritoneal washing immunocytochemistry was associated with clinical staging of gastric cancer, overall survival, and progression-free survival. It is an independent poor outcome prognostic factor.

Safety and efficacy of the FLOT regimen in the Polish population - an analysis of the prospective trial.

As gastric cancer is associated with poor prognosis, the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in European patients is perioperative chemotherapy using the FLOT regimen. Previously published data demonstrate that such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. In order to collect biomaterial for the identification of serum biomarkers of an early response to neoadjuvant chemotherapy, we performed a prospective study and here, we report the safety and clinical efficacy of this prospective cohort. It was an academic, nonrandomized, prospective study, conducted at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Between January 2018 and November 2019, we analyzed a total of 61 patients aged 30-77 (median 63 years, 52.5% males and 47.5% females) with histologically confirmed GC or GEJ cancer. The patients were qualified by a multidisciplinary team for perioperative treatment (FLOT regimen). All cases of reported adverse events were recorded and analyzed. All patients received G-CSF prophylactically. After gastrectomy, an assessment of pathological regression was performed according to the Becker classification. A total of 93.4% (57) patients completed four cycles of preoperative chemotherapy and 78.7% (48) received postoperative chemotherapy. All of them experienced grade 1/2 toxicities. The common AE G1/G2 in preoperative versus postoperative chemotherapy were: fatigue (75% vs. 60%), anemia (64% vs. 62%), nausea (60% vs. 60%), peripheral neuropathy (60% vs. 60%), and oral mucositis (59% vs. 50%), respectively. Only 24.6% (15) had G3/4 adverse events during preoperative chemotherapy and only 20.8% (10) during postoperative chemotherapy. The estimated DFS at 3 years was 53% (95% CI 40.5-66.1%) and the estimated OS at 3 years was 60.2% (95% CI 45.1-72.3%). FLOT regimen significantly improved GC and GEJ cancer patients' prognosis with acceptable side-effect profiles.

Colorectal Cancer Incidence and Mortality After Removal of Adenomas During Screening Colonoscopies.

BACKGROUND & AIMS: Recommendation of surveillance colonoscopy should be based on risk of colorectal cancer and death after adenoma removal. We aimed to develop a risk classification system based on colorectal cancer incidence and mortality following adenoma removal. METHODS: We performed a multicenter population-based cohort study of 236,089 individuals (median patient age, 56 years; 37.8% male) undergoing screening colonoscopies with adequate bowel cleansing and cecum intubation at 132 centers in the Polish National Colorectal Cancer Screening Program, from 2000 through 2011. Subjects were followed for a median 7.1 years and information was collected on colorectal cancer development and death. We used recursive partitioning and multivariable Cox models to identify associations between colorectal cancer risk and patient and adenoma characteristics (diameter, growth pattern, grade of dysplasia, and number of adenomas). We developed a risk classification system based on standardized incidence ratios, using data from the Polish population for comparison. The primary endpoints were colorectal cancer incidence and colorectal cancer death. RESULTS: We identified 130 colorectal cancers in individuals who had adenomas removed at screening (46.5 per 100,000 person-years) vs 309 in individuals without adenomas (22.2 per 100,000 person-years). Compared with individuals without adenomas, adenomas ≥20 mm in diameter and high-grade dysplasia were associated with increased risk of colorectal cancer (adjusted hazard ratios 9.25; 95% confidence interval [CI] 6.39-13.39, and 3.58; 95% CI 1.96-6.54, respectively). Compared with the general population, colorectal cancer risk was higher or comparable only for individuals with adenomas ≥20 mm in diameter (standardized incidence ratio [SIR] 2.07; 95% CI 1.40-2.93) or with high-grade dysplasia (SIR 0.79; 95% CI 0.39-1.41), whereas for individuals with other adenoma characteristics the risk was lower (SIR 0.35; 95% CI 0.28-0.44). We developed a high-risk classification based on adenoma size ≥20 mm or high-grade dysplasia (instead of the current high-risk classification cutoff of ≥3 adenomas or any adenoma with villous growth pattern, high-grade dysplasia, or ≥10 mm in diameter). Our classification system would reduce the number of individuals classified as high-risk and requiring intensive surveillance from 15,242 (36.5%) to 3980 (9.5%), without increasing risk of colorectal cancer in patients with adenomas (risk difference per 100,000 person-years, 5.6; 95% CI -10.7 to 22.0). CONCLUSIONS: Using data from the Polish National Colorectal Cancer Screening Program, we developed a risk classification system that would reduce the number of individuals classified as high risk and require intensive surveillance more than 3-fold, without increasing risk of colorectal cancer in patients with adenomas. This system could optimize the use of surveillance colonoscopy.

