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1.
World J Gastroenterol ; 27(31): 5272-5287, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497450

RESUMO

BACKGROUND: The rate of positive tests using fecal immunochemical test (FIT) does not decrease with subsequent campaigns, but the positive predictive value of advanced neoplasia significantly decreases in subsequent campaign after a first negative test. A relationship between the fecal hemoglobin concentration (Fhb) and the opportunity to detect a colorectal cancer in subsequent campaign has been shown. AIM: To predict the severity of colorectal lesions based on Fhb measured during previous colorectal cancer screening campaign. METHODS: This etiological study included 293750 patients aged 50-74, living in Auvergne-Rhône-Alpes (France). These patients completed at least two FIT [test(-1) and test(0)] between June 2015 and December 2019. Delay between test(-1) and test(0) was > 1 year and test(-1) result was negative (< 150 ngHb/mL). The severity of colorectal lesions diagnosed at test(0) was described according to Fhb measured at test(-1) [Fhb(-1)]. The relationship between the severity classified in seven ordinal categories and the predictive factors was analyzed in an ordered multivariate polytomous regression model. RESULTS: The test(0) positive rate was 4.0%, and the colonoscopy completion rate was 97.1% in 11594 patients who showed a positive test(0). The colonoscopy detection rate was 77.7% in those 11254 patients who underwent a colonoscopy. A total of 8748 colorectal lesions were detected (including 2182 low-risk-polyps, 2400 high-risk-polyp, and 502 colorectal cancer). The colonoscopy detection rate varied significantly with Fhb(-1) [0 ngHb/mL: 75.6%, (0-50 ngHb/mL): 77.3%, (50-100 ngHb/mL): 88.7%, (100-150 ngHb/mL): 90.3%; P = 0.001]. People with a Fhb(-1) within (100-150 ngHb/mL) (P = 0.001) were 2.6 (2.2; 3.0) times more likely to have a high severity level compared to those having a Fhb(-1) value of zero. This risk was reduced by 20% in patients aged 55-59 compared to those aged < 55 [adjusted odds ratio: 0.8 (0.6; 1.0)]. CONCLUSION: The study showed that higher Fhb(-1) is correlated to an increased risk of severity of colorectal lesions. This risk of severity increased among first-time participants (age < 55) and the elderly (≥ 70). To avoid the loss of chance in these age groups, the FIT positivity threshold should be reduced to 100 ngHb/mL. The other alternative would be to reduce the time between the two tests in these age groups from the current 2 years to 1 year.


Assuntos
Neoplasias Colorretais , Sangue Oculto , Idoso , Pré-Escolar , Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Fezes/química , Hemoglobinas/análise , Humanos , Programas de Rastreamento
2.
BMJ Open ; 11(9): e049581, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489283

RESUMO

OBJECTIVES: To evaluate the cost-effectiveness of four different primary screening strategies: high-risk factor questionnaire (HRFQ) alone, single immunochemical faecal occult blood test (iFOBT), double iFOBT and HRFQ+double iFOBT for colorectal cancer (CRC) screening compared with no screening using the Markov model. METHODS: Treeage Pro V.2011 software was used to simulate the Markov model. The incremental cost-effectiveness ratio, which was compared with the willingness-to-pay (WTP) threshold, was used to reflect the cost-effectiveness of the CRC screening method. One-way sensitivity analysis and probabilistic sensitivity analysis were used for parameter uncertainty. RESULTS: All strategies had greater effectiveness because they had more quality-adjusted life years (QALYs) than no screening. When the WTP was ¥435 762/QALY, all screening strategies were cost-effective compared with no screening. The double iFOBT strategy was the best-buy option compared with all other strategies because it had the most QALYs and the least cost. One-way sensitivity analysis showed that the sensitivity of low-risk adenoma, compliance with colonoscopy and primary screening cost were the main influencing factors comparing single iFOBT, double iFOBT and HRFQ+double iFOBT with no screening. However, within the scope of this study, there was no fundamental impact on cost-effectiveness. Probabilistic sensitivity analysis showed that when the WTP was ¥435 762/QALY, the probabilities of the cost-effectiveness acceptability curve with HRFQ alone, single iFOBT, double iFOBT and HRFQ+double iFOBT were 0.0%, 5.3%, 69.3% and 25.4%, respectively. CONCLUSIONS: All screening strategies for CRC were cost-effective compared with no screening strategy. Double iFOBT was the best-buy option compared with all other strategies. The significant influencing factors were the sensitivity of low-risk polyps, compliance with colonoscopy and cost of primary screening.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , China , Colonoscopia , Neoplasias Colorretais/diagnóstico , Análise Custo-Benefício , Humanos , Cadeias de Markov , Programas de Rastreamento , Sangue Oculto , Anos de Vida Ajustados por Qualidade de Vida
3.
Analyst ; 146(18): 5714-5721, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515700

