Pruebas no invasivas para el tamizaje del cáncer colon: fundamentos básico-clínicos y recientes avances biotecnológicos / Non-invasive tests for colorectal cancer screening: basic-clinical fundamentals and recent biotechnological advances

Colorectal Cancer (CRC) is the third most frequent neoplasia worldwide. Despite the significant advances in surgical techniques and the development of new targeted antineoplastic therapies for this type of tumor, primary prevention and early diagnosis of malignant precursor lesions will continue to be the best strategies to reduce their incidence, morbidity, and mortality. Technologies for CRC screening can be classified into two groups, those of an invasive nature, such as colonoscopy and all its different modalities of use, and those of a non-invasive nature, such as laboratory tests and imaging. This review, will focus exclusively on non-invasive screening tests, excluding imaging. Specifically, it will address those that use depositions as a sample. This review will approach the latest international recommendations, regarding the age at which they should be used, their technical-biological bases, the two main types currently used (biochemical and immunological), and we will put into perspective their advantages and their possible disadvantages. Towards the end of this article, the most recent biotechnological developments in relation to molecular tests based on the study of blood samples, will be discussed. Although these tests are not yet in routine clinical use given their high costs, they are promising for the early detection of CRC.

El cáncer colorrectal (CCR) es la tercera neoplasia más común en todo el mundo. A pesar de los avances significativos en las técnicas quirúrgicas y en el desarrollo de nuevas terapias antineoplásicas para este tipo de tumor, la prevención primaria y el diagnóstico precoz de lesiones precursoras malignas siguen siendo las mejores estrategias para reducir la incidencia, morbilidad y mortalidad asociadas al CCR. Existen dos tipos de tecnologías para el tamizaje del CCR: las invasivas, como la colonoscopia, y las no invasivas, como los ensayos de laboratorio y la imagenología. Esta revisión, se centrará exclusivamente en las pruebas de tamizaje no invasivas que utilizan muestras de deposiciones, excluyendo las imágenes. Se abordarán las últimas recomendaciones internacionales sobre el momento etario en que se deben utilizar, sus bases técnico-biológicas, los dos principales tipos utilizados en la actualidad (bioquímico e inmunológico) y pondremos en perspectiva sus ventajas y posibles desventajas. Al final de esta revisión, se discutirá brevemente los últimos avances biotecnológicos relacionados con pruebas moleculares basadas en el estudio de muestras sanguíneas. Aunque estas pruebas aún no son de uso clínico habitual debido a sus altos costos, representan una prometedora innovación para la detección temprana del CCR.

Indicadores de desempeño de un programa de rastreo de cáncer colorrectal en la provincia del Neuquén, Argentina, 2015-2019 / Performance indicators of a colorectal cancer screening program in the province of Neuquén, Argentina, 2015-2019

INTRODUCCIÓN: El cáncer colorrectal (CCR) es una causa frecuente de mortalidad en adultos. El objetivo de este estudio fue mostrar resultados de la implementación del Programa de Rastreo de Cáncer Colorrectal (PRCCR) en la provincia del Neuquén, Argentina. MÉTODOS: Se realizó un estudio retrospectivo con análisis de resultados de sangre oculta en materia fecal (SOMF) y videocolonoscopía (VCC) en personas de 50-75 años, en efectores del sistema de salud pública en 2015-2019. Se determinó porcentaje de participación, resultados de SOMF, realización de colonoscopía en pacientes con SOMF positiva y sus hallazgos, y valor predictivo positivo (VPP) para detección de lesiones y de CCR. RESULTADOS: Se analizaron 11 189 SOMF. La participación promedio fue 6,52% de la población objetivo. Tuvieron SOMF positiva el 24,6% de los participantes; de ellos, realizaron la VCC un 24%. Se encontró lesión significativa en el 24,8% (pólipos adenomatosos 21,9%, cáncer 2,9%), con un VPP para la detección de lesiones del 34,3%. Tuvieron adenomas avanzados el 7,4%. Repitieron la SOMF tras un resultado negativo (segunda o tercera ronda) el 17,6% de los pacientes, y realizaron una VCC de control tras el hallazgo de un pólipo adenomatoso el 13,7%. DISCUSIÓN: El PRCCR en Neuquén muestra algunos indicadores que deben mejorarse (cobertura, realización de VCC) y otros adecuados (frecuencia de lesiones). Ante las dificultades se pueden plantear medidas más focalizadas, como la aplicación de escalas de riesgo de CCR, rastreo bianual, etc.

