Diagnostic accuracy of quantitative fecal immunochemical tests for colorectal cancer detection in patients with digestive symptoms

El cáncer colorrectal (CCR) es la cuarta neoplasia maligna más frecuente en todo el mundo y la quinta causa de muerte por cáncer, con un impacto creciente en los países desarrollados. Las autoridades sanitarias han desarrollado dos estrategias principales para reducir las consecuencias del CCR: el cribado poblacional y la detección temprana en pacientes con síntomas. El cribado poblacional ha tenido éxito en la reducción de la mortalidad por CCR aumentando la proporción de pacientes diagnosticados en fases tempranas de la enfermedad y facilitando la detección y eliminación de lesiones pre-neoplásicas. Desafortunadamente la mayor parte de CCR son diagnosticados fuera de los programas de cribado en pacientes con síntomas. Tres metaanálisis han demostrado que varios síntomas como la rectorragia o los cambios de hábito intestinal se asocian con la presencia de CCR. Sin embargo, estos síntomas también son frecuentes dentro de las personas sin enfermedad, siendo en consecuencia poco útiles para ayudar a los médicos en la toma de decisiones. El test de sangre oculta en heces inmunológico cuantitativo (SOHi) ha demostrado presentar una adecuada precisión diagnóstica en el entorno de cribado de sujetos asintomáticos, por lo que es la estrategia de cribado preferida en Europa en el momento actual y recientemente the National Institute for Health and Care Excellence (NICE) ha recomendado su adopción como guía en la toma de decisiones para valorar el origen de síntomas digestivos. Dado que la precisión de una prueba diagnóstica puede modificarse en diferentes contextos es importante conocer si la sensibilidad y especificidad de la SOHi en el entorno del estudio de pacientes con síntomas mantienen valores adecuados para este propósito. Los objetivos de este proyecto son: -Realizar una revisión sistemática y en caso de ser posible un metaanálisis de aquellos trabajos que han estudiado la precisión de SOHi en pacientes con síntomas digestivos. -Comprobar si la precisión obtenida se corresponde con los resultados en vida real hasta la fecha. -Estudiar el pronóstico de una muestra de sujetos con sangre oculta en heces positiva sin CCR para conocer las implicaciones de un falso positivo en el test.O cancro colorrectal (CCR) é a cuarta neoplasia maligna máis frecuente en todo o mundo e a quinta causa de morte por cancro, cun impacto crecente nos países desenvoltos. As autoridades sanitarias deseñaron dúas estratexias principais para reducilas consecuencias do CCR: o cribado poboacional e a detección temperá en doentes con síntomas. O cribado poboacional tivo éxito na redución da mortalidade por CCR aumentando a proporción de doentes diagnosticados en fases temperás da enfermidade e facilitando a detección e eliminación de lesións pre-neoplásicas. Por desgraza a maior parte de CCR son diagnosticados fóra dos programas de cribado en doentes con síntomas. Tres metaanálisis amosaron que varios síntomas como a rectorraxia ou os cambios do hábito intestinal asócianse coa presenza de CCR. Agora ben, estes síntomas tamén son habituais nas persoas sen enfermidade, polo que non teñen moita utilidade para axudar aos médicos na toma de decisións. O test de sangue oculto en feces inmunolóxico cuantitativo (SOHi) demostrou presentar unha adecuada precisión diagnóstica no contexto do cribado de suxeitos asintomáticos, polo que é a estratexia de cribado preferida en Europa no momento actual, e recentemente, the National Institute for Health and Care Excellence ( NICE) recomendou a súa adopción como guía na toma de decisións para valorala orixe de síntomas dixestivos. Dado que a precisión dunha proba diagnóstica pode modificarse en diferentes contextos é importante coñecer se a sensibilidade e especificidade da SOHi no caso do estudo de pacientes con síntomas manteñen valores adecuados para este propósito. Os obxectivos deste proxecto son: -Realizar unha revisión sistemática, e en caso de ser posible unha metanálise daqueles traballos que estudaron a precisión do SOHi en pacientes con síntomas dixestivos. -Comprobar se a precisión obtida correspóndese cos resultados na vida real ata o presente. -Estudar o prognóstico dunha mostra de suxeitos con sangue oculto en feces positivo sen CCR para coñecer as implicacións dun falso positivo no test.Colorectal cancer (CRC) is the fourth most common cancer worldwide and the fifth leading cause of cancer-related death with an increased impact in developed countries. Health authorities have developed two main strategies to reduce the impact of CRC: screening in average and, on occasion, high-risk (personal or family history of CRC or adenomas) populations, and prompt detection in symptomatic patients. CRC screening has been successful in reducing the incidence and mortality of CRC both by increasing the proportion of patients diagnosed at an early stage and by facilitating the removal of pre-neoplastic lesions. Unfortunately, most of CRC are still diagnosed out of the CRC screening programs in symptomatic patients. Three previous meta-analyses have shown that individual symptoms, such as rectal bleeding and changes in bowel habits, may be associated with CRC, however, these symptoms are also frequent in populations without cancer and, therefore, yield poor sensitivity for CRC detection. As a result, identifying which primary care patients should be referred for diagnostic investigation remains challenging. The quantitative faecal immunochemical test (FIT) has demonstrated an adequate diagnostic accuracy for CRC detection in a CRC screening setting, thus being the preferred strategy for CRC screening in Europe at present. Recently, the National Institute for Health and Care Excellence (NICE) has recommended the adoption of FIT in primary care to guide referral for suspected colorectal cancer in people who have abdominal symptoms. Given that diagnostic test accuracy could change due to clinical variability, it is important to estimate FIT´s sensitivity and specificity out of screening setting. The aim of this project is: -To perform a systematic review and, if possible, a meta-analysis including all the diagnostic tests studies that evaluated symptomatic patients. -To compare previously named FIT accuracy with the estimated one using real life data. -To study the prognosis of a sample of subjects with a positive determination of fecal occult blood test without CRC in order to find out the consequences of a FIT false positive

