Clinical profile of early- and late-onset colorectal cancer patients in a referral medical center in Medellín, Colombia: A comparative analysis / Perfil clínico de pacientes con cáncer colorrectal de aparición temprana y tardía en un centro médico de referencia en Medellín, Colombia: Un análisis comparativo

Introduction. Incidence of early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) in individuals aged < 50 years, is rising worldwide. Despite the increasing international scientific production on EOCRC, research is limited in Colombia. The objective of this study was to characterize the clinical features of adults with EOCRC and late-onset CRC (LOCRC, CRC in individuals aged ≥ 50 years). Methods. An observational, retrospective, cross-sectional study was conducted with CRC patients ≥ 18 years old at one medical center in Medellín, Colombia. Clinical and pathological data were retrieved from the Institutional Cancer Registry. Two analysis groups were established: EOCRC and LOCRC. The Chi-Square test was applied to compare the variables of interest between both groups. Results. The sample included 1,202 patients, 53.5% were female (N=643) and the median age was 65 years (interquartile range: 55-73). EOCRC represented 15.9% (N=192). LOCRC tended to have more history of cardiometabolic diseases and smoking (p<0.001) than EOCRC. CRC family history was proportionally more frequent in EOCRC (7.3% vs 3.8%; p=0.028) than in LOCRC. Right-sided tumors were more common in LOCRC (30.4% vs 21.9%; p=0.041) and left-sided tumors in EOCRC (30.7% vs 23.2%; p=0.041). Only one patient had inflammatory bowel disease history. Conclusion. EOCRC is clinically distinct from LOCRC regarding pathological and toxicological history as well as tumor location. Our findings provide valuable insights for enhancing clinical decision-making, particularly in relation to age at onset in Colombian CRC patients.

Introducción. La incidencia de cáncer colorrectal (CCR) de aparición temprana (CCR-ATem), definido como CCR en individuos menores de 50 años, está aumentando en todo el mundo. A pesar del incremento en la producción científica internacional sobre CCR-ATem, la investigación es limitada en Colombia. El objetivo de este estudio fue caracterizar clínicamente los adultos con CCR-ATem y CCR de aparición tardía (CCR-ATar, CCR en individuos ≥ 50 años). Métodos. Estudio observacional, retrospectivo, transversal, en el que se incluyeron los pacientes adultos con CCR atendidos en un centro médico de Medellín, Colombia. Los datos se obtuvieron del Registro Institucional de Cáncer. Se establecieron dos grupos de análisis: CCR-ATem y CCR-ATar. Se aplicó la prueba de Chi cuadrado para comparar las variables de interés entre ambos grupos. Resultados. La muestra incluyó 1.202 pacientes, 53,5 % fueron mujeres (N=643), y la mediana de edad fue de 65 años (rango intercuartil: 55-73). CCR-ATem representó el 15,9 % (N=192). CCR-ATar tuvo más casos de enfermedades cardiometabólicas y tabaquismo (p<0,001). El antecedente familiar de CCR fue proporcionalmente más frecuente en CCR-ATem (7,3 % vs. 3,8 %; p=0,028). Los tumores del colon derecho fueron más frecuentes en CCR-ATar (30,4 % vs. 21,9 %; p=0,041) y los del colon izquierdo en CCR-ATem (30,7 % vs. 23,2 %; p=0,041). Solo un paciente tuvo antecedente de enfermedad inflamatoria intestinal. Conclusión. CCR-ATem es clínicamente distinto de CCR-ATar con respecto a antecedentes patológicos y toxicológicos, y localización tumoral. Nuestros hallazgos proporcionan información útil para mejorar la toma de decisiones clínicas, particularmente en relación con la edad de inicio en pacientes colombianos con CCR.

Phytochemicals and colorectal cancer: about polyphenols / Fitoquímicos y cáncer colorrectal: acerca de los polifenoles

Dietary consumption of polyphenols, found in fruits and vegetables, has been associated with a potentially protective role in colorectal cancer (CRC). To establish the state of knowledge regarding advances in polyphenols, CCR and action mechanisms a systematic review and an analysis of information available until 2021 were made. Results indicate that only some polyphenols have in vitro, preclinical and clinical studies. These studies showed that polyphenols will inhibit human CRC cell invasion, migration, metastasis formation, tumor growth. Action mechanisms involve signaling pathways that modulate genes, proteins, markers or cell death inductors, like the AMPK pathway, caspases, Bcl-2, p-Akt, and NF-kB, lysosomal and mitochondrial dysfunction, cellular cycle arrest, among the best known and implied in CRC. Overall, in vitro, preclinical and clinical data on phytochemicals against CRC are still not sufficient and therefore the preventive or therapeutic impacts of dietary phytochemicals on CRC development deserve further research.