INTRODUCTION: Colorectal cancer (CRC) is a leading cause of mortality among adults. The objective of this study was to show results of the implementation of the colorectal cancer screening program (CRCSP) in the province of Neuquén, Argentina. METHODS: A retrospective study was conducted, with analysis of fecal occult blood test (FOBT) results in people aged 50 to 75 years, in public hospitals between 2015- 2019. Participation rate, FOBT results, colonoscopy (CC) performance in patients with positive FOBT and their findings, and positive predictive value (PPV) for detection of lesions and CRC were determined. RESULTS: A total of 11,189 FOBT were requested. The average participation was 6.52% of the target population, 24.6% of the participants had positive FOBT, and 24% of them had a CC performed. A significant lesion was found in 24.8% (adenomatous polyps 21.9%, cancer 2.9%), with a PPV for the detection of lesions of 34.3%. Furthermore, 7.4% had advanced adenomas, 17.6% of the patients repeated the FOBT after a negative result (second or third round), and 13.7% had a control CC performed after the finding of an adenomatous polyp. DISCUSSION: The CRCSP in Neuquén shows some indicators that need to be improved (coverage, conduction of CC) and others that are adequate (frequency of findings). In view of these difficulties, some more focused screening measures can be considered, such as use of CRC risk scales, bi-annual screening, etc.

Test para el diagnóstico precoz de lesiones premalignas de colon / A Test for Early Diagnosis of Premalignant Colonic Lesions

Introducción: El cáncer colorrectal en nuestro país ocupa la tercera causa de muerte por tumores malignos y constituye un problema de salud a nivel mundial, que en la actualidad es prevenible al realizar pruebas para la detección de lesiones premalignas. Objetivo: Evaluar el valor presuntivo de lesiones premalignas colónicas en pacientes con sangre oculta en las heces. Métodos: Se realizó estudio observacional, descriptivo, transversal, en pacientes con sangre oculta en las heces, atendidos en el Servicio de Gastroenterología del Hospital Docente Clínico Quirúrgico Diez de Octubre, a los cuales se les realizó colonoscopia, en el período comprendido de enero de 2016 a enero de 2017. Para evaluar las variables se utilizó el porcentaje como medida matemática y los resultados fueron expuestos en tablas. Resultados: Al finalizar el estudio se observó un predomino del sexo femenino. La pesquisa, el cambio del hábito intestinal y las diarreas crónicas fueron las indicaciones más frecuentes de sangre oculta en heces. Los pólipos y las lesiones de aspecto malignas fueron los diagnósticos colonoscópicos más frecuentes. Las lesiones de aspecto malignas se localizaron en mayor proporción en colon izquierdo. El diagnóstico histológico más frecuente fueron los adenomas y adenocarcinomas. Conclusiones: El test de sangre oculta en heces es un método predictivo en la pesquisa de lesiones premalignas y malignas de colon en pacientes atendidos en el primer nivel de atención(AU)

Introduction: In Cuba, colorectal cancer accounts for the third cause of death by malignant tumors, while it is a worldwide health problem, currently preventable by performing tests for the detection of premalignant lesions. Objective: To evaluate the presumptive value of colonic premalignant lesions in patients with fecal occult blood. Methods: An observational, descriptive and cross-sectional study was carried out in patients with fecal occult blood, who received attention in the gastroenterology service of Diez de Octubre Surgical Clinical Teaching Hospital and underwent colonoscopy, in the period from January 2016 to January 2017. To evaluate the variables, the percentage was used as a mathematical measure and the results were shown in tables. Results: At the end of the study, a predominance of the female sex was observed. Screening, change of bowel habit and chronic diarrhea were the most frequent indications of fecal occult blood. Polyps and malignant lesions were the most frequent colonoscopic diagnoses. Malignant-appearing lesions were mostly located in the left colon. The most frequent histological diagnosis was made up of adenomas and adenocarcinomas. Conclusions: The fecal occult blood test is a predictive method for the detection of premalignant and malignant lesions of the colon in patients who receive attention at the first level of care(AU)

Test de sangre oculta en deposiciones para programas de cribado de cáncer colorrectal: actualización / Fecal occult blood test for colorectal cancer screening

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.

Rastreo de cáncer colorrectal Análisis de resultados en la provincia de Neuquén, Argentina, 2015-2019 / Colorectal cancer screening: analysis of results in the Province of Neuquén, Argentina, 2015-2019

INTRODUCCIÓN: El Programa de Prevención de Tumores de la Provincia del Neuquén recomienda la Sangre Oculta en Materia Fecal Inmunológica (SOMFi) como intervención de rastreo, con posterior confirmación por videocolonoscopía (VCC) en pacientes con resultado positivo. El objetivo del estudio fue conocer los resultados de la utilización de SOMFi, la realización de VCC confirmatoria y sus hallazgos. MÉTODOS: Se realizó un estudio retrospectivo, que analizó los resultados de SOMFi obtenidos en personas de 50 a 75 años en todos los efectores del Sistema de Salud Pública de Neuquén en el período 2015-2019 sobre la base de registros informáticos provinciales y de cada centro de endoscopía. Se determinó la frecuencia de resultados de SOMFi, de VCC en los pacientes con SOMFi positiva y sus hallazgos. RESULTADOS: De 9909 muestras analizadas, 23,1% fueron positivas. Se realizó VCC confirmatoria en 24,1% de los pacientes con SOMFi positiva; presentaron cáncer el 3,7% de los casos, pólipos el 35% y estudio normal el 61,3%. Los tipos histológicos de los pólipos fueron: tubular (49%), hiperplásico (21,3%), tubulovelloso (20%), aserrado (7,2%) y otros tipos (2,5%). DISCUSIÓN: La frecuencia de SOMFi positiva fue mayor a la publicada. Solo el 20% de los pacientes realizó VCC confirmatoria. La frecuencia de cáncer y pólipos encontrados fue similar a la de otros estudios publicados. Debe incrementarse la realización de VCC confirmatoria.(AU)

