Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Accuracy of colon capsule endoscopy for advanced neoplasia.

BACKGROUND AND AIMS: Second-generation colon capsule endoscopy (CCE-2) has shown promising accuracy for the diagnosis of overall neoplasia. Advanced neoplasia (AN) represents the main target of colorectal cancer screening programs. Our aim was to assess the diagnostic accuracy of CCE-2 for the detection of AN in patients with a positive result for the fecal immunochemical test (FIT) who are undergoing screening. METHODS: Patients aged 50 to 69 years with a positive result for the FIT in 4 population screening programs in Italy and Spain were enrolled. Screenees were asked to undergo CCE-2, followed by traditional colonoscopy (TC). TC was performed the same day or the following morning. Bowel preparation included a split-dose polyethylene glycol-based regimen, with sodium phosphate (NaP) with gastrografin as boosters. The CCE-2 video was read by an endoscopist blinded to the results of TC. The main outcomes were CCE-2 accuracy in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for AN when using 2 different size thresholds for TC referral (ie, polyps ≥6 mm and ≥10 mm). RESULTS: Two hundred twenty-two patients were enrolled, and 178 patients completed both CCE-2 and TC (87.7%). Overall, 59 cases of AN were detected at TC. CCE-2 sensitivity was 90%, specificity was 66.1%, PPV was 57.4%, and NPV was 92.9% for AN when using a 6-mm cut-off (TC referral rate, 52.8%) and 76.7%, 90.7%, 80.7%, and 88.4% when using a 10-mm cut-off (TC referral rate, 32%), respectively. CCE-2 detected that 8 of 9 already developed colorectal cancers. Among the 41 false positives at the 6-mm cut-off, 34 (82.9%) presented with a nonadvanced adenoma at TC. Mean transit time was 4 hours and 4 minutes, and ≥70% of patients excreted the capsule within 5 hours. CONCLUSIONS: In an enriched disease setting, we showed the high sensitivity of CCE-2 for the diagnosis of AN at a 6-mm cut-off. The apparently low CCE-2 specificity is related to the choice of AN as the main outcome. (Clinical trial registration number: ISRCTN 62158762.).

Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.

INTRODUCTION: Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia. OBJECTIVE: To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels. METHODS: We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia. RESULTS: Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3ng/ml vs. 139.08ng/ml, P<0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6ng/ml vs. 274.3ng/ml, P=0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r=0.5, P<0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173ng/ml and 204ng/ml (AUC=0.80 [95% CI: 0.72-0.86], P<0.001; sensitivity, 80-86% and specificity, 57-67%). CONCLUSION: Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers.

Uptake of Colon Capsule Endoscopy vs Colonoscopy for Screening Relatives of Patients With Colorectal Cancer.

BACKGROUND & AIMS: The efficacy of screening colonoscopy in first-degree relatives (FDRs) of patients with colorectal cancer (CRC) is limited by suboptimal uptake. We compared screening uptake of colon capsule endoscopy (CCE) vs colonoscopy in this population. METHODS: We performed a prospective study of 329 asymptomatic FDRs of patients with CRC who were randomly assigned to groups examined by CCE (PillCam, second generation; n = 165) or colonoscopy (n = 164) at a tertiary hospital in Spain from July 2012 through December 2013. Crossover was permitted for patients who did not wish to undergo the assigned procedure. Subjects assigned to CCE who had a significant lesion (polyp ≥ 10 mm, >2 polyps of any size, or CRC) were invited to undergo colonoscopy. RESULTS: One hundred twenty subjects in the CCE group and 113 in the colonoscopy group were eligible for inclusion. In the intention-to-screen analysis, uptake was similar between groups (55.8% CCE vs 52.2% colonoscopy; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.51-1.44; P = .57); 57.4% of subjects crossed over from the CCE group, and 30.2% crossed over from the colonoscopy group (OR, 3.11; 95% CI, 1.51-6.41; P = .002). Unwillingness to repeat bowel preparation in the case of a positive result was the main reason that subjects assigned to the CCE group crossed over; fear of colonoscopy was the reason that most patients in this group crossed over. A significant lesion was detected in 14 subjects (11.7%) in the CCE group and 13 subjects (11.5%) in the colonoscopy group (OR, 1.02; 95% CI, 0.45-2.26; P = .96). CONCLUSIONS: In a prospective study, similar numbers of FDRs of patients with CRC assigned to undergo CCE or colonoscopy agreed to participate, but most preferred to undergo colonoscopy. CCE was as effective as colonoscopy in detecting significant lesions; it could be a valid rescue strategy for subjects who reject screening colonoscopy. ClinicalTrials.gov number: NCT01557101.

Linitis-like squamous esophageal cancer diagnosed by endoscopic ultrasonography-guided fine-needle aspiration cytology: report of two cases.

Endoscopic ultrasonography-guided fine-needle aspiration cytology (EUS-FNA) may provide full-thickness biopsies, adequate for cytology and histology. In the present case report, we describe the first cases of a rare well-differentiated squamous esophageal carcinoma (verrucous esophageal cancer), finally diagnosed by EUS-FNA using a large FNA needle after several upper endoscopies with biopsies negative for malignancy. In this report, we highlight the usefulness of this procedure and EUS features in the diagnosis of suspicious esophageal lesions with negative endoscopic biopsies for malignancy.

Effects of colon capsule endoscopy on medical decision making in patients with incomplete colonoscopies.

BACKGROUND & AIMS: Colon capsule endoscopy (CCE) is an orally ingested colon imaging tool used to evaluate patients with colonic disease. We evaluated the efficacy of CCE in helping physicians make decisions about patients with incomplete conventional colonoscopies (ICCs). METHODS: In a prospective study, we analyzed data from 34 patients with nonocclusive ICC who were eligible for CCE between May 2010 and April 2011; patients with colectomy, occlusive lesions, or inadequate bowel cleansing for the colonoscopy were excluded. Two experienced observers who were blinded to colonoscopy findings analyzed the CCE data. Four months later, medical records were reviewed to determine the effects of CCE on medical decision making. CCE was considered conclusive when the findings facilitated a medical decision. RESULTS: Bowel cleanliness was good or excellent for 22 patients (64.7%). CCE exceeded the most proximal point reached by conventional colonoscopy in 29 patients (85.3%). CCE findings allowed formulation of a specific medical plan for 20 patients (58.8%); 12 (35.2%) had irrelevant or no lesions, so the study was concluded; 7 (20.5%) underwent polypectomy or surgery for advanced colorectal neoplasia; and 1 (3%) was treated for Crohn's disease. Inconclusive CCEs resulted from poor preparation of the bowel (n = 12) and excessively slow (n = 1) or rapid (n = 1) capsule transit. CONCLUSIONS: CCE might be an alternative procedure to complete colon examination in patients with nonocclusive ICC.