El consumo dietético de polifenoles, que se encuentran en frutas y verduras, se ha asociado con un papel potencialmente protector contra el cáncer colorrectal (CCR). Para establecer el estado del conocimiento respecto a los avances en polifenoles, CCR y mecanismos de acción, se realizó una revisión sistemática y un análisis de la información disponible hasta el año 2021. Los resultados indican que sólo algunos polifenoles cuentan con estudios in vitro, preclínicos y clínicos. Estos estudios demostraron que los polifenoles inhiben la invasión, migración, formación de metástasis y crecimiento de tumores de células de CCR humanas. Los mecanismos de acción involucran vías de señalización que modulan genes, proteínas, marcadores o inductores de muerte celular, como la vía AMPK, caspasas, Bcl-2, p-Akt y NF-kB, disfunción lisosomal y mitocondrial, parada del ciclo celular, entre los más conocidos e implicados en el CCR. En general, los datos in vitro, preclínicos y clínicos sobre fitoquímicos contra el CCR aún no son suficientes y, por lo tanto, los impactos preventivos o terapéuticos de los fitoquímicos dietéticos en el desarrollo del CCR requieren más investigación.

Efecto de la implementación de las recomendaciones del protocolo de recuperación mejorada después de cirugía (ERAS) en cirugía colorrectal en un hospital de referencia del suroccidente colombiano / Effect of the implementation of Enhanced Recovery After Surgery (ERAS) protocol recommendations in colorectal surgery at a reference hospital in Southwestern Colombia

Introducción. La implementación del protocolo de recuperación mejorada después de cirugía (ERAS) ha demostrado mejorar los desenlaces en cirugía colorrectal. En Colombia su implementación es escasa y se tiene poca evidencia de sus beneficios. Por esa razón, el objetivo de este estudio fue evaluar el efecto de la implementación del protocolo ERAS en los pacientes sometidos a cirugía colorrectal en un hospital de referencia en el suroccidente colombiano. Métodos. Estudio observacional con abordaje de emulación de experimento clínico ideal. Se incluyeron pacientes adultos sometidos a cirugía colorrectal mayor entre los años 2021 y 2023. Se midió días de estancia hospitalaria, ingreso a unidad de cuidado intensivo (UCI) y la presencia de complicaciones globales, reintervenciones o reingreso hospitalario a 30 días. Se realizó un análisis univariado y multivariado para medir el efecto de la implementación del protocolo ERAS en los desenlaces. Resultados. En total,132 pacientes cumplieron los criterios de inclusión, 79 pacientes en el período previo a la implementación de ERAS y 53 pacientes con el protocolo ERAS. En el análisis multivariado, se encontró una reducción relativa del 77 % para ingreso a UCI, del 57 % de complicaciones globales, del 67 % en el reingreso hospitalario y del 92 % para reintervenciones quirúrgicas tras el alta en los pacientes ERAS. Conclusiones. La implementación de las recomendaciones ERAS en nuestra institución demostró mejorar los resultados clínicos en pacientes sometidos a cirugía colorrectal mayor. En Colombia, se necesita de estudios multicéntricos que permitan evidenciar la plausibilidad y beneficios de estas recomendaciones en otras instituciones.

Introduction. Implementation of the Enhanced Recovery After Surgery (ERAS) protocol has been shown to improve outcomes in colorectal surgery. In Colombia, its implementation is scarce and there is limited evidence of its benefits. For this reason, the objective of this study was to evaluate the effect of ERAS protocol implementation in patients undergoing colorectal surgery in a reference hospital in Southwestern Colombia. Methods. Observational study with ideal clinical experiment emulation approach. Adult patients undergoing major colorectal surgery between 2021 and 2023 were included. Days of hospital stay, admission to the intensive care unit (ICU), and the presence of overall complications, reinterventions, or hospital readmission within 30 days were measured. A univariate and multivariate analysis was performed to measure the effect of the implementation of the ERAS protocol on the outcomes. Results. A total of 132 patients met the inclusion criteria, 79 patients in the period prior to ERAS implementation and 53 patients with the ERAS protocol. In the multivariate analysis, a relative reduction of 77% for ICU admissions, 57% for overall complications, 67% for hospital readmission, and 92% for surgical reinterventions after discharge in ERAS patients was found. Conclusions. Implementation of ERAS recommendations at our institution was shown to improve clinical outcomes in patients undergoing major colorectal surgery, In Colombia, multicenter studies are needed to demonstrate the plausibility and benefits of these recommendations in other institutions.

Fatores associados ao estadiamento do câncer colorretal no estado do Maranhão, Brasil / Factors associated with colorectal cancer staging in the state of Maranhão, Brazil / Factores asociados a la estadificación del cáncer colorrectal en el estado de Maranhão, Brasil