INTRODUCTION: Neuquén Province Cancer Prevention Program recommends Fecal Immunochemical Test (FIT) as a screening intervention, with subsequent confirmation by video-colonoscopy (VCC) in patients with a positive result. The objective of the study was to know the results of the use of FIT, the performance of confirmatory VCC and its findings. METHODS: A retrospective study was carried out. It analyzed the results of FIT in people aged 50-75 years, considering tests conducted in all agents of the Neuquén Public Health System in 2015- 2019 based on provincial computer records and data from each endoscopy center. The frequency of FIT results, VCC in patients with positive FIT and findings was determined. RESULTS: Of 9909 samples analyzed, 23.1% were positive. Confirmatory VCC was performed in 24.1% of the patients with positive FIT, with 3.7% having cancer, 35% with polyps and 61.3% of normal studies. The histological types of the polyps were tubular (49%), hyperplastic (21.3%), tubulovillous (20%), serrated (7.2%) and other types (2.5%). DISCUSSION: The frequency of positive FIT was higher than published. Only one in five patients with positive FIT underwent confirmatory VCC. The frequency of cancer and polyps was similar to the one found in other published studies. It is necessary to increase the number of confirmatory VCC.AU)

Rastreo de cáncer colorrectal Análisis de resultados en la provincia de Neuquén Argentina, 2015-2019 / Colorectal cancer screening: analysis of results in the Province of Neuquén, Argentina, 2015-2019

INTRODUCCIÓN: El Programa de Prevención de Tumores de la Provincia del Neuquén recomienda la Sangre Oculta en Materia Fecal Inmunológica (SOMFi) como intervención de rastreo, con posterior confirmación por videocolonoscopía (VCC) en pacientes con resultado positivo. El objetivo del estudio fue conocer los resultados de la utilización de SOMFi, la realización de VCC confirmatoria y sus hallazgos. MÉTODOS: Se realizó un estudio retrospectivo, que analizó los resultados de SOMFi obtenidos en personas de 50 a 75 años en todos los efectores del Sistema de Salud Pública de Neuquén en el período 2015-2019 sobre la base de registros informáticos provinciales y de cada centro de endoscopía. Se determinó la frecuencia de resultados de SOMFi, de VCC en los pacientes con SOMFi positiva y sus hallazgos. RESULTADOS: De 9909 muestras analizadas, 23,1% fueron positivas. Se realizó VCC confirmatoria en 24,1% de los pacientes con SOMFi positiva; presentaron cáncer el 3,7% de los casos, pólipos el 35% y estudio normal el 61,3%. Los tipos histológicos de los pólipos fueron: tubular (49%), hiperplásico (21,3%), tubulovelloso (20%), aserrado (7,2%) y otros tipos (2,5%). DISCUSIÓN: La frecuencia de SOMFi positiva fue mayor a la publicada. Solo el 20% de los pacientes realizó VCC confirmatoria. La frecuencia de cáncer y pólipos encontrados fue similar a la de otros estudios publicados. Debe incrementarse la realización de VCC confirmatoria.

Prueba piloto para la implementación del Programa Nacional de Prevención y Detección Temprana de Cáncer Colorrectal en Entre Ríos / Pilot test for the implementation of the National Program for Prevention and Early Detection of Colorectal Cancer in Entre Ríos

INTRODUCCIÓN: El cáncer colorrectal (CCR) es uno de los tumores malignos más frecuentes y representa un problema de salud pública a nivel mundial. En Argentina, con 13 558 casos en 2012 se ubica en segundo lugar después del cáncer de mama y tiene una elevada mortalidad debido al diagnóstico tardío. El objetivo de este estudio fue evaluar la factibilidad organizacional y los resultados a corto plazo de la implementación local del Programa Nacional de Prevención y Detección Temprana de Cáncer Colorrectal (PNCCR). MÉTODOS: Se realizó un estudio descriptivo transversal, que analizó las actividades de una prueba piloto de programa de pesquisa de CCR, efectuado en tres ciudades del departamento La Paz (Entre Ríos) entre febrero de 2019 y febrero de 2020. RESULTADOS: La población objetivo fue de 730 personas (hombres y mujeres de 50 a 64 años), de las cuales 325 (45%) se realizaron test inmunoquímico de sangre oculta en materia fecal (TSOMFi). Se obtuvieron 81 positivos (24,9%), 226 negativos (69,5%) y 18 inadecuados (5,5%). Se articularon 42 videocolonoscopias (VCC), de las cuales fueron realizadas 36, lo que representa un índice de cumplimiento de VCC luego de TSOMFi positivo del 43,2%, con hallazgos endoscópicos en 5 de ellos (14,2%). DISCUSIÓN: La prueba piloto cumplió el objetivo de evaluar la factibilidad organizacional de implementar el PNCCR en la provincia de Entre Ríos, aportando información e identificando problemas para repensar las estrategias sanitarias.