RESUMO

The molecular diagnosis of KRAS mutations has become crucial for clinical decision-making in colorectal cancer (CRC) treatments. Currently, the common methods for detecting mutations are based on quantitative PCR, DNA sequencing and droplet digital PCR (ddPCR), which require expensive specialized equipment and testing reagents. Herein, we propose a simple and specific strategy by integrating asymmetric PCR with surface-enhanced Raman spectroscopy (Asy-PCR/SERS) for the detection of KRAS G12V mutation, one of the most common driver mutations in CRC. To discriminate mutant targets from non-targets, Asy-PCR was applied to obtain single-stranded DNA (ssDNA) with unequal amounts of forward and reverse primers, subsequently, detection of the target mutant ssDNA amplicons was attempted by hybridization with Raman reporter-coded and allele-specific oligonucleotide-functionalized gold nanoparticles (SERS nanotags). The oligo encoding of the KRAS G12V mutant sequence could be identified by using a portable Raman spectrometer where the characteristic spectra of SERS nanotags indicate the presence of mutant targets. The Asy-PCR/SERS method showed high specificity and sensitivity for identifying as few as 0.1% mutant alleles of KRAS G12V mutation from non-target sequences. Using colorectal polyp biopsies, we demonstrated that Asy-PCR/SERS assay could distinguish KRAS G12V (c.35G > T) and KRAS G12D (c.35G > A) which occur at the same nucleotide location. As KRAS G12V is a driver oncogene in other cancers including lung, pancreatic, ovarian and endometrial cancers, the proposed assay shows great potential for application in additional tumor streams.


Assuntos
Neoplasias Colorretais , Nanopartículas Metálicas , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Ouro , Humanos , Mutação , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas p21(ras)/genética
4.
Sensors (Basel) ; 21(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502594

RESUMO

Colorectal cancer is the second leading cause of cancer death and ranks third worldwide in diagnosed malignant pathologies (1.36 million new cases annually). An increase in the diversity of treatment options as well as a rising population require novel diagnostic tools. Current diagnostics involve critical human thinking, but the decisional process loses accuracy due to the increased number of modulatory factors involved. The proposed computer-aided diagnosis system analyses each colonoscopy and provides predictions that will help the clinician to make the right decisions. Artificial intelligence is included in the system both offline and online image processing tools. Aiming to improve the diagnostic process of colon cancer patients, an application was built that allows the easiest and most intuitive interaction between medical staff and the proposed diagnosis system. The developed tool uses two networks. The first, a convolutional neural network, is capable of classifying eight classes of tissue with a sensitivity of 98.13% and an F1 score of 98.14%, while the second network, based on semantic segmentation, can identify the malignant areas with a Jaccard index of 75.18%. The results could have a direct impact on personalised medicine combining clinical knowledge with the computing power of intelligent algorithms.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Inteligência Artificial , Pólipos do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/diagnóstico , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
5.
Rev Med Chil ; 149(4): 580-590, 2021 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-34479346

