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Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.
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BACKGROUND: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). METHODS: After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed ß-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. RESULTS: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. CONCLUSIONS: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.
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Caderinas , Cateninas , delta Catenina , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Humanos , Masculino , Cateninas/genética , Cateninas/metabolismo , Feminino , Pessoa de Meia-Idade , Adulto , Caderinas/genética , Comunicação Celular , Idade de Início , Antígenos CDRESUMO
AIMS: The World Endoscopy Organization (WEO) recommends that endoscopy units implement a process to identify postcolonoscopy colorectal cancer (PCCRC). The aims of this study were to assess the 3-year PCCRC rate and to perform root-cause analyses and categorization in accordance with the WEO recommendations. PATIENTS AND METHODS: Cases of colorectal cancers (CRCs) in a tertiary care center were retrospectively included from January 2018 to December 2019. The 3-year and 4-year PCCRC rates were calculated. A root-cause analysis and categorization of PCCRCs (interval and type A, B, C noninterval PCCRCs) were performed. The level of agreement between two expert endoscopists was assessed. RESULTS: A total of 530 cases of CRC were included. A total of 33 were deemed PCCRCs (age 75.8±9.5 years; 51.5% women). The 3-year and 4-year PCCRC rates were 3.4% and 4.7%, respectively. The level of agreement between the two endoscopists was acceptable either for the root-cause analysis (k=0.958) or for the categorization (k=0.76). The most plausible explanations of the PCCRCs were 8 "likely new PCCRCs", 1 (4%) "detected, not resected", 3 (12%) "detected, incomplete resection", 8 (32%) "missed lesion, inadequate examination", and 13 (52%) "missed lesion, adequate examination". Most PCCRCs were deemed noninterval Type C PCCRCs (N=17, 51.5%). CONCLUSION: WEO recommendations for root-cause analysis and categorization are useful to detect areas for improvement. Most PCCRCs were avoidable and were likely due to missed lesions during an otherwise adequate examination.
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Colonoscopia , Neoplasias Colorretais , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Estudos Retrospectivos , Prevalência , Fatores de Risco , Fatores de Tempo , Detecção Precoce de CâncerRESUMO
Colonoscopy is the cornerstone examination for colorectal cancer (CRC) screening and it is recommended as the first examination in the context of individuals with high risk of CRC development. Thereby, this examination is of choice in the setting of patients with hereditary CRC syndromes or in patients with long-standing inflammatory bowel disease with colon involvement. However, its role is less clear in the average risk-risk population and in patients with family history of CRC not linked to hereditary CRC syndromes. Despite this, current guidelines, include colonoscopy as alternative for CRC screening either in average risk population with the same evidence level that other screening strategies or in the familial risk population. The present manuscript reviews the clinical evidence on the role of colonoscopy in preventing CRC in different screening settings.
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Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Humanos , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Colonoscopia , Fatores de Risco , Programas de RastreamentoRESUMO
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).
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Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Detecção Precoce de Câncer/métodos , Colonoscopia/métodos , Neoplasias Colorretais/epidemiologia , Fatores de Risco , Irmãos , Programas de Rastreamento/métodosRESUMO
BACKGROUND: Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS: In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS: The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 µg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 µg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS: fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.
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Colonoscopia , Sangue Oculto , Humanos , Estudos Prospectivos , Complexo Antígeno L1 Leucocitário , Encaminhamento e Consulta , Atenção Primária à SaúdeRESUMO
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.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Pólipos , Humanos , Colonoscopia/métodos , Colo , Adenoma/diagnóstico , Adenoma/epidemiologia , Fatores de Risco , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Pólipos do Colo/cirurgia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologiaRESUMO
BACKGROUND AND AIMS: Artificial intelligence-based computer-aid detection (CADe) devices have been recently tested in colonoscopies, increasing the adenoma detection rate (ADR), mainly in Asian populations. However, evidence for the benefit of these devices in the occidental population is still low. We tested a new CADe device, namely, ENDO-AID (OIP-1) (Olympus, Tokyo, Japan), in clinical practice. METHODS: This randomized controlled trial included 370 consecutive patients who were randomized 1:1 to CADe (n = 185) versus standard exploration (n = 185) from November 2021 to January 2022. The primary endpoint was the ADR. Advanced adenoma was defined as ≥10 mm, harboring high-grade dysplasia, or with a villous pattern. Otherwise, the adenoma was nonadvanced. ADR was assessed in both groups stratified by endoscopist ADR and colon cleansing. RESULTS: In the intention-to-treat analysis, the ADR was 55.1% (102/185) in the CADe group and 43.8% (81/185) in the control group (P = .029). Nonadvanced ADRs (54.8% vs 40.8%, P = .01) and flat ADRs (39.4 vs 24.8, P = .006), polyp detection rate (67.1% vs 51%; P = .004), and number of adenomas per colonoscopy were significantly higher in the CADe group than in the control group (median [25th-75th percentile], 1 [0-2] vs 0 [0-1.5], respectively; P = .014). No significant differences were found in serrated ADR. After stratification by endoscopist and bowel cleansing, no statistically significant differences in ADR were found. CONCLUSIONS: Colonoscopy assisted by ENDO-AID (OIP-1) increases ADR and number of adenomas per colonoscopy, suggesting it may aid in the detection of colorectal neoplastic lesions, especially because of its detection of diminutive and flat adenomas. (Clinical trial registration number: NCT04945044.).