Head-to-head comparison of the test performance of self-administered qualitative vs. laboratory-based quantitative fecal immunochemical tests in detecting colorectal neoplasm / 中华医学杂志(英文版)

BACKGROUND@#Fecal immunochemical tests (FITs) are the most widely used non-invasive tests in colorectal cancer (CRC) screening. However, evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse.@*METHODS@#Based on a CRC screening trial (TARGET-C), we included 3144 pre-colonoscopy fecal samples, including 24 CRCs, 230 advanced adenomas, 622 non-advanced adenomas, and 2268 participants without significant findings at colonoscopy. Three self-administered qualitative FITs (Pupu tube) with positivity thresholds of 8.0, 14.4, or 20.8 μg hemoglobin (Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT (OC-Sensor) with a positivity threshold of 20 μg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory. The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds (for the quantitative FIT).@*RESULTS@#At the thresholds preset by the manufacturers, apart from the qualitative FIT-3, significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1 (33.9% [95% CI: 28.7-39.4%]) and qualitative FIT-2 (22.2% [95% CI: 17.7-27.2%]) compared to the quantitative FIT (11.7% [95% CI: 8.4-15.8%]), while at a cost of significantly lower specificities. However, such difference was not observed for detecting CRC. For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly, there were no significant differences in terms of sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs, which was further evidenced in ROC analysis.@*CONCLUSIONS@#Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer, such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates. Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates.

Métodos de rastreo del cáncer de colon / Colon cancer screening methods

El cáncer colorrectal presenta un problema para la salud pública a nivel mundial. En Argentina, se diagnostican aproximadamente 13.500 casos cada año. El tamizaje como medida de prevención secundaria es una medida beneficiosa para lograr un abordaje temprano con mejores resultados. Los dos métodos más utilizados para el tamizaje son la videocolonoscopía y la prueba de sangre oculta en materia fecal, sobre todo la de tipo inmunoquímico que con el paso de los años fue reemplazando a la prueba de guayaco por su mayor practicidad. El primero es un método invasivo y que requiere anestesia, mientras que el segundo no tiene un efecto adverso directo pero debe realizarse con una cadencia mayor. El objetivo de los autores de este artículo fue evaluar la evidencia sobre la sensibilidad y especificidad de ambos métodos, como también sus beneficios y daños a partir de la consulta de un paciente a su médico de familia. Ninguna prueba parecería ser inferior para el tamizaje de cáncer colorrectal en una población de riesgo promedio, y ambas pueden usarse en programas de rastreo. Sin embargo, no existen estudios que comparen ambos métodos de manera directa, y toda prueba inmunoquímica fecal positiva debe ser seguida de una colonoscopía. La elección de la prueba puede depender de los valores y preferencias de los pacientes. (AU)

Colorectal cancer presents a public health problem worldwide. In Argentina, approximately 13,500 cases appear each year. Screening as a secondary prevention measure is a beneficial measure to achieve an early approach with better results. The two most used methods for screening are video colonoscopy and faecal immunochemical test, the former being invasiveand requiring anaesthesia, while the latter does not have a direct adverse effect but must be performed at a higher rate. The objective of this article was to evaluate the evidence for the sensitivity and specificity of both methods, as well as their benefits and harms. No test would appear to be inferior for colorectal cancer screening in an average-risk population, and both can be used in screening programs. However, there are no studies comparing both methods directly, and any positive faecal immunochemical test should be evaluated with a colonoscopy. The choice of the test may depend on the values and preferences of the patients. (AU)

Estudio prospectivo acerca de la precisión diagnóstica del test inmunológico de sangre oculta en materia fecal en una única ronda para la realización de pesquisa del cáncer colorrectal en pacientes de riesgo promedio en la Argentina / Prospective study on the diagnostic accuracy of the immunochemical fecal occult blood test in a single round for colorectal cancer screening in average risk patients in Argentina