O câncer colorretal é desafiador devido à necessidade de atenção especializada nos serviços de saúde. Assim, objetivou-se analisar os fatores associados ao estadiamento do câncer colorretal (CCR) no estado do Maranhão, no Brasil. Trata-se de um estudo transversal, com abordagem quantitativa. Os dados foram coletados a partir do Sistema de Informação de Registro Hospitalar de Câncer, com a subsequente utilização do teste de qui-quadrado, considerando o nível de significância (p<0,05). Dos 421 casos de CCR analisados, houve predomínio de mulheres (57,8%), acima dos 60 anos (31,3%), de cor parda (68,2%), baixa escolaridade (43%) e múltiplas profissões. O adenocarcinoma foi o mais recorrente dos casos (73,5%) e, após tratamento com cirurgia e quimioterapia, houve remissão da doença em 27,2% e 37,9% dos casos, respectivamente. Houve associação do estadiamento tardio com tipo histológico adenocarcinoma (p<0,001), e os tratamentos recebidos nos casos tardios foram associados à cirurgia e quimioterapia (p<0,001). Os pacientes de casos precoces tiveram maiores possibilidades da remissão completa (p<0,000), sendo o tempo para o tratamento maior que 60 dias em casos tardios. As variáveis analisadas refletem principalmente a demora do diagnóstico, resultando na necessidade de tratamentos conjugados para efetiva possibilidade do desaparecimento da doença. Os casos analisados tiveram estadiamento tardio, o que reflete casos com diagnóstico e tratamento tardio, devido ao caráter silencioso da doença, à dificuldade de acesso dos pacientes aos serviços de saúde e à ainda recente estruturação dos fluxos de atendimento, medida que visa a reduzir a espera, identificar os casos precoces e favorecer melhores condições de tratamento para remissão da doença na população alvo.

Colorectal cancer is a challenge due to the need for specialized care in health services. Thus we aimed to analyze factors associated with colorectal cancer (CRC) staging in the state of Maranhão, Brazil. This is a cross-sectional study, with a quantitative approach. Data were collected from System Information of Hospital Cancer Registry, with subsequent use of the chi-square test, considering the significance level (p<0.05). Of the 421 cases of CRC analyzed, there was a predominance of women (57.8%), over 60 years (31.3%), mixed race (68.2%), low education (43%), and multiple professions. Adenocarcinoma was the most frequent case (73.5%) and, after treatment were treated with surgery and chemotherapy 27.2% and 37.9% of cases showed disease remission, respectively. There was an association between late staging and histological type of adenocarcinoma (p<0.001), and the treatments received in late cases were associated with surgery and chemotherapy (p<0.001). The patients with early cases had greater chances of complete remission (p<0.000), and the time to treatment was greater than 60 days in late cases. The analyzed variables mainly reflect the delay in diagnosis, requiring combined treatments for the effective possibility of healing the disease. The analyzed cases had late staging, which reflects in cases with late diagnosis and treatment, due to the silent nature of the disease, the difficulty of the patient's access to health services, and the recent structuring of service flow, a measure that aims to reduce waiting times, identify early cases and favor better treatment conditions for disease remission in the target population.

El cáncer colorrectal es un reto por la necesidad de atención especializada en los servicios sanitarios. Este trabajo buscó analizar los factores asociados con la estadificación del cáncer colorrectal (CCR) en el estado de Maranhão, Brasil. Se trata de un estudio transversal con enfoque cuantitativo. Los datos se recolectaron del Sistema de Información de Registro Hospitalario de Cáncer, en el que se utilizó la prueba de chi-cuadrado y el nivel de significancia (p<0,05). De los 421 casos de CCR evaluados, hubo predominio de mujeres (57,8%), mayores de 60 años (31,3%), de color pardo (68,2%), bajo nivel educativo (43%) y de múltiples profesiones. El adenocarcinoma fue el más común entre los casos (73,5%) y, tras el tratamiento con cirugía y quimioterapia, se produjo una remisión de la enfermedad en el 27,2% y el 37,9% de los casos. Hubo asociación entre la estadificación tardía con adenocarcinoma de tipo histológico (p<0,001), y los tratamientos que recibieron los casos tardíos se asociaron con cirugía y quimioterapia (p<0,001). Los pacientes con casos tempranos tuvieron mayores posibilidades de remisión completa (p<0,000), y el tiempo hasta el tratamiento fue superior a 60 días en los casos tardíos. Las variables analizadas reflejan principalmente el retraso en el diagnóstico, requiriendo tratamientos combinados para la posibilidad efectiva de desaparición de la enfermedad. Los casos analizados tuvieron estadificación tardía, lo que refleja casos con diagnóstico y tratamiento tardío debido al carácter silencioso de la enfermedad, el acceso de los pacientes a los servicios de salud y la reciente estructuración de los flujos de atención que apuntan a reducir la espera, identificar casos tempranos y favorecer un mejor tratamiento para la remisión de la enfermedad en la población objetivo.