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Pólipos , Humanos , Inteligência Artificial , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/epidemiologia , Colonoscopia , Pólipos/diagnóstico , Adenoma/diagnóstico por imagem , Adenoma/epidemiologia , Pólipos do Colo/diagnóstico por imagemRESUMO
BACKGROUND & AIMS: Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC. METHODS: A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays. RESULTS: In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity. CONCLUSIONS: Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.
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MicroRNA Circulante , Neoplasias Colorretais , MicroRNAs , Humanos , Biomarcadores Tumorais/genética , Curva ROC , MicroRNAs/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Biópsia Líquida , Perfilação da Expressão GênicaRESUMO
Serrated polyposis syndrome (SPS) is associated with a high risk for colorectal cancer. Intense promoter hypermethylation is a frequent molecular finding in the serrated pathway and may be present in normal mucosa, predisposing to the formation of serrated lesions. To identify novel biomarkers for SPS, fresh-frozen samples of normal mucosa from 50 patients with SPS and 19 healthy individuals were analyzed by using the 850K BeadChip Technology (Infinium). Aberrant methylation levels were correlated with gene expression using a next-generation transcriptome profiling tool. Two validation steps were performed on independent cohorts: first, on formalin-fixed, paraffin-embedded tissue of the normal mucosa; and second, on 24 serrated lesions. The most frequently hypermethylated genes were HLA-F, SLFN12, HLA-DMA, and RARRES3; and the most frequently hypomethylated genes were PIWIL1 and ANK3 (Δß = 10%; P < 0.05). Expression levels of HLA-F, SLFN12, and HLA-DMA were significantly different between SPS patients and healthy individuals and correlated well with the methylation status of the corresponding differentially methylated region (fold change, >20%; r > 0.55; P < 0.001). Significant hypermethylation of CpGs in the gene body of HLA-F was also found in serrated lesions (Δß = 23%; false discovery rate = 0.01). Epigenome-wide methylation profiling has revealed numerous differentially methylated CpGs in normal mucosa from SPS patients. Significant hypermethylation of HLA-F is a novel biomarker candidate for SPS.
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Polipose Adenomatosa do Colo , Neoplasias Colorretais , Polipose Adenomatosa do Colo/genética , Proteínas Argonautas/genética , Biomarcadores , Neoplasias Colorretais/genética , Metilação de DNA/genética , Epigenoma , Antígenos de Histocompatibilidade Classe I , Humanos , Mucosa/patologiaRESUMO
INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.
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Adenoma , Colite Ulcerativa , MicroRNAs , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/genética , Biomarcadores/metabolismo , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
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.
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Bisacodil , Endoscopia por Cápsula , Idoso , Catárticos , Colo , Colonoscopia/métodos , Constipação Intestinal/etiologia , Diatrizoato de Meglumina , Domperidona , Humanos , Polietilenoglicóis , Sódio , SupositóriosRESUMO
INTRODUCTION: Unlike colorectal cancer (CRC), few studies have explored the predictive value of genetic risk scores (GRS) in the development of colorectal adenomas (CRA), either alone or in combination with other demographic and clinical factors. METHODS: In this study, genomic DNA from 613 Spanish Caucasian patients with CRA and 829 polyp-free individuals was genotyped for 88 single-nucleotide polymorphisms (SNPs) associated with CRC risk using the MassArray™ (Sequenom) platform. After applying a multivariate logistic regression model, five SNPs were selected to calculate the GRS. Regression models adjusted by sex, age, family history of CRC, chronic use of NSAIDs, low-dose ASA, and consumption of tobacco were built in order to study the association between GRS and CRA risk. We evaluated the discriminatory capacity using the area under the receiver operating characteristic curve (AUC). The interactions between demographic information and GRS were also analyzed. RESULTS: Significant associations between high GRS values and risk of CRA for analyzed models were observed. In particular, patients with higher GRS values had 2.3-2.6-fold increase in risk of CRA compared to patients with middle values. Combining sex and age with the GRS significantly increased the discriminatory accuracy of the univariate model with GRS alone. The best model achieved an AUC value of 0.665 (95% CI: 0.63-0.69). The GRS showed a different behavior depending on sex and age. CONCLUSION: Our findings showed that, besides sex and age, GRS is an important risk factor for development of CRA and may be useful for CRC risk stratification and adaptation of screening programs.
