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).

Predictive factors for inadequate bowel cleansing in colon capsule endoscopy / Factores predictores de limpieza colónica inadecuada en exploraciones con cápsula endoscópica de colon

Background and aims: Achieving adequate bowel cleansing is of utmost importance for the efficiency of colon capsule endoscopy (CCE). However, information about predictive factors is lacking. The aim of this study was to assess the predictive factors of poor bowel cleansing in the CCE setting. Methods: In this observational study, 126 patients who underwent CCE at two tertiary care hospitals were included between June 2017 and January 2020. Participants prepared for bowel cleansing with a 1-day clear liquid diet, a 4-L split-dose polyethylene glycol regimen and boosters with sodium phosphate, sodium amidotrizoate and meglumine amidotrizoate. Domperidone tablets and bisacodyl suppositories were administered when needed. Overall and per-segment bowel cleansing was evaluated using a CCE cleansing score. Simple and multiple logistic regression analysis were carried out to assess poor bowel cleansing and excretion rate predictors. Results: Overall bowel cleansing was optimal in 53 patients (50.5%). Optimal per-segment bowel cleansing was achieved as follows: cecum (86 patients; 74.8%), transverse colon (91 patients; 81.3%), distal colon (81 patients; 75%) and rectum (64 patients; 66.7%). In the univariate analysis, elderly (OR, 1.03; 95% CI (1.01–1.076)) and constipation (OR, 3.82; 95% CI (1.50–9.71)) were associated with poor bowel cleansing. In the logistic regression analysis, constipation (OR, 3.77; 95% CI (1.43–10.0)) was associated with poor bowel cleansing. No variables were significantly associated with the CCE device excretion rate. Conclusion: Our results suggest that constipation is the most powerful predictor of poor bowel cleansing in the CCE setting. Tailored cleansing protocols should be recommended for these patients.(AU)

Antecedentes y objetivos Lograr una limpieza intestinal adecuada es de gran importancia para la eficiencia de la cápsula endoscópica de colon (CEC). Se carece de información sobre factores predictivos. El objetivo fue evaluar los factores predictivos de la limpieza colónica deficiente en pacientes con CEC. Métodos: Ciento veintiséis pacientes fueron sometidos a CEC en dos hospitales de tercer nivel entre junio de 2017 y enero de 2020. La preparación consistió en un día de dieta líquida, y 4 l de polietilenglicol (dosis fraccionada), fosfato sódico, amidotrizoato de sodio y meglumina amidotrizoato. Ocasionalmente se administró domperidona y supositorios de bisacodilo. Se evaluó limpieza total y por segmentos. Se realizó un análisis de regresión logística simple y múltiple para evaluar factores de limpieza deficiente y de excreción de la CEC. Resultados: La limpieza intestinal fue óptima en 53 pacientes (50,5%). Por segmentos fue: ciego y ascendente (86 pacientes; 74,8%), transverso (91 pacientes; 81,3%), distal (81 pacientes; el 75%) y recto (64 pacientes; 66,7%). En la regresión simple, la edad avanzada (OR, 1,03, IC 95% [1,01-1,076]) y el estreñimiento (OR, 3,82; IC 95% [1,50-9,71]) se asociaron con una limpieza deficiente. El estreñimiento (OR, 3,77; IC del 95% [1,43-10,0]) fue el único factor asociado de forma independiente. Ninguna variable se asoció a la tasa de excreción de la CEC. Conclusión: Nuestros resultados sugieren que el estreñimiento es el factor más potente de la limpieza deficiente colónica en el estudio endoscópico con CEC. Protocolos de limpieza adaptados se deben recomendar en estos pacientes.(AU)

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 / Metaloproteinasa 9 como biomarcador plasmático de neoplasia colorrectal avanzada

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 292.3 ng/ml vs. 139.08 ng/ml, P < 0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6 ng/ml vs. 274.3 ng/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 173 ng/ml and 204 ng/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

INTRODUCCIÓN: Las metaloproteinasas (MMP) son proteínas que se sobreexpresan en diferentes etapas de la carcinogénesis colorrectal y podrían ser biomarcadores de neoplasia colorrectal. OBJETIVO: Evaluar la utilidad de MMP2 y MMP9 en plasma para detectar neoplasia colorrectal avanzada y su correlación con los niveles tisulares. MÉTODOS: Se analizaron muestras de sangre y tejido en pacientes con adenomas no avanzados (n = 25), adenomas avanzados (n = 25), cáncer colorrectal (n = determinaron mediante tecnología xMAP Luminex y zimografía con gelatina. Se utilizaron curvas ROC para calcular el punto de corte óptimo para neoplasia colorrectal avanzada. RESULTADOS: Los niveles de MMP2 fueron similares en las distintas lesiones. Los niveles de MMP9 fueron significativamente superiores en los pacientes con lesiones neoplásicas comparados con controles sanos (mediana de 292,3 ng/ml vs. 139,08 ng/ml; p < 0,001). Los niveles de MMP9 fueron más altos en los cánceres colorrectales que en adenomas no avanzados (mediana de 314,6 ng/ml vs. 274,3 ng/ml; p = 0,03). Se observó correlación entre los niveles plasmáticos y tisulares de MMP9 (r = 0,5; p < 0,001). El rango de MMP9 plasma con mayor precisión diagnóstica fue 173-204 ng/ml (AUC = 0,80 [IC 95%: 0,72-0,86], p < 0,001; sensibilidad 80-86% y especificidad 57-67%). CONCLUSIÓN: Los niveles en plasma de MMP9 podrían ser un biomarcador útil para detectar neoplasia colorrectal avanzada. La combinación con otros biomarcadores podría aumentar su rendimiento diagnóstico

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.