Introducción: El cáncer colorrectal (CCR) es la segunda causa de muerte por cáncer en Argentina. Debido a su alta prevalencia es fundamental normatizar un programa de pesquisa para la prevención y detección temprana. La precisión del test de sangre oculta en materia fecal inmunológico (SOMFi) para pesquisa de CCR en población de riesgo promedio ha demostrado ser adecuada según la bibliografía internacional, no habiendo, sin embargo, información a nivel local. El objetivo es evaluar en nuestro medio la precisión diagnóstica del test de SOMFi en una única ronda para la pesquisa de CCR en pacientes de riesgo promedio. Diseño: Prospectivo de precisión diagnóstica. Material y Método: Se incluyeron pacientes con riesgo promedio que consultaron para realizar una videocolonoscopía (VCC) por pesquisa de CCR en el Hospital Alemán de Buenos Aires, entre el 1 de junio del 2015 y 31 diciembre de 2017. Se excluyeron todos los pacientes con riesgo incrementado para CCR. Todos los pacientes realizaron el test de SOMFi y posteriormente la VCC. Los endoscopistas estaban ciegos para el resultado del test al momento de realizar la VCC. Se evaluó la precisión diagnóstica del test SOMFi para detectar lesiones neoplásicas avanzadas (LNA) calculando la sensibilidad (S), especificidad (E), valor predictivo positivo (VVP) y negativo (VVN), coeficiente de probabilidad positivo (CP+) y negativo (CP-). Se evaluó también la precisión para la detección de adenomas de bajo riesgo, pólipos aserrados y CCR. Resultados: Se incluyeron un total de 300 pacientes; 273 (91%) entregaron la muestra de materia fecal para realizar el test de SOMFi y completaron la VCC. La edad media de los pacientes fue de 56.9 (40-85) años y 54% fueron hombres. Del total de pacientes que realizaron ambos estudios (273), 53 pacientes (19%) presentaron al menos un adenoma de bajo riesgo, en 18 pacientes (6,59%) observamos al menos un adenoma aserrado sésil y en 21 pacientes (7,7%) al menos una lesión neoplásica avanzada (LNA). Solo 4 pacientes (1.5%) presentaron CCR. En cuanto a la precisión diagnóstica del test de SOMFi en una única ronda para detectar LNA observamos una S de 30%, E de 84%, VPP de 13% y un VPN de 94%. Para adenomas de bajo riesgo observamos una S de 13%, E de 84%, VPP de 17%, VPN de 79%. Para adenomas aserrados sésiles observamos una S de 16.7%, E de 87%, VPP de 11% y de VPN 91%. La precisión para el CCR fue la siguiente, S de 75%, E de 83%, VPP 6%, VPN 99%. No se observaron complicaciones post procedimientos. Conclusiones: La precisión diagnóstica del test de SOMFi en nuestro medio es comparable a los resultados internacionales. Sin embargo, la baja precisión observada en una única ronda realza la necesidad de realizarlo de forma anual o bianual para poder optimizar su precisión y lograr programas de pesquisa efectivos.(AU)

Background: Colorectal cancer (CRC) is the second leading cause of cancer death in Argentina. Due to its high prevalence, it is essential to standardize a screening program for prevention and early detection. According to international literature, the accuracy of the immunochemical fecal occult blood test (FIT) for CRC screening in an average-risk population has proven to be adequate, but there is no information at the local level. Objective: To evaluate the diagnostic accuracy of the FIT test in a single round for CRC screening in average-risk patients in our setting. Design: Diagnostic accuracy prospective study. Material and Methods: Average-risk patients who consulted for a CRC screening video colonoscopy (VCC) at the Hospital Alemán of Buenos Aires, between June 1, 2015 and December 31, 2017 were included. All patients with increased risk for CRC were excluded. All patients performed FIT and subsequently VCC. The endoscopists were blind to FIT result at the time of VCC. The diagnostic accuracy of FIT to detect advanced neoplastic lesions (ANL) was evaluated by calculating sensitivity (S), specificity (Sp), positive predictive value (PPV), negative (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-). The accuracy for the detection of low-risk adenomas, serrated polyps and CRC was also evaluated. Results: A total of 300 patients were included; 273 (91%) submitted the stool sample to perform FIT and completed VCC. The mean age of patients was 56.9 (40-85) years and 54% were men. Of the total number of patients who carried out both studies (273), 53 (19%) patients had at least one low-risk adenoma, 18 (6.59%) patients had at least one sessile serrated adenoma and 21 (7.7%) patients had at least one ANL. Only 4 (1.5%) patients presented CRC. The diagnostic accuracy of FIT in a single round to detect ANL was: S 30%, Sp 84%, PPV 13%, NPV 94%; for low-risk adenomas: S 13%, Sp 84%, PPV 17%, NPV 79%; for sessile serrated adenomas: S 16.7%, Sp 87%, PPV 11%, NPV 91% and for CRC: S 75%, Sp 83%, PPV 6%, NPV 99%. No post-procedure complications were observed. Conclusions: The diagnostic accuracy of FIT in our setting is comparable to international results. However, the low precision observed in a single round highlights the need to do it annually or biannually in order to optimize its accuracy and achieve effective screening programs. (AU)

Acurácia diagnóstica de teste quantitativo imunoquímico fecal com uma amostra ou com duas amostras para detectar neoplasia intestinal / Diagnostic accuracy of one sample or two samples quantitative fecal immunochemical tests for intestinal neoplasia detection