Calidad asistencial y seguimiento de los pacientes operados por cáncer colorrectal en un Hospital de Paysandú, Uruguay / Quality of care and follow-up of patients operated on forcolorectal cancer at the Paysandú Hospital, Uruguay

Introducción: el cáncer colorrectal (CCR) es la segunda causa de muerte dentro de las enfermedades neoplásicas. El pronóstico individual está signado por el estadio de la enfermedad al momento del diagnóstico y la posibilidad de realizar un tratamiento curativo. Este también depende de la estratificación post quirúrgica y de la aparición de complicaciones ulteriores. El objetivo del seguimiento es diagnosticar la recidiva en un estadio potencialmente curable y detectar otros cánceres primarios. Objetivo: realizar una valoración de la calidad de la cirugía colorrectal y el seguimiento de los pacientes operados de CCR en nuestro hospital. Diseño: estudio descriptivo, observacional, retrospectivo. Material y métodos: se analizaron todos los pacientes con CCR operados en el servicio de cirugía del Hospital de Paysandú entre enero de 2017 y diciembre de 2020. Se describen diversas variables que influyen en la calidad quirúrgica y se analizan las relacionadas al seguimiento post operatorio dividiendo a los pacientes en 3 grupos, seguimiento completo, perdidos y sin datos de seguimiento. Resultados: se incluyeron 39 pacientes, con una edad media de 68 años. El 28% se diagnosticaron en estadio IV, con porcentajes bajos en estadios tempranos. Hubo 57% de cirugías de urgencia y 43% electivas. La causa más frecuente de urgencia fue la oclusión intestinal (36,6%). La tasa de dehiscencia anastomótica fue 16,6% y la de mortalidad 15,3%. Solo el 33% de los pacientes tuvieron seguimiento completo. Conclusión: existe un déficit en la atención y el seguimiento de los pacientes operados por CCR en nuestro hospital. Se impone la creación de un equipo específico en el área de coloproctología, así como un protocolo de seguimiento unificado para mejorar estos resultados. (AU)

Introduction: colorectal cancer (CRC) is the second cause of death among neoplastic diseases. The individual prognosis is determined by the stage of the disease at the time of diagnosis and the possibility of curative treatment. This also depends on the postsurgical stratification and the appearance of subsequent complications. The goal of follow-up is to diagnose recurrence at a potentially curable stage and detect other primary cancers. Objective: to carry out an evaluation of the quality of colorectal surgery and the follow-up of patients operated on for CRC in our hospital. Design: descriptive, retrospective observational study. Material and methods: all patients with CRC operated on in the surgery service of the Paysandú Hospital between January 2017 and December 2020 were analyzed. Variables that influence surgical quality are described and those related to postoperative follow-up are analyzed by dividing patients in 3 groups, complete follow-up, lost to follow-up and without follow-up data. Results: Thirty-nine patients were included, with a mean age of 68 years. Twenty-eight percent were diagnosed in stage IV, with low percentages in early stages. There were 57% emergency procedures and 43% elective proceduress. The most common cause of emergency was intestinal obstruction (36.6%). The anastomotic dehiscence rate was 16.6% and the mortality rate was 15.3%. Only 33% of patients had complete follow-up. Conclusion: there is a deficit in the care and follow-up of patients undergoing CRC surgery in our hospital. The creation of a specific team in the area of coloproctology is required, as well as a unified monitoring protocol to improve these results. (AU)

Modulación por Passiflora edulis de triglicéridos y colesterol intracelulares en líneas celulares de cáncer colorrectal SW480 y sus derivadas metastásicas (SW620) / Modulation by Passiflora edulis of intracellular triglycerides and cholesterol in SW480 col orectal cancer cell lines and their metastatic derivatives (SW620)

Cancer cells modify lipid metabolism to proliferate, Passiflora edulis ( P. edulis ) fruit juice (ZuFru) has antitumor activity, but whether a mechanism is through modulation of cell lipids is unknown. T o establish if ZuFru modifies cholesterol and triglycerides in SW480 and SW620. ZuFru composition was studied by phytochemical march; antiproliferative activity by sulforhodamine B, cholesterol , and triglycerides by Folch method. Z ufru contains anthocyanins, flavonoids, alkaloids , and tannins. Cell lines showed differences in their growth rate ( p =0.049). At 39.6 µg/m L of ZuFru, cell viability was decreased: SW480 (45.6%) and SW620 (45.1%). In SW480, cholesterol (44.6%) and triglycerides (46.5%) decreased; In SW620, cholesterol decreased 14.8% and triglycerides increased 7%, with significant differences for both lines. A ntiproliferative activity of ZuFru could be associated with the inhibition of intracellular biosynthesis of cholesterol and triglycerides in SW480. Action mechanisms need to be further investigated.

Las células cancerosas modifican el metabolismo lipídico para proliferar; el zumo de fruta (ZuFru) de Passiflora edulis ( P. edulis ) tiene activida d antitumoral, sin embargo, se desconoce si se involucran los lípidos celulares. E stablecer si ZuFru modifica colesterol y triglicéridos en células SW480 y SW620. C omposición del ZuFru, actividad antiproliferativa, colesterol y triglicéridos. Se encontraro n antocianinas, flavonoides, alcaloides y taninos. Las líneas celulares mostraron diferencias en su tasa de crecimiento ( p =0 . 049); ZuFru 39,6 µg/ml se disminuyó la viabilidad celular; SW480 (45,6%) y SW620 (45,1%); en SW480 colesterol (44,6%) y triglicérid os (46,5%) en SW620, colesterol (14,8%) y los triglicéridos aumentaron 7%, con diferencias significativas para ambas líneas. La actividad antiproliferativa del ZuFru podría estar asociada a la inhibición de la biosíntesis intracelular de colesterol y de tr iglicéridos en SW480, pero no en SW620. Estos mecanismos de acción deben ser fuertemente investigados.