RESUMO

Screening programs for colorectal cancer (CRC) are standard in most developed countries because they reduce mortality and are cost-effective. Within them, colonoscopy allows to directly visualize the colon and remove neoplastic lesions. However, it is an expensive exam with low adherence in asymptomatic individuals. The fecal occult blood test (FOBT) is a low-cost and risk-free method for the user, which results in a high rate of adherence, explaining its use in most screening programs. This article analyzes the effectiveness of different fecal occult blood tests in screening programs. The main conclusions are that the sensitivity of the guaiac-based chemical test for the detection of colorectal cancer is lower than that observed with qualitative and quantitative immunological tests. Automated quantitative methods allow objective readings independent of the operator and the reaction reading time, necessary for the analysis of large numbers of samples. The participation rate with immunological FOBTs is higher than with chemical ones, which is why they are preferred by the different countries that have screening programs. The use of quantitative tests allows stratification of symptomatic and asymptomatic patients at higher risk, in the screening programs.


Assuntos
Neoplasias Colorretais , Sangue Oculto , Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Guaiaco , Humanos , Programas de Rastreamento
6.
Artigo em Inglês | MEDLINE | ID: mdl-34501687

RESUMO

The frequency of colorectal cancer (CRC) diagnosis has decreased due to the COVID-19 pandemic. Health system planning is needed to address the backlog of undiagnosed patients. We developed a framework for analyzing barriers to diagnosis and estimating patient volumes under different system relaunch scenarios. This retrospective study included CRC cases from the Alberta Cancer Registry for the pre-pandemic (1 January 2016-4 March 2020) and intra-pandemic (5 March 2020-1 July 2020) periods. The data on all the diagnostic milestones in the year prior to a CRC diagnosis were obtained from administrative health data. The CRC diagnostic pathways were identified, and diagnostic intervals were measured. CRC diagnoses made during hospitalization were used as a proxy for severe disease at presentation. A modified Poisson regression analysis was used to estimate the adjusted relative risk (adjRR) and a 95% confidence interval (CI) for the effect of the pandemic on the risk of hospital-based diagnoses. During the study period, 8254 Albertans were diagnosed with CRC. During the pandemic, diagnosis through asymptomatic screening decreased by 6·5%. The adjRR for hospital-based diagnoses intra-COVID-19 vs. pre-COVID-19 was 1.24 (95% CI: 1.03, 1.49). Colonoscopies were identified as the main bottleneck for CRC diagnoses. To clear the backlog before progression is expected, high-risk subgroups should be targeted to double the colonoscopy yield for CRC diagnosis, along with the need for a 140% increase in monthly colonoscopy volumes for a period of 3 months. Given the substantial health system changes required, it is unlikely that a surge in CRC cases will be diagnosed over the coming months. Administrators in Alberta are using these findings to reduce wait times for CRC diagnoses and monitor progression.


Assuntos
COVID-19 , Neoplasias Colorretais , Alberta/epidemiologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2
7.
Medicina (Kaunas) ; 57(7)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34356963

RESUMO

Background and Objectives: Colonoscopy following an episode of acute diverticulitis is currently recommended to rule out underlying colon cancer. However, a number of studies have debated this recommendation. We aimed to explore whether patients with colonic diverticulosis who experienced an episode of acute diverticulitis had higher prevalence colonic pathologies, essentially colonic adenomas and colorectal carcinoma (CRC) on a follow-up colonoscopy. Materials and Methods: We performed a multicenter retrospective study that included patients with a diagnosis diverticulosis as the control group and allocated patients after diverticulitis according to computed tomography (CT) scan and clinical presentation that had performed colonoscopy within 6 months from the acute diverticulitis episode. We compared the detection rate of colonic pathologic findings in both groups. Results: Overall, 367 patients were included. Of them, 134 patients experienced an episode of diverticulitis vs. 233 patients who did not have diverticulitis. On univariate analysis, there was no difference between all pathological findings (CRC, colonic adenomas; OR (odds ratio) 1.51, p = 0.085), and even for each pathological findings alone, there was no difference (for colonic adenomas, p = 0.07; for CRC, p = 0.87). Further sub-analysis revealed that only male gender (OR 4.03, p = 0.004) and smoking (OR 8.67, p < 0.0001) correlated with colonic adenomas and CRC, while moderate to severe disease was not correlated with colonic pathological findings (OR 0.86, 95% CI (confidence interval) 0.4-1.82, p = 0.68). Conclusions: Post-diverticulitis screening colonoscopy has not found a higher rate of colonic pathological findings, especially colonic neoplasia. Decision to perform colonoscopy after acute diverticulitis should be individualized based on risk stratification of colonic neoplasia.