Barreras y beneficios percibidos en la participación en el cribado de cáncer de colon mediante test de sangre oculta en heces

[Abstract] Background: Colorectal cancer is the second cancer-related cause of death in the world. Tumour stage at diagnosis is the principal prognosis factor of survival. However, the participation in the programme is around 50%. The aim of the study was to identify the benefits and barriers perceived by the population when participating in a colorectal cancer screening programme with faecal occult blood test. Methods: We carried out a cases-controls study with 408 participants. We analyzed epidemiological and social variables associated with lifestyle and behavioural factors based in the Health Belief Model. We conducted a descriptive analysis, and identified variables associated to adherence by a logistic regression. Results: Variables independently associated with the participation in a colorectal cancer screening programme were age (OR 1.06; 95% CI: 1.01-1.11), having a stable partner (OR 1.96; 95% CI: 1.20-3.18), the level of education (OR 1.59; 95% CI: 1.02-2.47) and two of the barriers to participate in the faecal occult blood test screening: "you don't know how to do one" (OR=0.46; 95% CI: 0.23-0.93) and "it is not that important right now" (OR=0.43; 95% CI: 0.24-0.78). Conclusion: The existing barriers for screening with faecal occult blood test are the best factor predicting. This is relevant when designing the intervention programmes, as they should focus on reducing perceived barriers to increase the participation in colorectal cancer screening, thereby reducing colorectal cancer mortality.[Resumen] Antecedentes. El cáncer colorrectal constituye la segunda causa de muerte por cáncer en el mundo. El estadio del tumor al diagnóstico es el principal factor pronóstico de supervivencia. Sin embargo, la participación en el programa está en torno al 50%. El objetivo de este estudio fue identificar los beneficios y las barreras percibidos por la población al participar en un programa de cribado de cáncer de colon mediante el test de sangre oculta en heces. Métodos. Estudio de casos y controles con 408 participantes en el que analizamos variables sociodemográficas, variables asociadas al estilo de vida y factores conductuales basados en el Modelo de Creencias en Salud. Realizamos un análisis descriptivo y, para identificar las variables asociadas a la adhesión al programa de cribado de cáncer colorrectal, una regresión logística. Resultados. Las variables que se asociaron de forma independiente a la participación en el programa fueron la edad (OR 1,06; IC 95% 1,01-1,11), tener pareja estable (OR 1,96; IC 95% 1,20-3,18), el nivel de estudios (OR 1,59; IC 95% 1,02-2,47) y 2 de las barreras para participar en el cribado mediante test de sangre oculta en heces: «no sabe cómo hacerlo» (OR 0,46; IC 95% 0,23-0,93) y «no es un problema importante en el momento actual» (OR 0,3; IC 95% 0,24-0,78). Conclusión. Las barreras existentes para el cribado mediante test de sangre oculta en heces son el mejor factor predictivo de participación. Esto es importante a la hora de diseñar los programas de cribado de cáncer colorrectal, ya que la reducción de las barreras percibidas aumentará la participación en los mismos, reduciendo así la mortalidad por cáncer de colon