Protocolo de recuperación mejorada después de cirugía (ERAS) atenúa el estrés y acelera la recuperación en pacientes después de resección radical por cáncer colorrectal: Experiencia en la Clínica Universitaria Colombia / Enhanced Recovery After Surgery (ERAS) protocol attenuates stress and accelerates recovery in patients after radical resection for colorectal cancer: Experience at Clínica Universitaria Colombia

Introducción. El conjunto de estrategias de recuperación mejorada después de la cirugía (ERAS, por sus siglas en inglés) constituye un enfoque de atención multimodal y multidisciplinario, cuyo propósito es reducir el estrés perioperatorio de la cirugía, disminuir la morbilidad y acortar la estancia hospitalaria. Este estudio tuvo como objetivo describir los resultados clínicos de pacientes sometidos a cirugía por cáncer colorrectal, identificando las complicaciones principales y los factores perioperatorios relacionados con el alta temprana. Métodos. Se analizaron los pacientes consecutivos sometidos a cirugía colorrectal entre los años 2020 y 2023, todos los cuales siguieron el protocolo ERAS institucional. Se evaluaron las características clínicas, los factores perioperatorios, los desenlaces postoperatorios y la tasa global de adherencia al protocolo. Resultados. Un total de 456 pacientes fueron sometidos a cirugía colorrectal, 51% de sexo masculino, con edad media de 60 años. La mayoría de las intervenciones se realizaron por laparoscopia (78 %), con una tasa de conversión del 14,5 %. Las complicaciones postoperatorias incluyeron fuga anastomótica (4,6 %), sangrado, infección intraabdominal y obstrucción intestinal. La estancia hospitalaria promedio fue de 4 días y la mortalidad del 2,8 %. La tasa global de adherencia al protocolo ERAS fue del 84,7 %. Conclusiones. El enfoque combinado de cirugía laparoscópica y protocolo ERAS es factible, seguro y se asocia con una estancia hospitalaria más corta. La implementación y adherencia al protocolo ERAS no solo mejora los resultados postoperatorios, sino que también resalta la importancia de acceder a datos sólidos, permitiendo mejorar la atención perioperatoria local.

Introduction. The Enhanced Recovery After Surgery (ERAS) protocol is a multimodal, multidisciplinary approach to care, the purpose of which is to reduce the perioperative stress of surgery, decrease morbidity, and shorten hospital stay. This study aimed to describe the clinical outcomes of patients undergoing surgery for colorectal cancer, identifying the main complications and perioperative factors related to early discharge. Methods. Consecutive patients undergoing colorectal surgery between 2020 and 2023 were analyzed, who followed the institutional ERAS protocol. Clinical characteristics, perioperative factors, postoperative outcomes, and overall protocol adherence rate were evaluated. Results. A total of 456 patients underwent colorectal surgery, 51% male, with a mean age of 60 years. Most interventions were performed laparoscopically (78%), with a conversion rate of 14.5%. Postoperative complications included anastomotic leak (4.6%), followed by bleeding, intra-abdominal infection, and intestinal obstruction. The average hospital stay was 4 days and mortality was 2.8%. The overall adherence rate to the ERAS protocol was 84.7%. Conclusions. The combined approach of laparoscopic surgery and ERAS protocol is feasible, safe, and associated with a shorter hospital stay. Implementation and adherence to the ERAS protocol not only improves postoperative outcomes, but also highlights the importance of accessing solid data, allowing for improved local perioperative care.

Probiotics intervention in colorectal cancer: From traditional approaches to novel strategies / 中华医学杂志(英文版)

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status. These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis, metabolism, and immune response. The disruption of microbiota, known as dysbiosis, has been implicated in many intestinal diseases, including colorectal cancer (CRC). As the third most common cancer and the second leading cause of cancer-related death worldwide, CRC poses a significant health burden. There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes. Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment. Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC, alleviating treatment-related side effects, and potentiating the efficacy of anticancer therapy, which is the key to successful translation to clinical practice. This paper aims to review the traditional probiotics and new interventions, such as next-generation probiotics and postbiotics, in the context of CRC. The underlying mechanisms of probiotic anti-cancer effects are also discussed, including the restoration of microbial composition, reinforcement of gut barrier integrity, induction of cancer cell apoptosis, inactivation of carcinogens, and modulation of host immune response. This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy. Despite all the promising findings presented in studies, the evaluation of potential risks, optimization of delivery methods, and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis / 中华医学杂志(英文版)

BACKGROUND@#Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology.@*METHODS@#The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.@*RESULTS@#The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12-0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05-0.92, P = 0.037).@*CONCLUSIONS@#We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Adenoma detection rate and polyp detection rate among gastroenterology fellows and consultants in a tertiary hospital in the Philippines: A cross-sectional study

