Proton pump inhibitors reduce the accuracy of faecal immunochemical test for detecting advanced colorectal neoplasia in symptomatic patients

Abstract

BackgroundThe faecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening and for the detection of advanced colorectal neoplasia (AN) in symptomatic patients, but its accuracy could be improved. Our objective was to assess the impact of proton pump inhibitors (PPI) on the accuracy of the FIT in the detection of AN, namely advanced colorectal adenoma and CRC.Methods and findingsWe performed a prospective study of 1002 individuals referred for a diagnostic colonoscopy at Bellvitge University Hospital from September 2011 through to October 2012. An exhaustive interview was performed by a gastroenterologist, prescription drug dispensing database was reviewed and the patient was given a FIT prior to colonoscopy. The positivity threshold of FIT used was ≥ 20 μg Hb/g feces and the main outcome was AN. AN was detected in 13.2% (133) of patients. The accuracy of FIT for detecting AN in the PPI users and non-PPI users were: sensitivity 43.0% vs 65.6%, P = 0.009; specificity 86.9% vs 92.3%, P = 0.010; and, predictive positive value 34.4% vs 55.5%, P = 0.007, respectively. In multivariate analysis, adjusting for potential confounders, PPIs were associated with false positives in AN detection by FIT (OR 1.63 CI 95% 1.02–2.59, P < 0.037). The ROC curve for the FIT in the detection of AN in the PPI users and non-PPI users was 0.68 (CI 95% 0.61–0.76) and 0.85 (CI 95% 0.79–0.90).ConclusionsPPI therapy reduces the accuracy of FIT for detecting AN in symptomatic patients.

Systematic review with meta‐analysis: volatile organic compound analysis to improve faecal immunochemical testing in the detection of colorectal cancer

“…Similarly, the effects of medications were not evaluated in the studies included for FIT meta-analysis. 49 These could have influenced the outcome of this review. Larger diagnostic accuracy studies evaluating sample media and optimising analytical methods are required.…”

Performance of the faecal immunochemical test for the detection of colorectal neoplasms and the role of proton pump inhibitors in their diagnostic accuracy

“…Secondly, in the study by Rodriguez-Alonso et al [17] logistic regression was performed for the false positive and false negative results at a cut-off level of 20 μg/g faeces. Since false positive and false negative rates are dependent on the cut-off value applied, the findings cannot be generalized to other cut-off levels.…”

“…Although PPI exposure resulted in low precision estimates for the FIT, it did not reach a statistically significant level in predicting the outcome – whether CRC from other conditions (all adenoma, other bowel conditions or normal) or advanced neoplasia from other conditions (nonadvanced adenoma, other bowel conditions or normal). A previous study by Rodriguez‐Alonso et al [17] looked at the effect of PPI therapy on performance of the FIT for the detection of CRC and advanced neoplasia. This study showed there was no significant difference between the precision estimates in PPI and non‐PPI groups for the detection of CRC, which was similar to our findings.…”

“…Rodriguez‐Alonso [17] et al found that PPIs were independently associated with lower FIT levels, even after adjusting for age, gender, smoking status, dyslipidaemia, diabetes and nonsteroidal anti‐inflammatory drug and antiplatelet use. Several hypothetical mechanisms have been proposed for PPIs and their influence on FIT results.…”

“…Evidence suggests that only half of the population who undergo colonoscopy following a positive screening test is found to have advanced neoplasia at endoscopic examination [11]. Several studies have attempted to evaluate various factors which could potentially confound the performance of the FIT [gastrointestinal (GI) symptoms, comorbidities, medications, demographics and lifestyle] [12][13][14][15][16][17]. Amongst these, proton pump inhibitors (PPIs) have recently been the subject of detailed consideration.…”