Assuntos
Adenoma , Carcinoma , Neoplasias do Colo , Neoplasias Colorretais , Doença Diverticular do Colo , Diverticulite , Adenoma/diagnóstico , Adenoma/diagnóstico por imagem , Estudos de Casos e Controles , Neoplasias do Colo/complicações , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/epidemiologia , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/diagnóstico por imagem , Feminino , Humanos , Masculino , Estudos Retrospectivos
8.
Artigo em Inglês | MEDLINE | ID: mdl-34444091

RESUMO

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. Approximately 3-5% of CRCs are associated with hereditary cancer syndromes. Individuals who harbor germline mutations are at an increased risk of developing early onset CRC, as well as extracolonic tumors. Genetic testing can identify genes that cause these syndromes. Early detection could facilitate the initiation of targeted prevention strategies and surveillance for CRC patients and their families. The aim of this study was to determine the cost-effectiveness of CRC genetic testing. We utilized a cross-sectional design to determine the cost-effectiveness of CRC genetic testing as compared to the usual screening method (iFOBT) from the provider's perspective. Data on costs and health-related quality of life (HRQoL) of 200 CRC patients from three specialist general hospitals were collected. A mixed-methods approach of activity-based costing, top-down costing, and extracted information from a clinical pathway was used to estimate provider costs. Patients and family members' HRQoL were measured using the EQ-5D-5L questionnaire. Data from the Malaysian Study on Cancer Survival (MySCan) were used to calculate patient survival. Cost-effectiveness was measured as cost per life-year (LY) and cost per quality-adjusted life-year (QALY). The provider cost for CRC genetic testing was high as compared to that for the current screening method. The current practice for screening is cost-saving as compared to genetic testing. Using a 10-year survival analysis, the estimated number of LYs gained for CRC patients through genetic testing was 0.92 years, and the number of QALYs gained was 1.53 years. The cost per LY gained and cost per QALY gained were calculated. The incremental cost-effectiveness ratio (ICER) showed that genetic testing dominates iFOBT testing. CRC genetic testing is cost-effective and could be considered as routine CRC screening for clinical practice.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Análise Custo-Benefício , Estudos Transversais , Testes Genéticos , Humanos , Anos de Vida Ajustados por Qualidade de Vida
9.
Artigo em Inglês | MEDLINE | ID: mdl-34444122

RESUMO

We investigated factors associated with organised and non-organised colorectal cancer screening using faecal occult blood tests, based on data from 308 municipalities in Flanders (6.6 million residents, 57% of Belgium) during 2015-2017. Logistic regression with generalized estimating equations was used to assess the associations between municipal characteristics and organised and non-organised screening coverages. Factors associated negatively with both organised and non-organised screening: percentage of people aged 70-74 in the target population [OR (odds ratios) = 0.98, 95%CI (confidence interval): 0.97-0.99 and OR = 0.98, 95%CI: 0.96-0.999, respectively]; negatively with organised screening: average income [OR = 0.97, 95%CI: 0.96-0.98], percentage of people with a non-Belgian/Dutch nationality [OR = 0.962, 95%CI: 0.957-0.967]; positively with organised screening: percentages of men in the target population [OR = 1.13, 95%CI: 1.11-1.14], jobseekers [OR = 1.12, 95%CI: 1.09-1.15] and people with at least one general practitioner (GP) visit in the last year [OR = 1.04, 95%CI: 1.03-1.05]; positively with non-organised screening: number of patients per GP [OR = 1.021, 95%CI: 1.016-1.026], percentage of people with a global medical dossier handled by a preferred GP [OR = 1.025, 95%CI: 1.018-1.031]. This study helps to identify the hard-to-reach subpopulations in CRC screening, and highlights the important role of GPs in the process of promoting screening among non-participants and encouraging non-organised participants to switch to organised screening.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento , Sangue Oculto
10.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360768