Background and Objective@#Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer mortality worldwide. Likewise in the Philippines, the prevalence of CRC has shown to be increasing. Colonoscopy, a screening procedure for CRC, has parameters to gauge quality of detection. One of which is the Adenoma Detection Rate (ADR). Higher ADR has been linked to improved cancer detection. This study aimed to determine the ADR and Polyp Detection Rate (PDR) among Gastroenterology practitioners in a tertiary government university hospital in the Philippines, estimate ADR from PDR, and identify factors associated with ADR.@*Methods@#An analytical, cross-sectional study among patients who underwent colonoscopy for the years 2021 and the first half of 2022 at the Central Endoscopy Unit (CENDU) of the Philippine General Hospital. Demographic data of fellows and consultants were collected through an online form, while those from patients were obtained from electronic records. Colonoscopy details and histopathology results were accessed through the hospital’s Open Medical Record System (MRS). ADR, PDR, and estimated ADR were computed using established formulas. To evaluate the strength of the relationship between the estimated and actual ADR, Pearson’s correlation coefficient was used. Chi-square analysis, Mann-Whitney U test, and Kruskal-Wallis H test were performed to identify the factors that might influence the ADR. A cut-off of p < 0.05 was considered statistically significant.@*Results@#The total computed ADR of consultants and fellows combined is 22%. The difference between the ADRs of Gastroenterology consultants and Fellows-in-Training is statistically significant at 31.6% and 18.7%, respectively (p= 0.017). The total Polyp Detection Rate is 57.6% while the weighted group average Adenoma to Polyp Detection Rate Quotient (APDRQ) is 0.4085 or 40.85%. The estimated ADR has a moderate degree of correlation with the actual ADR when an outlier was excluded (r=0.521 (95% CI, 0.072-0.795, p=0.0266). Significant factors related to ADR include endoscopists’ years of practice (p=0.020), number of colonoscopies done (p=0.031), and patient tobacco use (p=0.014).@*Conclusion@#The overall ADR among consultants and fellows is at par with the standard guidelines. A moderate degree of correlation exists between actual and estimated ADR when an outlier is excluded; however, more studies are needed to determine the APDRQ in the wider local setting. Longer years in practice, total number of colonoscopies performed, and patient tobacco use are associated with increased ADR.

A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis / 中华医学杂志(英文版)

BACKGROUND@#Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.@*METHODS@#We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.@*RESULTS@#The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1 . The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.@*CONCLUSION@#The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1 .@*TRIAL REGISTRATION@#No. NCT00454519 ( https://clinicaltrials.gov/ ).

Current status of global colorectal cancer prevalence, prevention and control / 中华肿瘤杂志

Objective: This paper provides a brief overview of the epidemiology of colorectal cancer in China and around the world, and discusses how to prevent colorectal cancer to reduce its disease burden. Method: Using the official database of GLOBOCAN 2020, the China Cancer Registry Annual Report compiled by the National Cancer Center, and data from CONCORD-3.Data management was performed by Microsoft Excel 2016 and R 4.2.1 Relevant graphs were generated using the ggplot2 package for result visualization. Result: An estimated 1 931 590 people were diagnosed with colorectal cancer worldwide in 2020 with an age-standardized incidence rate of 19.5 per 100 000. There were about 935 173 deaths caused by colorectal cancer internationally, with an age-standardized mortality rate of 9.0 per 100 000. Overall, colorectal cancer was the fourth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. In China, the age-standardized incidence rate and mortality rate of colorectal cancer was 17.3 per 100 000 and 7.8 per 100 000, respectively. Gender differences in trends were observed, with a decreasing trend in incidence and mortality among females and an increasing trend in incidence and mortality among males. The primary risk factors for colorectal cancer include age, genetic factors, gastrointestinal disorders, dietary habits, and lifestyle et al. Conclusions: Colorectal cancer poses a significant burden globally and in China. The occurrence of colorectal cancer is closely related to physiology, genetics, behavioral habits, lifestyle, and disease factors. To better control the colorectal cancer burden with the lowest cost, specific measures should be taken to reduce exposure to established risk factors. By combining the disease prevention and control strategies of tertiary prevention in China with the characteristic factors of colorectal cancer, the incidence and mortality of colorectal cancer may be effectively controlled.

Current status of global colorectal cancer prevalence, prevention and control / 中华肿瘤杂志