Risk of gastrointestinal cancer in a symptomatic cohort after a complete colonoscopy: Role of faecal immunochemical test

BACKGROUND: Faecal immunochemical test (FIT) has been recommended to assess symptomatic patients for colorectal cancer (CRC) detection. Nevertheless, some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized. A positive FIT result could be related to other gastrointestinal cancers (GIC). AIM To assess the risk of GIC detection and related death in FIT-positive symptomatic patients (threshold 10 mu g Hb/g faeces) without CRC. METHODS: Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection. Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare, underwent a quantitative FIT before undergoing a complete colonoscopy. Patients without CRC were divided into two groups (positive and negative FIT) using the threshold of 10 mu g Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research. We determined the cumulative risk of GIC, CRC and upper GIC. Hazard rate (HR) was calculated adjusted by age, sex and presence of significant colonic lesion. RESULTS: We included 2709 patients without CRC and a complete baseline colonoscopy, 730 (26.9%) with FIT >= 10 mu gr Hb/gr. During a mean time of 45.5 +/- 20.0 mo, a GIC was detected in 57 (2.1%) patients: An upper GIC in 35 (1.3%) and a CRC in 14 (0.5%). Thirty-six patients (1.3%) died due to GIC: 22 (0.8%) due to an upper GIC and 9 (0.3%) due to CRC. FIT-positive subjects showed a higher CRC risk (HR 3.8, 95%CI: 1.2-11.9) with no differences in GIC (HR 1.5, 95%CI: 0.8-2.7) or upper GIC risk (HR 1.0, 95%CI: 0.5-2.2). Patients with a positive FIT had only an increased risk of CRC-related death (HR 10.8, 95%CI: 2.1-57.1) and GIC-related death (HR 2.2, 95%CI: 1.1-4.3), with no differences in upper GIC-related death (HR 1.4, 95%CI: 0.6-3.3). An upper GIC was detected in 22 (0.8%) patients during the first year. Two variables were independently associated: anaemia (OR 5.6, 95%CI: 2.2-13.9) and age >= 70 years (OR 2.7, 95%CI: 1.1-7.0). CONCLUSION Symptomatic patients without CRC have a moderate risk increase in upper GIC, regardless of the FIT result. Patients with a positive FIT have an increased risk of post-colonoscopy CRC

Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 ± 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3–3.1), CRC (HR 4.4, 95% CI 1.1–17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0–2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3–5.8), rectal bleeding (OR 0.3, 95% CI 0.1–0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7–7.1). However, CEA was increased only in 31.8% (95% CI, 16.4–52.7%) and 50% (95% CI, 25.4–74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRCThis work was supported by Spain’s Carlos III Healthcare Institute by means of project PI17/00837 (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future

High-risk symptoms and quantitative faecal immunochemical test accuracy: systematic review and meta-analysis

BACKGROUND The quantitative faecal immunochemical test for haemoglobin (FIT) has been revealed to be highly accurate for colorectal cancer (CRC) detection not only in a screening setting, but also in the assessment of patients presenting lower bowel symptoms. Therefore, the National Institute for Health and Care Excellence has recommended the adoption of FIT in primary care to guide referral for suspected CRC in low-risk symptomatic patients using a 10 µg Hb/g faeces threshold. Nevertheless, it is unknown whether FIT´s accuracy remains stable throughout the broad spectrum of possible symptoms. AIM To perform a systematic review and meta-analysis to assess FIT accuracy for CRC detection in different clinical settings. METHODS A systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2018 to conduct a meta-analysis of prospective studies including symptomatic patients that evaluated the diagnostic accuracy of quantitative FIT for CRC detection. Studies were classified on the basis of brand, threshold of faecal haemoglobin concentration for a positive test result, percentage of reported symptoms (solely symptomatic, mixed cohorts) and CRC prevalence (< 2.5%, ≥ 2.5%) to limit heterogeneity and perform subgroup analysis to assess the influence of clinical spectrum on FIT´s accuracy to detect CRC. RESULTS Fifteen cohorts including 13073 patients (CRC prevalence 0.4% to 16.8%) were identified. Pooled estimates of sensitivity for studies using OC-Sensor at 10 µg Hb/g faeces threshold (n = 10400) was 89.6% [95% confidence interval (CI): 82.7% to 94.0%). However, pooled estimates of sensitivity for studies formed solely by symptomatic patients (n = 4035) and mixed cohorts (n = 6365) were 94.1% (95%CI: 90.0% to 96.6%) and 85.5% (95%CI: 76.5% to 91.4%) respectively (P < 0.01), while there were no statistically significant differences between pooled sensitivity of studies with CRC prevalence < 2.5% (84.9%, 95%CI: 73.4% to 92.0%) and ≥ 2.5% (91.7%, 95%CI: 83.3% to 96.1%) (P = 0.25). At the same threshold, OC-Sensor® sensitivity to rule out any significant colonic lesion was 78.6% (95%CI: 75.6% to 81.4%). We found substantial heterogeneity especially when assessing specificity. CONCLUSION The results of this meta-analysis confirm that, regardless of CRC prevalence, quantitative FIT is highly sensitive for CRC detection. However, FIT ability to rule out CRC is higher in studies solely including symptomatic patient

Hepatocarcinoma: estado actual

Hepatocellular carcinoma ranks among the most common primary liver malignancy and the sixth most frequently diagnosed cancer worldwide. More than 500.000 cases are diagnosed each year making this pathology the third leading cause of cancer-related death in the world. This disease affects almost exclusively to chronic liver patients who have developed cirrhosis, especially the one related to hepatitis B and C virus infection. Hepatocellular carcinoma is the leading cause of death in this group. The incidence of Hepatocellular carcinoma varies widely according to geographic location. Incidence rates from 2 to more than 50 cases per 100.000 inhabitants per year have been described. These differences in the distribution of HC are probably due to regional variations in the exposure to different risk factors and viral genotypes. The most prevalent areas include Southeastern Asia and Sub-Saharan Africa where hepatitis B viral infection is endemic. The hepatocellular carcinoma incidence is increasing worldwide. This includes western countries due to the increased spread of hepatitis C virusinfection in the mid 1960s and 1970s, combined with an increase in excesive alcohol consumption in that area. The high complexity that distiguish both this neoplasm and the pathology which has been closely related to, deserves a multidisciplinary approach with multiple medical and surgical specialties to guarantee an appropiate management.El carcinoma hepatocelular (CHC) es la neoplasia primaria hepática más frecuente. Constituye el sexto tumor más habitual en el mundo, con más de 500.000 casos diagnosticados cada año y es la tercera causa más común de muerte por cáncer. Esta enfermedad afecta de manera casi exclusiva a pacientes con hepatopatía crónica que han desarrollado cirrosis, especialmente la relacionada con los virus de la hepatitis B y C, siendo en este grupo de sujetos el CHC la causa más frecuente de muerte. La incidencia del hepatocarcinoma varía ampliamente a lo largo de la geografía mundial. Se han descrito tasas de 2 a 50 casos por 100.000 habitantes al año, en correlación a la epidemiología de sus factores de riesgo y la distribución de los diversos genotipos virales. Las zonas más prevalentes son el Sudeste Asiático y el África Subsahariana, donde la infección por el virus de la hepatitis B (VHB) es endémica. Los estudios más recientes objetivan un aumento mundial en la incidencia del CHC, incluyendo los países occidentales, debido a la mayor diseminación del virus de la hepatitis C (VHC) en las décadas de los 60 y 70 además de un aumento en el consumo excesivo de alcohol. La elevada complejidad de esta neoplasia y las patologías con las que se haya íntimamente relacionada, hacen necesario un abordaje multidisciplinar para su manejo, implicando a múltiples especialidades tanto médicas como quirúrgicas

Optimal diagnostic accuracy of quantitative faecal immunochemical test positivity thresholds for colorectal cancer detection in primary health care: a community‐based cohort study

Background Optimizing colonoscopy resources is challenging, and information regarding performing diagnostic quantitative faecal immunochemical test (FIT) in daily clinical practice in primary health care is still limited. This study aimed to assess the sensitivity, specificity, positive predictive value and negative predictive value of varying FIT positivity thresholds on colorectal cancer (CRC) detection in primary health care. Methods A retrospective cohort study of 38,675 asymptomatic and symptomatic patients with a FIT (OC-Sensor™) performed between 2012 and 2016 in a primary health-care setting, using a clinical laboratory database of two Spanish areas linked with the National Health System's Hospital Discharge Records Database. The primary outcome was 2-year CRC incidence. Results The mean age of the participants was 63.2 years; 17,792 (46.0%) were male. CRC prevalence was 1.7% (650/38,675). The percentage of patients with a FIT result above the threshold was 20.7% and 14.6% for 10 μg Hb/g faeces and 20 μg Hb/g faeces thresholds, respectively. Sensitivity was 90.5% (95% confidence interval 88.0%–92.5%) at a 10 μg Hb/g faeces threshold, and this decreased by 3.1% when a 20 μg Hb/g faeces threshold was used. The negative predictive value for CRC was at least 99.2% in any subgroup analysed. At a 20 μg Hb/g faeces threshold, less than one additional CRC would be missed per 1000 patients investigated, while approximately 1.3 times more colonoscopy examinations were needed to identify an incidence of CRC using the lowest threshold for any situation analysed. Conclusions In primary health care, a quantitative FIT threshold should be tailored to colonoscopy capacity and CRC prevalence in specific populations.Instituto de Salud Carlos III, España | Ref. PI17/0083

Optimal diagnostic accuracy of quantitative faecal immunochemical test positivity thresholds for colorectal cancer detection in primary health care: A community-based cohort study

BACKGROUND: Optimizing colonoscopy resources is challenging, and information regarding performing diagnostic quantitative faecal immunochemical test (FIT) in daily clinical practice in primary health care is still limited. This study aimed to assess the sensitivity, specificity, positive predictive value and negative predictive value of varying FIT positivity thresholds on colorectal cancer (CRC) detection in primary health care. METHODS: A retrospective cohort study of 38,675 asymptomatic and symptomatic patients with a FIT (OC‐Sensor™) performed between 2012 and 2016 in a primary health‐care setting, using a clinical laboratory database of two Spanish areas linked with the National Health System's Hospital Discharge Records Database. The primary outcome was 2‐year CRC incidence. RESULTS: The mean age of the participants was 63.2 years; 17,792 (46.0%) were male. CRC prevalence was 1.7% (650/38,675). The percentage of patients with a FIT result above the threshold was 20.7% and 14.6% for 10 μg Hb/g faeces and 20 μg Hb/g faeces thresholds, respectively. Sensitivity was 90.5% (95% confidence interval 88.0%–92.5%) at a 10 μg Hb/g faeces threshold, and this decreased by 3.1% when a 20 μg Hb/g faeces threshold was used. The negative predictive value for CRC was at least 99.2% in any subgroup analysed. At a 20 μg Hb/g faeces threshold, less than one additional CRC would be missed per 1000 patients investigated, while approximately 1.3 times more colonoscopy examinations were needed to identify an incidence of CRC using the lowest threshold for any situation analysed. CONCLUSIONS: In primary health care, a quantitative FIT threshold should be tailored to colonoscopy capacity and CRC prevalence in specific populations

Predictive value of carcinoembryonic antigen in symptomatic patients without colorectal cancer: A post-hoc analysis within the COLONPREDICT cohort

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 ± 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3–3.1), CRC (HR 4.4, 95% CI 1.1–17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0–2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3–5.8), rectal bleeding (OR 0.3, 95% CI 0.1–0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7–7.1). However, CEA was increased only in 31.8% (95% CI, 16.4–52.7%) and 50% (95% CI, 25.4–74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC.Instituto de Salud Carlos III, España | Ref. PI17/0083