RESUMO

Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and extended surgery. The clinical usefulness of inflammation-related prognostic biomarkers available from routine blood examination has been reported in many types of cancer, e.g., neutrophil-lymphocyte ratio (NLR), lymphocyte-C-reactive protein ratio (LCR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and so on. Moreover, some scoring systems based on circulating blood cell counts and albumin concentration have been also reported to predict cancer patients' prognosis, such as the Glasgow prognostic score (GPS), systemic inflammation score (SIS), and prognostic nutritional index (PNI). The optimal biomarker and optimal cutoff value of the markers can be different depending on the cancer type. In this review, we summarize the prognostic impact of each inflammation-related marker in CRC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Contagem de Leucócitos , Avaliação Nutricional , Valor Preditivo dos Testes , Prognóstico
11.
Ned Tijdschr Geneeskd ; 1642021 05 12.
Artigo em Holandês | MEDLINE | ID: mdl-34346581

RESUMO

Colonoscopy is the reference standard for the detection of polyps and colorectal cancer (CRC). If during colonoscopy, all colorectal lesions are detected and completely removed, this individual will be long-term protected from CRC. The quality of the colonoscopy procedure is essential for an optimal protective effect. Recently published data of negative colonoscopies within the Polish Colonoscopy Screening Program, with a maximum follow-up of 17.4 years, demonstrated that high-quality colonoscopy was associated with a lower CRC incidence and mortality compared to low-quality colonoscopy. Colonoscopy quality was defined by completeness of colonoscopy, quality of the bowel preparation and number of detected colorectal lesions. These results suggest that the interval after a negative colonoscopy for the next screening might be safely prolonged, preventing unnecessary costs and risks for the patient. The quality of the initial colonoscopy is essential and a high quality will be fundamental for surveillance guidelines in the near future.


Assuntos
Neoplasias Colorretais , Pólipos , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer , Humanos , Programas de Rastreamento
12.
Ned Tijdschr Geneeskd ; 1652021 06 03.
Artigo em Holandês | MEDLINE | ID: mdl-34346603

RESUMO

During colonoscopy, all detected polyps are resected and sent for histopathological assessment by the pathologist to determine the interval for a surveillance colonoscopy. Diminutive polyps (1-5 mm), which constitute up to 60% of all polyps, are rarely malignant (0-0.1%). If it would be possible to predict the histology of these diminutive polyps during colonoscopy, histopathological examination could be omitted. This 'optical diagnosis strategy' by endoscopists could lead to significant cost savings. For safe implementation of this strategy in daily practice, its accuracy must meet minimum thresholds. The development of 'electronic chromoendoscopy' has led to more accurate optical diagnosis. However, research shows that some endoscopists are yet not able to meet the required accuracy thresholds. Due to this variability in accuracy and the absence of an accreditation system implementation of the optical diagnosis strategy in daily practice is still unsuccessful.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Pólipos do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/diagnóstico , Eletrônica , Humanos
13.
Medicine (Baltimore) ; 100(31): e26735, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397813

RESUMO

ABSTRACT: Cancer prevention and control are critical public health concerns. However, the screening uptake and referral rate for colorectal cancer (CRC) in Taiwan remain low. This study focused on the factors influencing whether a patient with a CRC diagnosis chooses to undergo referral follow-up.A cross-sectional research and used the Health Belief Model was method applied in this study. Variables such as demographic factors, CRC diagnosis-related knowledge factors, and health belief factors were employed to investigate the decisive factors that affect the health behavior of patients diagnosed with CRC who test positive on the fecal occult blood test. Study identified prospective participants in Daliao District, Kaohsiung City, Taiwan aged 50 to 75 years. A structured questionnaire was administered to the individuals, and 200 responded. The questionnaires of 100 who went for a referral group and 80 who did not a nonreferral group were analyzed. The questionnaire was reliable and valid, as determined through an expert evaluation and pretest, respectively.Among the 200 participants, T test indicated that those who underwent a referral were significantly more likely to be younger (Age [Mean ±â€ŠSD] n: 62.7, 7.1%; Unreferred group: n: 65.1, 7.0%; Referred group: n:60.7, 6.6%; P ≤ .001), be more educated (P = .002), exercise more (P < .05), and have more family members with cancer (P = .001) or CRC (P < .05). Participants who underwent a referral also had significantly more knowledge (P < .001). Furthermore, those who underwent a referral had significantly perceived greater susceptibility (P < .05), greater benefits (P = .002), and lower barriers (P < .001) of screening; they also received greater encouragement to do so from sources (e.g., clinicians or the media) around them (P = .009).Age, education level, number of family members with cancer or CRC, exercise habits, knowledge of CRC, perceived susceptibility, perceived benefits, perceived barriers, and encouragement from others influence referral behavior. Government policy should focus on older patients and health education, especially in the mass media. Hospitals should also ensure the ease of referrals to lower perceived barriers.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/psicologia , Tomada de Decisões , Detecção Precoce de Câncer/psicologia , Idoso , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estudos Prospectivos , Inquéritos e Questionários , Taiwan
14.
Nat Commun ; 12(1): 4811, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376648

RESUMO

Circulating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50-75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498-0.616) for the ERS and 0.622 (0.564-0.681) for the PRS.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real/métodos , Fatores de Risco
16.
Medicina (Kaunas) ; 57(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34441055

RESUMO

Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI). MSI-H tumors are associated with a high mutation burden. Monoclonal antibodies that block immune checkpoints can induce long-term durable responses in some patients. Pembrolizumab is the first checkpoint inhibitor approved in the EU to treat dMMR-MSI-H metastatic CRC. Materials and Methods: Our study assesses the regional variability of MSI-H colorectal cancer tumors in Romania. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks containing tumor samples from 90 patients diagnosed with colorectal cancer were collected from two tertiary referral Oncology Centers from Romania. Tissues were examined for the expression loss of MMR proteins (MLH1, PMS2, MSH2, MSH6) using immunohistochemistry or MSI status using polymerase chain reaction (PCR), respectively. Results: MSI-H was detected in 19 (21.1%) patients. MSI-H was located more in ascending colon (36.8% vs. 9.9%, p-value = 0.0039) and less in sigmoid (5.3% vs. 33.8%, p-value = 0.0136) than MSS patients. Most patients were stage II for MSI-H (42.1%) as well as for MSS (56.3%), with significant more G1 (40.9% vs. 15.8%, p-value = 0.0427) for MSS patients. Gender, N stage, and M stage were identified as significant prognostic factors in multivariate analysis. MSI status was not a statistically significant predictor neither in univariate analysis nor multivariate analysis. Conclusion: Considering the efficacy of PD-1 inhibitor in metastatic CRC with MSI-H or dMMR, and its recent approval in EU, it is increasingly important to understand the prevalence across tumor stage, histology, and demographics, since our study displayed higher regional MSI-H prevalence (21%) compared to the literature.


Assuntos
Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Detecção Precoce de Câncer , Humanos , Projetos Piloto , Romênia
17.
Artigo em Inglês | MEDLINE | ID: mdl-34360481