Objective: This paper provides a brief overview of the epidemiology of colorectal cancer in China and around the world, and discusses how to prevent colorectal cancer to reduce its disease burden. Method: Using the official database of GLOBOCAN 2020, the China Cancer Registry Annual Report compiled by the National Cancer Center, and data from CONCORD-3.Data management was performed by Microsoft Excel 2016 and R 4.2.1 Relevant graphs were generated using the ggplot2 package for result visualization. Result: An estimated 1 931 590 people were diagnosed with colorectal cancer worldwide in 2020 with an age-standardized incidence rate of 19.5 per 100 000. There were about 935 173 deaths caused by colorectal cancer internationally, with an age-standardized mortality rate of 9.0 per 100 000. Overall, colorectal cancer was the fourth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. In China, the age-standardized incidence rate and mortality rate of colorectal cancer was 17.3 per 100 000 and 7.8 per 100 000, respectively. Gender differences in trends were observed, with a decreasing trend in incidence and mortality among females and an increasing trend in incidence and mortality among males. The primary risk factors for colorectal cancer include age, genetic factors, gastrointestinal disorders, dietary habits, and lifestyle et al. Conclusions: Colorectal cancer poses a significant burden globally and in China. The occurrence of colorectal cancer is closely related to physiology, genetics, behavioral habits, lifestyle, and disease factors. To better control the colorectal cancer burden with the lowest cost, specific measures should be taken to reduce exposure to established risk factors. By combining the disease prevention and control strategies of tertiary prevention in China with the characteristic factors of colorectal cancer, the incidence and mortality of colorectal cancer may be effectively controlled.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Quality assessment of colonoscopies performed by resident physicians in colorectal surgery

Introduction: Colorectal cancer is the third most common malignant neoplasm worldwide, with ~ 150 thousand new cases each year. Screening policies have brought significant progress due to the possibility of early diagnosis and polyp resection. Therefore, there is a need for continuous evaluation of the quality of colonoscopies based on well-established criteria in the literature. Materials and Methods: The present retrospective study assesses the quality of colonoscopies performed at a tertiary hospital, comparing resident physicians with their preceptors. A total of 422 preceptor exams and 115 resident exams were evaluated, with a comparison of the adenoma detection rate, cecal intubation rate, examination time, and bowel preparation quality. Results: The adenoma detection rate in the exams performed by preceptors was of 46.9%, while in those performed by residents, it was of 35.2% (p = 0.038). The cecal intubation rate was of 98.6% in the preceptor group and of 94.8% in the resident group (p = 0.025). The median total examination time was of 13 minutes and 42 seconds in the preceptor group and of 19 minutes and 22 seconds in the resident group (p < 0.005). Conclusion: During their training, resident physicians perform an adequate number of colonoscopies, which enables them to achieve adenoma detection rates, cecal intubation and examination times within the limits proposed by the literature. (AU)

Mortalidade por Câncer de Cólon e Reto no Brasil e suas Regiões entre 2006 e 2020 / Mortality due to Colon and Rectal Cancer in Brazil and its Regions between 2006 and 2020

No Brasil, estima-se a ocorrência de 704 mil casos novos de câncer para cada ano do triênio 2023-2025, sendo o câncer de cólon e reto (CCR) o tipo de neoplasia responsável pela terceira maior taxa de mortalidade para ambos os sexos. Objetivo: Analisar a tendência temporal de mortalidade prematura por CCR de 2006 a 2020, em ambos os sexos, no Brasil e em suas cinco Macrorregiões, e avaliar o alcance da meta proposta pelo Plano de Ações Estratégicas para o Enfrentamento das Doenças Crônicas não Transmissíveis no Brasil 2011-2022 do Ministério da Saúde (MS) em relação ao CCR. Método: Estudo de séries temporais das taxas de mortalidade prematura e padronizada de CCR (CID-10: C18-21) tendo como população de estudo a do Brasil, com dados obtidos a partir do Sistema de Informação sobre Mortalidade do DATASUS de 2006 a 2020. Resultados: As taxas de mortalidade prematura por CCR apresentaram aumento linear ao longo do período observado, porém com importantes diferenças regionais. Em relação ao CCR, a meta proposta pelo plano do MS não foi alcançada. Conclusão: Houve um aumento das taxas de mortalidade prematura por CCR no Brasil, tendência esperada em países em desenvolvimento. Por ser um câncer que envolve fatores de risco modificáveis, são importantes ações contínuas voltadas para o manejo desses fatores, tais como políticas nacionais de promoção de saúde. Além disso, são necessários estudos que subsidiem políticas preventivas de programas de rastreamento e diagnóstico precoce.

In Brazil, 704 thousand new cases of cancer were estimated for each year of the triennium 2023-2025, and colon and rectal cancer (CRC) is the type of neoplasm responsible for the third highest mortality rate for both sexes in the country. Objective: To analyze the temporal trend of premature mortality by CRC from 2006 to 2020, for both sexes, in Brazil and its five macroregions, and to evaluate whether the goal proposed by the Strategic Action Plan for Tackling Chronic non Communicable Diseases in Brazil 2011-2022 of the Ministry of Health (MH) in relation to CCR has been met. Method: Time series study of standardized premature mortality rates by CRC (ICD-10: C18-21); the study population is Brazil's population obtained from DATASUS' Mortality Information System from 2006 to 2020. Results: Premature mortality rates by CRC in Brazil and in all five macroregions increased linearly over the period investigated, but with important regional differences. The target proposed by the MH's Plan for CRC was not met. Conclusion: There was an increase in premature mortality rates by CRC in Brazil, a trend expected for developing countries. As it is a type of cancer that involves modifiable risk factors, continuous actions to manage these factors are important, such as national health promotion policies. Furthermore, studies are needed to support preventive policies for screening and early diagnosis programs

En el Brasil, se estimó la aparición de 704 000 nuevos casos de cáncer para cada año del período 2023-2025, siendo el cáncer de colorrectal (CCR) el tipo de neoplasia responsable de la tercera mayor tasa de mortalidad para ambos sexos en el país. Objetivo: Analizar la tendencia en el tiempo de la mortalidad prematura por CCR en el período de 2006 a 2020, en ambos sexos, en el Brasil y sus 5 macrorregiones, y evaluar si fue alcanzada la meta propuesta por el Plan de Acción Estratégica para el Enfrentamiento de las Enfermedades Crónicas no Transmisibles en el Brasil 2011-2022 del Ministerio de Salud (MS) con relación a la CCR. Método: Estudio de series de tiempo de tasas de mortalidad prematura estandarizadas por CCR (CIE-10: C18-21) utilizando como población de estudio toda la población del Brasil, con datos obtenidos del Sistema de Información sobre Mortalidad del DATASUS de 2006 a 2020. Resultados: Las tasas de mortalidad prematura por CCR en el Brasil y en las cinco regiones mostraron un aumento lineal durante el período observado, pero con importantes diferencias regionales. Con relación al CCR, la meta propuesta por el Plan del MS no fue alcanzada. Conclusión: Hubo un aumento de las tasas de mortalidad prematura por CCR en el Brasil, tendencia esperada en países en desarrollo. Al tratarse de un tipo de cáncer que involucra factores de riesgo modificables, son importantes las acciones continuas encaminadas a gestionar estos factores, como las políticas nacionales de promoción de la salud del CCR. Además, se necesitan estudios que respalden las políticas preventivas para los programas de detección y diagnóstico temprano

Clinical outcomes of the liver-first approach in the management of synchronous colorectal liver metastases: a retrospective study

Introduction: Almost 25% of colorectal cancer (CRC) patients have synchronous colorectal liver metastasis (SCLM) coinciding with the disease diagnosis. Liver-first approach for the treatment of SCLM involves neoadjuvant chemotherapy, subsequent liver resection, and then primary tumor resection. This strategy is adopted as the prognosis of the disease depends mainly on the metastases, not the primary tumor. This study aims to evaluate the feasibility of the liver-first approach and clinical prognosis in managing SCLM. Materials and Methods: This retrospective study included 25 patients with SCLM from July 2015 to July 2020. All patients were subjected to a liver-first approach with an "intention-to-treat" approach. Follow-up was planned for at least 3 years. Data were collected from the hospital records and included survival rates and univariate analyses of the prognostic factors, such as gender, age, and number of chemotherapy cycles to evaluate their effect on the survival probability. Results: Nineteen patients completed the treatment paradigm. Long-term outcomes reported a median overall survival (OS) of 32 months. One-year and 3-year survival probabilities were 89.5% and 42.1%, respectively. The median disease-free survival was 13 months. The number of metastatic lesions, unilobar versus bilobar disease, and the frequency of administered chemotherapy cycles significantly affected survival (p < 0.05). Seven patients (36.84%) remained disease free (no recurrence) while 2 patients (10.53%) survived with recurrence. The overall mortality included 10 deaths (52.63%) due to recurrence. Conclusion: Synchronous colorectal liver metastasis treated with the liver-first approach achieved a notable overall advantage. However, the recurrence rate remained relatively high. (AU)

Estrategias para mejorar la tasa de detección de adenomas y pólipos serrados durante una colonoscopia / Strategies to improve the detection rate of adenomas and serrated polyps during a colonoscopy

Adenoma detection rate (ADR) is a key quality indicator in screening colonoscopy, closely linked to colorectal cancer (CRC) prevention. Currently, the minimum recommended ADR is > 30% with an aspirational goal of > 35%; and the sessile serrated lesion detection rate (SSLDR) minimum is > 7% with an aspirational goal of > 10%. Improving the detection of adenomas and serrated lesions involves rigorous bowel preparation, using the validated Boston Bowel Preparation Scale (BBPS) with an adequate or superior score (≥ 6, with each segment ≥ 2: right-transverse-left) (minimum > 90% and > 95% aspirational goal). The most basic strategy is to implement split-dose bowel preparation regimens. A minimum withdrawal time of 6 minutes, ideally extended to 9 minutes, improves ADR and SSLDR, especially in the proximal colon. Incorporating techniques such as double examination of the right colon (retroflexion or second forward view), water-assisted colonoscopy, enhanced imaging endoscopy technologies (e.g., NBI, TXI, LCI, BLI), distal attachment devices, artificial intelligence systems (CADe), along with monitoring, feedback, continuing education, and teamwork, are key strategies to increase ADR and SSLDR, consequently, reduce the risk of post-colonoscopy or interval CRC.

La tasa de detección de adenomas (ADR) es un indicador de calidad fundamental en la colonoscopia de tamizaje, estrechamente relacionado con la prevención del cáncer colorrectal (CCR). Actualmente la ADR mínima reco- mendada es > 30% y aspiracional > 35%; y la tasa de detección de lesiones serradas sésiles (SSLDR) mínima > 7% y aspiracional > 10%. