M Kerkhof

Grading of dysplasia in Barrett's oesophagus: Substantial interobserver variation between general and gastrointestinal pathologists

Aims:  To determine interobserver variation in grading of dysplasia in Barretts oesophagus (BO) between non‐expert general pathologists and expert gastrointestinal pathologists on the one hand and between expert pathologists on the other hand.

Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)

BACKGROUND Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. OBJECTIVE To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. DESIGN, SETTING, AND PARTICIPANTS We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). INTERVENTION Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. MEASUREMENTS Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. RESULTS AND LIMITATIONS In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. CONCLUSIONS PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.

Predictors for neoplastic progression in patients with Barrett's Esophagus: a prospective cohort study

OBJECTIVES:Patients with Barretts esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors.METHODS:We included 713 patients with BE (≥2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance.RESULTS:After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3–7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01–1.2), esophagitis (RR 3.5; 95% CI 1.3–9.5), and LGD (RR 9.7; 95% CI 4.4–21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18–40%).CONCLUSIONS:In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

Does CDX2 expression predict Barrett's metaplasia in oesophageal columnar epithelium without goblet cells?

Background  Intestinal metaplasia (Barretts oesophagus), but not cardiac‐type mucosa in columnar‐lined oesophagus, is regarded as premalignant. As intestinal metaplasia and cardiac‐type mucosa are endoscopically indiscernible, it is difficult to take targeted samples from columnar‐lined oesophagus with consequently a risk of having undetected intestinal metaplasia.

Effect of the correction for noncompliance and contamination on the estimated reduction of metastatic prostate cancer within a randomized screening trial (ERSPC section Rotterdam).

The European Randomized study of Screening for Prostate Cancer (ERSPC) has recently reported a 20% reduction in death from prostate cancer in a population‐based prostate cancer screening (core age group: 55–69 years of age). The effect of screening may be diluted by noncompliance in the screening arm and contamination by PSA testing in the control arm. The purpose is to analyze the effect of prostate cancer screening on the incidence of metastatic prostate cancer, both with and without adjustment for noncompliance and contamination. We analyzed the occurrence of metastases in 42,376 men aged 55–75 years who were randomized in the Rotterdam section of the ERSPC between 1993 and 1999. Contamination adjustment was based on follow‐up findings and questionnaire data from all men in the control group who developed prostate cancer and from a random sample of 291 men without cancer who had a PSA test. Prostate cancer screening significantly reduced the occurrence of metastatic prostate cancer in the intention‐to‐screen analysis [RR 0.75, 95% CI 0.59–0.95, p = 0.02] and more so in adjusted analyses; contamination adjusted RR 0.73, 95% CI 0.56–0.96; noncompliance adjusted RR 0.72, 95% CI 0.55–0.95 and fully adjusted analysis RR 0.68, 95% CI 0.49–0.94, p = 0.02. In the population of ERSPC Rotterdam (N = 42,376 men), screening reduces the risk to be diagnosed with metastatic prostate cancer considerably on population level, an effect which is even more pronounced in men who are in fact screened.

Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer: A Multicenter Cohort Study

Objectives:The decision to perform secondary surgery after endoscopic resection of T1 colorectal cancer (CRC) depends on the risk of lymph node metastasis and the risk of incomplete resection. We aimed to examine the incidence and risk factors for incomplete endoscopic resection of T1 CRC after a macroscopic radical endoscopic resection.Methods:Data from patients treated between 2000 and 2014 with macroscopic complete endoscopic resection of T1 CRC were collected from 13 hospitals. Incomplete resection was defined as local recurrence at the polypectomy site during follow-up or malignant tissue in the surgically resected specimen in case secondary surgery was performed. Multivariate regression analysis was performed to analyze factors associated with incomplete resection.Results:In total, 877 patients with a median follow-up time of 36.5 months (interquartile range 16.0–68.3) were included, in whom secondary surgery was performed in 358 patients (40.8%). Incomplete resection was observed in 30 patients (3.4%; 95% confidence interval (CI) 2.3–4.6%). Incomplete resection rate was 0.7% (95% CI 0–2.1%) in low-risk T1 CRC vs. 4.4% (95% CI 2.7–6.5%) in high-risk T1 CRC (P=0.04). Overall adverse outcome rate (incomplete resection or metastasis) was 2.1% (95% CI 0–5.0%) in low-risk T1 CRC vs. 11.7% (95% CI 8.8–14.6%) in high-risk T1 CRC (P=0.001). Piecemeal resection (adjusted odds ratio 2.60; 95% CI 1.20–5.61, P=0.02) and non-pedunculated morphology (adjusted odds ratio 2.18; 95% CI 1.01–4.70, P=0.05) were independent risk factors for incomplete resection. Among patients in whom no additional surgery was performed, who developed recurrent cancer, 41.7% (95% CI 20.8–62.5%) died as a result of recurrent cancer.Conclusions:In the absence of histological high-risk factors, a ‘wait-and-see’ policy with limited follow-up is justified. Piecemeal resection and non-pedunculated morphology are independent risk factors for incomplete endoscopic resection of T1 CRC.

SECONDARY ANALYSIS OF THE EUROPEAN RANDOMIZED STUDY OF SCREENING FOR PROSTATE CANCER (ERSPC) - EFFECT OF PROSTATE CANCER SCREENING ON THE DEVELOPMENT OF METASTASES AFTER ADJUSTMENT FOR NON-COMPLIANCE AND CONTAMINATION

INTRODUCTION AND OBJECTIVE: Within a few years the ERSPC forecast to give definitive advice about the implementation of prostate cancer (PC) screening. To assess the effect of PC screening for an individual man who accepts the screening, adjustment for noncompliance and contamination is required. To present the effect of PC screening on the development of metastases. The analysis adjusts for several definitions of noncompliance and for contamination differentiated by screening and diagnostic application. METHODS: The method of Cuzick et al [Stat Med. 1997] is applied to adjust for non-compliance and contamination. The endpoint of this secondary analysis is the occurrence of metastases detected from 1993 through 2007. To differentiate the use of the PSA test in diagnostic and screening applications, we sent questionnaires to the general practitioners concerning a sample of 345 participants. The application of the PSA test in the sample of 345 is extrapolated to the original group of contaminators who tested their PSA minimal once after randomisation (N=5097). RESULTS: The questionnaires resulted in 291 responses (84%). 50.2% of those 291 PSA tests were considered contaminating. The intention-to-screen analysis ( ITS) resulted in a relative risk for screening on metastases of 0.73[95% CI; 0.58;0.93] . Before differentiation of the contaminators the adjusted relative risk to screening is 0.49 (p-value: 0.025). Adjusting the effect of screening on metastases however for noncompliance and contamination, screening resulted in risk reduction of 0.64 [p-value<0.01] (table). Risk screenees and controls of prostate cancer metastases before and after adjustment for non-compliance and contamination.