RESUMO

Colorectal cancer (CRC)-screening reduces mortality, yet remains underutilized. The use of electronic media (e-media) decision aids improves saliency and fosters informed decision-making. This systematic review aimed to determine the effectiveness of CRC-screening promotion, using e-media decision aids in primary healthcare (PHC) settings. Three databases (MEDLINE, Web of Science, and the Cochrane Library) were searched for eligible studies. Studies that evaluated e-media decision aids compared to usual care or other conditions were selected. Quality was assessed by using Cochrane tools. Their effectiveness was measured by CRC-screening completion rates, and meta-analysis was conducted to calculate the pooled estimates. Ten studies involving 9393 patients were included in this review. Follow-up durations spanned 3-24 months. The two types of decision-aid interventions used were videos and interactive multimedia programs, with durations of 6-15 min. Data from nine feasible studies with low or some risk of bias were synthesized for meta-analysis. A random-effects model revealed that CRC-screening promotion using e-media decision aids were almost twice as likely to have screening completion than their comparisons (OR 1.62, 95% CI: 1.03-2.62, p < 0.05). CRC-screening promotion through e-media has great potential for increasing screening participation in PHC settings. Thus, its development should be prioritized, and it should be integrated into existing programs.


Assuntos
Neoplasias Colorretais , Meios de Comunicação , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer , Humanos , Programas de Rastreamento
19.
Sensors (Basel) ; 21(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34450881

RESUMO

Electronic noses (e-nose) offer potential for the detection of cancer in its early stages. The ability to analyse samples in real time, at a low cost, applying easy-to-use and portable equipment, gives e-noses advantages over other technologies, such as Gas Chromatography-Mass Spectrometry (GC-MS). For diseases such as cancer with a high mortality, a technology that can provide fast results for use in routine clinical applications is important. Colorectal cancer (CRC) is among the highest occurring cancers and has high mortality rates, if diagnosed late. In our study, we investigated the use of portable electronic nose (PEN3), with further analysis using GC-TOF-MS, for the analysis of gases and volatile organic compounds (VOCs) to profile the urinary metabolome of colorectal cancer. We also compared the different cancer stages with non-cancers using the PEN3 and GC-TOF-MS. Results obtained from PEN3, and GC-TOF-MS demonstrated high accuracy for the separation of CRC and non-cancer. PEN3 separated CRC from non-cancerous group with 0.81 AUC (Area Under the Curve). We used data from GC-TOF-MS to obtain a VOC profile for CRC, which identified 23 potential biomarker VOCs for CRC. Thus, the PEN3 and GC-TOF-MS were found to successfully separate the cancer group from the non-cancer group.


Assuntos
Neoplasias Colorretais , Compostos Orgânicos Voláteis , Neoplasias Colorretais/diagnóstico , Nariz Eletrônico , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Metaboloma , Compostos Orgânicos Voláteis/análise
20.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208547

RESUMO

BACKGROUND: Granulin is a secreted, glycosylated peptide-originated by cleavage from a precursor protein-which is involved in cell growth, tumor invasion and angiogenesis. However, the specific prognostic impact of granulin in human colorectal cancer has only been studied to a limited extent. Thus, we wanted to assess the expression of granulin in colorectal cancer patients to evaluate its potential as a prognostic biomarker. METHODS: Expressional differences of granulin in colorectal carcinoma tissue (n = 94) and corresponding healthy colon mucosa were assessed using qRT-PCR. Immunohistochemistry was performed in colorectal cancer specimens (n = 97), corresponding healthy mucosa (n = 47) and colorectal adenomas (n = 19). Subsequently, the results were correlated with histopathological and clinical patients' data. HCT-116 cells were transfected with siRNA for invasion and migration assays. RESULTS: Immunohistochemistry and qRT-PCR revealed tumoral over expression of granulin in colorectal cancer specimens compared to corresponding healthy colon mucosa and adenomas. Tumoral overexpression of granulin was associated with a significantly impaired overall survival. Moreover, downregulation of granulin by siRNA significantly diminished the invasive capacities of HCT-116 cells in vitro. CONCLUSION: Expression of granulin differs in colorectal cancer tissue, adenomas and healthy colon mucosa. Furthermore, granulin features invasive and migrative capabilities and overexpression of granulin correlates with a dismal prognosis. This reveals its potential as a prognostic biomarker and granulin could be a worthwhile molecular target for individualized anticancer therapy.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Granulinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Feminino , Expressão Gênica , Granulinas/genética , Células HCT116 , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
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