Argon plasma coagulation for Barrett's esophagus with low-grade dysplasia: a randomized trial with long-term follow-up on the impact of power setting and proton pump inhibitor dose.

BACKGROUND: This study evaluated the impact of power setting and proton pump inhibitor (PPI) dose on efficacy and safety of argon plasma coagulation (APC) of Barrett's esophagus (BE) with low-grade dysplasia (LGD). METHODS : 71 patients were randomized to APC with power set at 90 W or 60 W followed by 120 mg or 40 mg omeprazole. The primary outcome was the rate of complete (endoscopic and histologic) ablation of BE at 6 weeks. Secondary outcomes included safety and long-term efficacy. RESULTS : Complete ablation rate in the 90 W/120 mg, 90 W/40 mg, and 60 W/120 mg groups was 78 % (18/23; 95 % confidence interval [CI] 61-95), 60 % (15/25; 95 %CI 41-79), 74 % (17/23; 95 %CI 56-92), respectively, at 6 weeks and 70 % (16/23; 95 %CI 51-88), 52 % (13/25; 95 %CI 32-72), and 65 % (15/23; 95 %CI 46-85) at 2 years post-treatment (differences not significant). Additional APC was required in 28 patients (23 residual and 5 recurrent BE). At median follow-up of 108 months, 66/71 patients (93 %; 95 %CI 87-99) maintained complete ablation. No high-grade dysplasia or adenocarcinoma developed. Overall, adverse events (97 % mild) did not differ significantly between groups. Chest pain/discomfort was more frequent in patients receiving 90 W vs. 60 W power (P < 0.001). One patient had esophageal perforation and two developed stenosis. CONCLUSIONS: APC power setting and PPI dose did not impact efficacy and safety of BE ablation. Complete ablation of BE with LGD was durable in > 90 % of patients, without any evidence of neoplasia progression in the long term.

Covid-19 transmission in fitness centers in Norway - a randomized trial.

BACKGROUND: Closed fitness centers during the Covid-19 pandemic may negatively impact health and wellbeing. We assessed whether training at fitness centers increases the risk of SARS-CoV-2 virus infection. METHODS: In a two-group parallel randomized controlled trial, fitness center members aged 18 to 64 without Covid-19-relevant comorbidities, were randomized to access to training at a fitness center or no-access. Fitness centers applied physical distancing (1 m for floor exercise, 2 m for high-intensity classes) and enhanced hand and surface hygiene. Primary outcomes were SARS-CoV-2 RNA status by polymerase chain reaction (PCR) after 14 days, hospital admission after 21 days. The secondary endpoint was SARS-CoV-2 antibody status after 1 month. RESULTS: 3764 individuals were randomized; 1896 to the training arm and 1868 to the no-training arm. In the training arm, 81.8% trained at least once, and 38.5% trained ≥six times. Of 3016 individuals who returned the SARS-CoV-2 RNA tests (80.5%), there was one positive test in the training arm, and none in the no-training arm (risk difference 0.053%; 95% CI - 0.050 to 0.156%; p = 0.32). Eleven individuals in the training arm (0.8% of tested) and 27 in the no-training arm (2.4% of tested) tested positive for SARS-CoV-2 antibodies (risk difference - 0.87%; 95%CI - 1.52% to - 0.23%; p = 0.001). No outpatient visits or hospital admissions due to Covid-19 occurred in either arm. CONCLUSION: Provided good hygiene and physical distancing measures and low population prevalence of SARS-CoV-2 infection, there was no increased infection risk of SARS-CoV-2 in fitness centers in Oslo, Norway for individuals without Covid-19-relevant comorbidities. TRIAL REGISTRATION: The trial was prospectively registered in ClinicalTrials.gov on May 13, 2020. Due to administrative issues it was first posted on the register website on May 29, 2020: NCT04406909 .

Intravoxel incoherent motion MRI in evaluating inflammatory activity in ulcerative colitis: a pilot study.

BACKGROUND: A non-invasive tool for the assessment of ulcerative colitis (UC) activity is needed for treatment control. PURPOSE: To determine the efficacy of intravoxel incoherent motion (IVIM) in assessing inflammatory activity in UC. MATERIAL AND METHODS: In this prospective study, 20 adult patients underwent 3.0-T magnetic resonance imaging (MRI) IVIM diffusion-weighted imaging (DWI) with 10 b-values (0-900 s/mm2) 0-6 days after biopsies entailing colonoscopy. The inflammatory activity of large bowel segments was graded on endoscopy with Mayo score and on pathology with a six­grade classification system. IVIM­derived parameters (f, D, and D*) calculated from regions of interest placed within the bowel wall were correlated with both scores (56 and 34 bowel segments, respectively). Radiologists were blinded to endoscopy and pathology results. A T-test and Wilcoxon rank sum test was used in comparisons and receiver operating characteristic curve analysis was performed. RESULTS: Statistically significant differences were found between histopathologically inactive or mild activity and moderate to severe activity in f (respectively: mean = 0.19 and mean = 0.28, P = 0.024; area under the curve [AUC] = 0.723, sensitivity 0.82, specificity 0.59, accuracy 0.67 for a 0.185 cut-off value) and D (mean = 1.34 × 10-3mm2/s and mean = 1.07 × 10-3mm2/s, P = 0.0083; AUC = 0.735, sensitivity 0.91, specificity 0.54, accuracy 0.66 for cut-off value 1.24 × 10-3mm2/s). No significant difference in D* was noted. No significant correlation between Mayo endoscopic subscore, and f, D, nor D* was found. CONCLUSION: IVIM perfusion fraction correlates with UC activity and might represent emerging tool in assessment of inflammatory activity.

Long-Term Colorectal Cancer Incidence and Mortality After a Single Negative Screening Colonoscopy.

BACKGROUND: Current guidelines recommend a 10-year interval between screening colonoscopies, but evidence is limited. OBJECTIVE: To assess the long-term risk for colorectal cancer (CRC) and death from CRC after a high- and low-quality single negative screening colonoscopy. DESIGN: Observational study. SETTING: Polish Colonoscopy Screening Program. PARTICIPANTS: Average-risk individuals aged 50 to 66 years who had a single negative colonoscopy (no neoplastic findings). MEASUREMENTS: Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) of CRC after high- and low-quality single negative screening colonoscopy. High-quality colonoscopy included a complete examination, with adequate bowel preparation, performed by endoscopists with an adenoma detection rate of 20% or greater. RESULTS: Among 165 887 individuals followed for up to 17.4 years, CRC incidence (0.28 [95% CI, 0.25 to 0.30]) and mortality (0.19 [CI, 0.16 to 0.21]) were 72% and 81% lower, respectively, than in the general population. High-quality examination resulted in 2-fold lower CRC incidence (SIR, 0.16 [CI, 0.13 to 0.20]) and mortality (SMR, 0.10 [CI, 0.06 to 0.14]) than low-quality examination (SIR, 0.32 [CI, 0.29 to 0.35]; SMR, 0.22 [CI, 0.18 to 0.25]). In multivariable analysis, the hazard ratios for CRC incidence after high-quality versus low-quality colonoscopy were 0.55 (CI, 0.35 to 0.86) for 0 to 5 years, 0.54 (CI, 0.38 to 0.77) for 5.1 to 10 years, and 0.46 (CI, 0.25 to 0.86) for 10 to 17.4 years. Only after high-quality colonoscopy did the SIR and SMR for 10.1 to 17.4 years of follow-up not differ compared with earlier observation periods. LIMITATION: The general population was used as the comparison group. CONCLUSION: A single negative screening colonoscopy was associated with reduced CRC incidence and mortality for up to 17.4 years. Only high-quality colonoscopy yielded profound and stable reductions in CRC incidence and mortality throughout the entire follow-up. PRIMARY FUNDING SOURCE: Polish Ministry of Health.

Mortality and Rate of Hospitalization in a Colonoscopy Screening Program From a Randomized Health Services Study.

BACKGROUND & AIMS: It is difficult to quantify adverse events related to screening colonoscopy due to lack of valid and adequately powered comparison groups. We compared mortality and rate of unplanned hospitalizations among subjects who underwent screening colonoscopies within the Polish Colonoscopy Screening Program (PCSP) vs unscreened matched controls in Poland. METHODS: Persons 55-64 years old living in the area covered by the PCSP from 2012 through 2015 were assigned in a (1:1) to a group invited for screening colonoscopy (n = 338,477) or a matched group that would be invited 5 years later (controls, n = 338,557). All subjects in the screening group were assigned proposed screening colonoscopy dates (actual dates when invitees confirmed or rescheduled colonoscopy) and those in the control group were assigned virtual dates corresponding to the matched individuals from the screening group. In the screening group, 55,390 subjects (16.4%) underwent screening colonoscopy. Mortality and hospitalization data were obtained from National Registries. We compared mortality and rate of hospitalization between the groups for defined intervals before and after colonoscopy date. Hospitalizations were divided into related and unrelated to colonoscopy based on ICD codes by 3 specialists. Our primary aim was to compare mortality and hospitalization 6 weeks before and 30 days following the actual or virtual date of colonoscopy in the screening or control group. RESULTS: In the intent to treat analysis, overall there were no significant differences in mortality between the colonoscopy group and control group (0.22% vs 0.22%; risk difference less than .01%; 95% CI, decrease of 0.02% to 0.02%; P = .913). The overall rate of unplanned hospitalization was significantly higher for the colonoscopy group (2.39% vs 2.31% for the control group; risk difference, 0.08%; 95% CI, 0.01%-0.15%; P=.026) for the entire observation period. This was due to the higher rate of hospitalizations after screening (1.10% vs 1.01% for the control group; risk difference, 0.09%; 95% CI, 0.04%-0.14%; P < .001) including higher proportion of hospitalizations that were assessed as related to colonoscopy (0.24% vs 0.22% for the control group; risk difference, 0.02%; 95% CI, 0.00%-0.05%; P = .046). In the per-protocol analysis, the overall rate of hospitalizations did not differ significantly between control and screening colonoscopy groups (1.87% vs 1.90%; P=.709). However, screening colonoscopy did increase rates of related hospitalizations after the date of screening (from 0.14% to 0.31%; P < .001). CONCLUSIONS: In an analysis of data from the PCSP, we found high-quality evidence that colonoscopy as a screening intervention does not increase mortality before or after colonoscopy. However, it may be associated with a small but significant increase in unplanned hospitalizations, especially after the colonoscopy is completed.

Diminutive Polyps With Advanced Histologic Features Do Not Increase Risk for Metachronous Advanced Colon Neoplasia.

BACKGROUND & AIMS: With advances in endoscopic imaging, it is possible to differentiate adenomatous from hyperplastic diminutive (1-5 mm) polyps during endoscopy. With the optical Resect-and-Discard strategy, these polyps are then removed and discarded without histopathology assessment. However, failure to recognize adenomas (vs hyperplastic polyps), or discarding a polyp with advanced histologic features, could result in a patient being considered at low risk for metachronous advanced neoplasia, resulting in an inappropriately long surveillance interval. We collected data from international cohorts of patients undergoing colonoscopy to determine what proportion of patients are high risk because of diminutive polyps advanced histologic features and their risk for metachronous advanced neoplasia. METHODS: We collected data from 12 cohorts (in the United States or Europe) of patients undergoing colonoscopy after a positive result from a fecal immunochemical test (FIT cohort, n = 34,221) or undergoing colonoscopies for screening, surveillance, or evaluation of symptoms (colonoscopy cohort, n = 30,123). Patients at high risk for metachronous advanced neoplasia were defined as patients with polyps that had advanced histologic features (cancer, high-grade dysplasia, ≥25% villous features), 3 or more diminutive or small (6-9 mm) nonadvanced adenomas, or an adenoma or sessile serrated lesion ≥10 mm. Using an inverse variance random effects model, we calculated the proportion of diminutive polyps with advanced histologic features; the proportion of patients classified as high risk because their diminutive polyps had advanced histologic features; and the risk of these patients for metachronous advanced neoplasia. RESULTS: In 51,510 diminutive polyps, advanced histologic features were observed in 7.1% of polyps from the FIT cohort and 1.5% polyps from the colonoscopy cohort (P = .044); however, this difference in prevalence did not produce a significant difference in the proportions of patients assigned to high-risk status (0.8% of patients in the FIT cohort and 0.4% of patients in the colonoscopy cohort) (P = .25). The proportions of high-risk patients because of diminutive polyps with advanced histologic features who were found to have metachronous advanced neoplasia (17.6%) did not differ significantly from the proportion of low-risk patients with metachronous advanced neoplasia (14.6%) (relative risk for high-risk categorization, 1.13; 95% confidence interval 0.79-1.61). CONCLUSION: In a pooled analysis of data from 12 international cohorts of patients undergoing colonoscopy for screening, surveillance, or evaluation of symptoms, we found that diminutive polyps with advanced histologic features do not increase risk for metachronous advanced neoplasia.

A stool test in patients with active ulcerative colitis helps exclude cytomegalovirus disease.

Objectives: In severe ulcerative colitis (UC) bowel biopsy is recommended to detect the cytomegalovirus (CMV) infection capable of complicating the course of the disease. Histopathology with immunohistochemistry (IHC) is time-consuming, and a blood polymerase chain reaction (PCR) for CMV DNA is used as an alternative, notwithstanding nothing more than a moderate correlation between the two. We aimed to detect CMV DNA in the stools of patients with active UC, and to compare the results with CMV IHC in bowel biopsies.Materials and methods: Measurement of CMV DNA in stools (copies/ml) entailed PCR, while biopsies assessed inflammation activity (Geboes scale), as well as counts of numbers of CMV IHC-positive cells/biopsy. The severity of UC was assessed using the Mayo score, stool calprotectin and concentrations of C-reactive protein in the blood.Results: 89 of the above pairs of tests for CMV were performed among 75 patients. CMV was detected in 36/89 stool specimens and 19/89 bowel biopsies. The sensitivity of the stool-CMV PCR was thus 84.7%, while specificity was of 71.4%. The negative predictive value was 94.3% and the positive predictive value 44.4%. No difference in the severity of UC was noted between the stool CMV DNA positive and negative groups. Similarly, there was no difference in the severity of UC between the CMV IHC positive and negative groups, except for the Geboes score, more often found to be higher in CMV IHC-positive patients (p = .002).Conclusions: CMV DNA was detected in the stools of 40.4% of patients with active UC. A negative test result may help to exclude bowel CMV disease.

Endoscopist biopsy rate as a quality indicator for outpatient gastroscopy: a multicenter cohort study with validation.

BACKGROUND AND AIMS: The diagnosis of gastric premalignant conditions (GPCs) relies on endoscopy with mucosal sampling. We hypothesized that the endoscopist biopsy rate (EBR) might constitute a quality indicator for EGD, and we have analyzed its association with GPC detection and the rate of missed gastric cancers (GCs). METHODS: We analyzed EGD databases from 2 high-volume outpatient units. EBR values, defined as the proportion of EGDs with ≥1 biopsy to all examinations were calculated for each endoscopist in Unit A (derivation cohort) and divided by the quartile values into 4 groups. Detection of GPC was calculated for each group and compared using multivariate clustered logistic regression models. Unit B database was used for validation. All patients were followed in the Cancer Registry for missed GCs diagnosed between 1 month and 3 years after EGDs with negative results. RESULTS: Sixteen endoscopists in Unit A performed 17,490 EGDs of which 15,340 (87.7%) were analyzed. EBR quartile values were 22.4% to 36.7% (low EBR), 36.8% to 43.7% (moderate), 43.8% to 51.6% (high), and 51.7% and 65.8% (very-high); median value 43.8%. The odds ratios for the moderate, high, and very-high EBR groups of detecting GPC were 1.6 (95% confidence interval [CI], 1.3-1.9), 2.0 (95% CI, 1.7-2.4), and 2.5 (95% CI, 2.1-2.9), respectively, compared with the low EBR group (P < .001). This association was confirmed with the same thresholds in the validation cohort. Endoscopists with higher EBR (≥43.8%) had a lower risk of missed cancer compared with those in the lower EBR group (odds ratio, 0.44; 95% CI, 0.20-1.00; P = .049). CONCLUSIONS: The EBR parameter is highly variable among endoscopists and is associated with efficacy in GPC detection and the rate of missed GCs.