ABSTRACT BACKGROUND: Rectal bleeding is the most important symptom of intestinal neoplasia; thus, tests of occult blood detection in stools are widely used for pre neoplastic lesions and colorectal cancer (CRC) screening. OBJECTIVE: Evaluate the accuracy of OC-Sensor quantitative test (Eiken Chemical, Tokyo, Japan) at cut-off 10 µg Hb/g feces (50 ng/mL) in a cohort of subjects that had to undergo diagnostic colonoscopy, and if more than one sample collected in consecutive days would improve the diagnostic accuracy of the test. METHODS: Patients (mean age 56.3±9.7 years) that underwent colonoscopy prospectively randomly received one (1-sample FIT, FIT 1) or two (2-sample FIT, FIT 2) collection tubes. They collected the stool sample before starting colonoscopy preparation. Samples were analyzed by the OC-Auto Micro 80 (Eiken Chemical, Tokyo, Japan). The performance of FIT 1 and FIT 2 were compared to the colonoscopy findings. RESULTS: Among 289 patients, CRC was diagnosed in 14 (4.8%), advanced adenoma in 37 (12.8%), early adenoma in 71 (24.6%) and no abnormalities in 141 (48.8%). For FIT 1, the sensitivity for CRC was 83.3% (95%CI 36.5-99.1%), for advanced adenoma was 24% (95%CI 10.1-45.5%), with specificity of 86.9% (95%CI 77.3-92.9%). For FIT 2, the sensitivity for CRC was 75% (95%CI 35.6-95.5%), for advanced adenoma was 50% (95%CI 22.3-77.7%), with specificity of 92.9% (95%CI 82.2-97.7%). The positive likelihood ratios were 1.8 (95%CI 0.7-4.4 for FIT 1) and 7.1 (95%CI 2.4-21.4 for FIT 2) for advanced adenoma, and 6.4 (95%CI 3.3-12.3, for FIT 1) and 10.7 (95%CI 3.8-29.8, for FIT 2) for CRC. The negative likelihood ratio were 0.9 (95%CI 0.7-1, for FIT 1) and 0.5 (95%CI 0.3-0.9, for FIT 2) for advanced adenoma, and 0.2 (0.03-1.1, for FIT 1) and 0.3 (0.08-0.9, for FIT 2) for CRC. The differences between FIT 1 and FIT 2 performances were not significant. However, the comparison of the levels of hemoglobin in feces of patients of FIT 1 and FIT 2 showed that the differences between no polyp group and advanced adenoma and CRC were significant. CONCLUSION: The accuracy of OCR Sensor with 10 µg Hb/g feces cut-off was comparable to other reports and two-sample collection improved the detection rate of advanced adenoma, a pre neoplastic condition to prevent CRC incidence.

RESUMO CONTEXTO: Sangramento retal é o sintoma mais importante de neoplasia intestinal; portanto, testes para detecção de sangue oculto nas fezes são amplamente usados para rastreamento de lesões pré-neoplásicas e de câncer colorretal (CCR). OBJETIVO: Avaliar a acurácia do teste quantitativo OC-Sensor (Eiken Chemical, Tokyo, Japan) com o valor de corte de 10 µg Hb/g fezes (50 ng/mL) numa coorte de indivíduos que se submeteram à colonoscopia diagnóstica, e se mais de uma amostra coletada em dias consecutivos melhoraria a acurácia diagnóstica do teste. MÉTODOS: Pacientes (idade média 56,3±9,7 anos) que se submeteram à colonoscopia prospectivamente, randomicamente, receberam tubos de coleta: um (1-amostra FIT, FIT 1), ou dois (2-amostra FIT, FIT 2). Eles coletaram as amostras de fezes antes de iniciar o preparo da colonoscopia. As amostras foram analisadas pelo OC-Auto Micro 80 (Eiken Chemical, Tokyo, Japan). As performances do FIT 1 e do FIT 2 foram comparadas com os achados da colonoscopia. RESULTADOS: Entre 289 pacientes, CCR foi diagnosticado em 14 (4,8%), adenoma avançado em 37 (12,8%), adenoma precoce em 71 (24,6%) e sem anormalidades em 141 (48,8%). Para FIT 1, a sensibilidade para CCR foi 83,3% (95%IC 36,5-99,1%), para adenoma avançado foi 24% (95%IC 10,1-45,5%), com especificidade de 86,9% (95%IC 77,3-92,9%). Para FIT 2, a sensibilidade para CCR foi 75% (95%IC 35,6-95,5%), para adenoma avançado foi 50% (95%IC 22,3-77,7%), com especificidade de 92,9% (95%IC 82,2-97,7%). A razão de verossimilhança positiva foi 1,8 (95%IC 0,7-4,4 para FIT 1) e 7,1 (95%IC 2,4-21,4 para FIT 2) para adenoma avançado, e 6,4 (95%IC 3,3-12,3, para FIT 1) e 10,7 (95%IC 3,8-29,8, para FIT 2) para CCR. A razão de verossimilhança negativa foi 0,9 (95%IC 0,7-1, para FIT 1) e 0,5 (95%IC 0,3-0,9, para FIT 2) para adenoma avançado, e 0,2 (0,03-1,1, para FIT 1) e 0,3 (0,08-0,9, para FIT 2) para CCR. As diferenças de performance entre FIT 1 e FIT 2 não foram significantes. Entretanto, a comparação dos níveis de hemoglobina nas fezes dos pacientes de FIT 1 e FIT 2 mostraram que as diferenças entre sem pólipo e adenoma avançado e CCR foram significantes. CONCLUSÃO: A acurácia do OCR Sensor com valor de corte de 10 µg Hb/g de fezes foi comparável a outras publicações e a coleta de duas amostras melhorou a taxa de detecção de adenoma avançado, lesão pré-neoplásica, para prevenir CCR.

Investigación traslacional en microbioma (InTraMic): un área de interés común y creciente en el IMTIB, Hospital Italiano e Instituto Universitario / Translational research in microbiome (InTraMic): an area of common and growing interest at IMTIB, Hospital Italiano and Instituto Universitario

Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso. (AU)

It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother's skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project "Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents". At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research. (AU)

Comportamiento del cáncer colorrectal diagnosticado por colonoscopia en el Hospital Militar "Mario Muñoz Monroy". Matanzas / Behavior of the colorectal cancer diagnosed by colonoscopy in the hospital military "Mario Muñoz Monroy". Matanzas

RESUMEN Introducción: el cáncer colorrectal constituye un serio problema de salud por su alta incidencia. Es una entidad que afecta significativamente a la humanidad y conlleva a una alta mortalidad. Objetivo: determinar el comportamiento de los pacientes con cáncer colorrectal diagnosticado por colonoscopia en el Hospital Militar "Mario Muñoz", Matanzas. Materiales y Métodos: se realizó un estudio observacional, descriptivo y prospectivo en pacientes con sangre oculta en heces fecales y diagnóstico colonoscópico de cáncer colorrectal, desde enero del 2015 a noviembre del 2018. El universo quedó conformado por 135 pacientes que cumplieron con los criterios de selección. Se estudiaron variables como: grupo etario, sexo, factores de riesgo, síntomas y signos, localización y estadio. Se utilizó una planilla de recolección de datos. Se emplearon métodos de estadística descriptiva y los resultados fueron presentados en tablas. Resultados: en 722 colonoscopias realizadas a pacientes con sangre oculta positiva, en el 18.7 % se diagnosticó cáncer colorrectal. Predominó el grupo etario de 61-70 años con un 30.4 % de los pacientes y el sexo masculino (41.4%). Los factores de riesgos más frecuentes) fueron: dieta inadecuada (46.6%), sedentarismo (25.2%) y enfermedad inflamatoria intestinal (29.6%). Los síntomas más frecuentes fueron: diarrea (45.9%), dolor abdominal (31.1%) y dispepsia (25.2%). La localización que predominó fue el recto (24.4%), seguido del colon ascendente (22.2%). Predominaron los pacientes en un estadio II con 42.2%. Conclusiones: el cáncer colorrectal se presentó con mayor frecuencia en pacientes de la 6ta década de vida tal como se reporta en la literatura, asociado a malos hábitos dietéticos e inadecuado modo y estilo de vida que pueden ser modificados a través de estrategias educativas que garanticen la salud de la población (AU).

SUMMARY Introduction: Colorectal cancer [cancer colorectal (CCR) in Spanish] is a serious health problem due to its high incidence. It is an entity affecting the human kind and producing a high mortality. Objective: to determine the behavior of the colorectal cancer diagnosed by colonoscopy in the Military Hospital "Mario Muñoz", Matanzas. Material and methods: a prospective, descriptive, observational study was carried out in patients with hidden blood in fecal feces and colonoscopic diagnosis of colorectal cancer from January 2015 to November 2018. The universe was formed by 135 patients who fulfilled the selection criteria. The studied variables were age group, gender, risk factors, symptoms, locations and stage. A form was used for collecting data. Methods of descriptive statistics were used and the results are showed in charts. Results: In 722 colonoscopies carried out to patients with positive hidden blood, 18.7 % was diagnosed as colorectal cancer. The 61-70 years-old age group (30.4 %) and male gender (41.4 %) predominated. The most frequent risk factors were improper diet (46.6 %), sedentary life style (25.2 %), and inflammatory intestinal disease (29.6 %). The most frequent symptoms were diarrhea (45.9 %), abdominal pain (31.1 %) and dyspepsia (25.2 %). The predominant location was the rectum (24.4 %), followed by ascending colon (22.2 %). Stage II patients predominated, with 42.2 %. Conclusions: colorectal cancer appeared more frequently in patients in their sixth decade of life as it is reported in the literature, associated to bad dietary habits and to an inadequate style and way of life that could be modified through educative strategies warranting the population's health (AU).

Association of fecal occult blood tests results with colonoscopic findings in a general hospital and validation of the screening test / Achados colonoscópicos em pacientes submetidos a exame de sangue oculto nas fezes e validacão deste teste de triagem

ABSTRACT Globally, colorectal cancer is the third leading cause of cancer death among men and the second among women, corresponding to about 10% of all cancers. The Brazilian Ministry of Health and National Cancer Institute recommend the screening of colorectal cancer for people over 50 years-old with Fecal Occult Blood Test. Endoscopy is limited to patients with positive screening results. The aim of this study is to evaluate the incidence of malignant or premalignant lesions diagnosed by endoscopy in patients with positive or negative Fecal Occult Blood Test and assess the efficacy of Fecal Occult Blood Test to predict the finding of a malignant colorectal lesion. We carried out a cross-sectional study among patients with a Fecal Occult Blood Test result that were submitted to colonoscopy, in the same hospital, from March 2016 to July 2017. Sensitivity, specificity, positive and negative predictive value of Fecal Occult Blood Test compared to colonoscopy neoplastic findings was calculated. The total of 92 patients were enrolled, 52 (56.5%) were female, Fecal Occult Blood Test was positive in 42.4% of them and in 41 (44.6%) the colonoscopy showed abnormal findings. Polyps were the most frequent alteration, found in 20 patients (21.7%). Among the patients with polyps, 15 (16.3%) had neoplastic and 5 (5.4%) presented non-neoplastic polyps. The Fecal Occult Blood Test sensitivity for detection of neoplastic polyps was 66.7%, specificity 62.3%, positive predictive value 11% and negative predictive value was 94.2%. Considering the need for a screening method, Fecal Occult Blood Test showed to be an effective and reliable screening test that can be applied in public health programs to detect and prevent colorectal cancer.

RESUMO Globalmente, o carcinoma colorretal é a terceira principal causa de morte por neoplasia entre homens e a segunda entre mulheres, correspondendo a 10% de todas as neoplasias. O Ministério da Saúde Brasileiro e o Instituto Nacional do Câncer recomendam a triagem do câncer colorretal para indivíduos acima de 50 anos, utilizando a Pesquisa de Sangue Oculto nas fezes. A endoscopia é reservada para aqueles com Pesquisa de Sangue Oculto nas fezes positiva. O objetivo deste estudo é avaliar a incidência de lesões malignas/pré-malignas diagnósticas na colonoscopia e correlacionar com os resultados prévios da Pesquisa de Sangue Oculto e verificar a eficácia da Pesquisa de Sangue Oculto para predizer uma lesão colorretal maligna. Realizamos um estudo transversal em pacientes que apresentavam resultados positivos ou negativos de Pesquisa de Sangue Oculto nas fezes e foram submetidos à colonoscopia, na mesma instituição, entre março de 2016 e julho de 2017. Dos 92 participantes; 52 (56,5%) eram do sexo feminino, a Pesquisa de Sangue Oculto nas fezes foi positiva em 42,4%; e em 41 (44,6%) a colonoscopia mostrou alterações. Em 20 pacientes (21,7%) havia pólipos; 15 (16,3%) eram neoplásicos e 5 (5,4%) não neoplásicos. A sensibilidade da Pesquisa de Sangue Oculto nas fezes para detecção de pólipos neoplásicos foi 66,7%; a especificidade 62,3%; o valor preditivo positivo 11% e o valor preditivo negativo 94,2%. Considerando a necessidade de um método de triagem, a Pesquisa de Sangue Oculto nas fezes mostrou ser um exame de triagem eficaz e confiável para ser aplicado em programas de saúde pública com o objetivo de detectar e prevenir o carcinoma colorretal.

Annual Report of the Korean Association of External Quality Assessment Service on Urinalysis and Fecal Occult Blood Testing (2018) / 임상검사와정도관리

In 2018, external quality assessment trials for urinalysis and fecal occult blood (FOB) were performed using 1,590 participants. Urine chemistry tests were performed thrice while urine sediment and FOB tests twice. Urine chemistry tests comprised of pH, protein, glucose, ketone body, bilirubin, blood, urobilinogen, nitrite, leukocyte, and specific gravity analyses. The results of urine chemistry and specific gravity tests showed accuracy rates >95%, except for the pH test. The accuracy rate of urine sediments was low, especially for atypical calcium oxalate crystal and red blood cell cast. In the FOB quality test, reagents showed accuracy rates >90%, except for SD and GC Genedia FOB reagents. In the FOB quantitative test, Alfresa NS-Plus C instrument showed falsely high values in the FOB negative specimens.

Performance Evaluation of SENTiFIT 270 and FOB Gold Reagent for Detecting Fecal Occult Blood / 대한임상미생물학회지

BACKGROUND: Fecal occult blood tests have been widely used to screen for colorectal cancer. SENTiFIT 270 (Sentinel diagnostics, Italy) is a fecal occult blood test with an immunochemical method that utilizes FOB Gold reagents. We evaluated the performance of SENTiFIT 270 using the FOB Gold reagent. In addition, FOB Gold was evaluated with the HITACHI 7180 (Hitachi Ltd., Japan). METHODS: The precision and linearity of the SENTiFIT 270 was evaluated in accordance with applicable Clinical and Laboratory Standard Institute guidelines. The comparison study between SENTiFIT 270-FOB Gold and the OC-Sensor (Eiken chemical Co., Japan) was performed using stool specimens. RESULTS: In the precision evaluation, the total precision of SENTiFIT 270-FOB Gold was 4.94% and 2.54% at high and low concentrations, respectively. The HITACHI 7180-FOB Gold had excellent precision of 4.60% and 2.09% at high and low concentrations, respectively. Linearity was also excellent for the SENTiFIT 270-FOB Gold and HITACHI 7180-FOB Gold at 0.9987 and 0.9986, respectively. The SENTITIF 270-FOB Gold showed excellent agreement with a kappa value of 0.830 and a concordance rate of 93.6%. The HITACHI 7180-FOB Gold showed high agreement with a kappa value of 0.832 and a concordance rate of 93.9%. CONCLUSION: The SENTiFIT 270-FOB Gold showed excellent performance in accuracy, linearity, and comparative inspection ability.