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Adenoma , Neoplasias Colorretais , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/genética , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
BACKGROUND: Nonadherence to medication is common in patients with inflammatory bowel disease (IBD) and can result in disease complications, therapy escalation, and the need for corticosteroids. The aim of this study was to assess the adherence to self-administered subcutaneous biologic medications prescribed for IBD and to identify the risk factors for nonadherence. METHODS: A retrospective cohort study on IBD patients initiated on subcutaneous biologic therapy between January 2016 and July 2019 was performed. Medical records were retrospectively reviewed for collection of demographic and IBD data. Medication possession ratios (mMPRs) during the first 12 months of treatment and at the end of the follow-up period (global, 42 months) were calculated. Nonadherence was defined as an mMPR of <90%. Multiple regression analysis was performed to assess the risk factors for nonadherence to therapy. RESULTS: A total of 154 patients (84 male and 70 female; mean age at biologic treatment initiation, 36±14 years; Crohn's disease, n=118; ulcerative colitis, n=31; indeterminate colitis, n=5) were included; 121 received adalimumab (ADA) and 33 received ustekinumab (UST); 63% were naive to anti-TNF therapy, while 16.9% previously received more than two biologic treatments. Mean time from IBD diagnosis to subcutaneous biological agent use was 16±10 months. Mean duration of subcutaneous agent use was 17.6 (SD, 11.0) and 17.08 (SD, 6.8) months for ADA and UST, respectively. Global nonadherence (mMPR≤90%) rate was 6.6% for all patients receiving subcutaneous treatment, 6.3% for ADA, and 6.5% for UST. Nonadherence during the first 12 months of treatment (n=98) was 6.1% for all patients, 2.7% for ADA, and 16% for UST. In the multivariate analysis, UST use was independently associated with higher nonadherence only within the first 12 months (OR, 6.7; 95% CI, 1.1-39.5). CONCLUSIONS: High global adherence to self-administered subcutaneous biologic treatment was shown in our study, with higher rates of adherence to ADA than to UST within the first 12 months.
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Produtos Biológicos , Doenças Inflamatórias Intestinais , Adalimumab/uso terapêutico , Produtos Biológicos/uso terapêutico , Doença Crônica , Feminino , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Adesão à Medicação , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral , Ustekinumab/uso terapêuticoRESUMO
Objective: We tested the hypothesis that an enhanced bowel preparation strategy (EBS) improves colonic cleansing in patients at high risk for inadequate bowel cleansing (HRI). Methods: This prospective randomized clinical trial included consecutive HRI patients referred for outpatient colonoscopy between February and October 2019. HRI was considered if patients scored >1.225 according to a previously validated bowel-cleansing predictive score. HRI patients were randomized (1:1) to a low-volume conventional bowel cleansing strategy (CBS) (1-day low residue diet (LRD) plus 2 L of polyethylene glycol (PEG) plus ascorbic acid) or to an EBS (3-day LRD plus 10 mg oral bisacodyl plus 4 L PEG). The Boston Bowel Preparation Scale (BBPS) was used to assess the quality of cleanliness. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. A sample size of 130 patients per group was estimated to reach a 15% difference in favor of EBP. Results: A total of 253 HRI patients were included (mean age 69.8 ± 9.5 years, 51.8% women). No statistically significant differences were found in the BBPS scale between the two groups in the ITT analysis (CBS 76.8% vs. EBS 79.7%, P = 0.58) or PP analysis (CBS 78% vs. EBS 84.3%, P = 0.21), risk difference 2.9% (95% CI-7.26 to 39.16) in the ITT analysis, or risk difference 6.3% (95% CI-3.48 to 16.08) in PP analysis. No differences in preparation tolerance, compliance, adverse effects, or colonoscopy findings were found. Conclusion: EBS is not superior to CBS in hard-to-prepare patients. (EUDRACT: 2017-000787-15, NCT03830489). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03830489.
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INTRODUCTION: Epidemiological studies estimate that having a first-degree relative (FDR) with colorectal cancer (CRC) increases 2-fold to 3-fold the risk of developing the disease. Because FDRs of CRC patients are more likely to co-inherit CRC risk variants, we aimed to evaluate potential differences in genotype distribution of single nucleotide polymorphisms (SNPs) related to CRC risk between FDRs of patients with nonsyndromic CRC (cases) and individuals with no family history of CRC (controls). METHODS: We designed a case-control study comprising 750 cases and 750 Spanish Caucasian controls matched by sex, age, and histological findings after colonoscopy. Genomic DNA from all participants was genotyped for 88 SNPs associated with CRC risk using the MassArray (Sequenom) platform. RESULTS: Ten of the 88 SNPs analyzed revealed significant associations (P < 0.05) with a family history of CRC in our population. The most robust associations were found for the rs17094983G>A SNP in the long noncoding RNA LINC01500 (odds ratio = 0.72; 95% confidence interval: 0.58-0.88, log-additive model), and the rs11255841T>A SNP in the long noncoding RNA LINC00709 (odds ratio = 2.04; 95% confidence interval: 1.19-3.51, dominant model). Of interest, the observed associations were in the same direction than those reported for CRC risk. DISCUSSION: FDRs of CRC patients show significant differences in genotype distribution of SNPs related to CRC risk as compared to individuals with no family history of CRC. Genotyping of CRC risk variants in FDRs of CRC patients may help to identify subjects at risk that would benefit from stricter surveillance and CRC screening programs.
Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Recent evidence suggests that the number of low residue diet (LRD) days does not influence the bowel cleansing quality in non-selected patients. However, there are not data in the subgroup of patients with risk factors of inadequate bowel cleansing. OBJECTIVE: The aim of this study was to assess whether a 3-day LRD improved the bowel cleansing quality in patients with risk factors of poor bowel cleansing. PATIENTS AND METHODS: Post hoc analysis of a randomized controlled trial carried out between December 2017 and March 2018 in a tertiary care hospital. Patients with high risk of poor bowel cleansing were selected following a validated score. The patients were randomized to the 1-day LRD or 3-day LRD groups. All patients received a 2-L split-dose of polyethylene glycol plus ascorbic acid. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted for the main outcome. RESULTS: 135 patients (1-day LRD group=67, 3-day LRD=68) were included. The rate of adequate cleansing quality was not significantly different between the groups in the ITT analysis: 76.1%, 95% CI: [64.6-84.8] vs. 79.4%, 95% CI: [68.2-87.4]; odds ratio (OR) 1.2, 95% CI [0.54-2.73]) or in the PP analysis: 77.3%, 95% CI: [65.7-85.8] vs. 80.3%, 95% CI: [69.0-88.3]; OR 1.2, 95% CI [0.52-2.77]). Compliance with the diet or cleansing solution, satisfaction or difficulties with the LRD and the polyp/adenoma detection rates were not significantly different. CONCLUSION: Our results suggest that 1-day LRD is not inferior to 3-day LRD in patients with risk factors of inadequate bowel cleansing.
Assuntos
Ácido Ascórbico/administração & dosagem , Catárticos/administração & dosagem , Colonoscopia , Dieta/métodos , Fibras na Dieta , Polietilenoglicóis/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Período Pré-Operatório , Estudos Prospectivos , Método Simples-Cego , Fatores de TempoRESUMO
The following recommendations for post-polypectomy colonoscopic surveillance apply to all patients who had one or more polyps that were completely removed during a high quality baseline colonoscopy. 1: ESGE recommends that patients with complete removal of 1â-â4 <â10âmm adenomas with low grade dysplasia, irrespective of villous components, or any serrated polyp <â10âmm without dysplasia, do not require endoscopic surveillance and should be returned to screening.Strong recommendation, moderate quality evidence.If organized screening is not available, repetition of colonoscopy 10 years after the index procedure is recommended.Strong recommendation, moderate quality evidence. 2: ESGE recommends surveillance colonoscopy after 3 years for patients with complete removal of at least 1 adenoma ≥â10âmm or with high grade dysplasia, or ≥â5 adenomas, or any serrated polyp ≥â10âmm or with dysplasia. Strong recommendation, moderate quality evidence. 3: ESGE recommends a 3â-â6-month early repeat colonoscopy following piecemeal endoscopic resection of polyps ≥â20âmm.Strong recommendation, moderate quality evidence. A first surveillance colonoscopy 12 months after the repeat colonoscopy is recommended to detect late recurrence.Strong recommendation, high quality evidence. 4: If no polyps requiring surveillance are detected at the first surveillance colonoscopy, ESGE suggests to perform a second surveillance colonoscopy after 5 years. Weak recommendation, low quality evidence.After that, if no polyps requiring surveillance are detected, patients can be returned to screening. 5: ESGE suggests that, if polyps requiring surveillance are detected at first or subsequent surveillance examinations, surveillance colonoscopy may be performed at 3 years. Weak recommendation, low quality evidence.A flowchart showing the recommended surveillance intervals is provided (Fig.â1).
Assuntos
Adenoma , Pólipos do Colo , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/cirurgia , Colonoscopia , Endoscopia Gastrointestinal , HumanosRESUMO
INTRODUCTION: Cure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern. The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. MATERIALS AND METHODS: Multicentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. RESULTS: One-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DISCUSSION: Gastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.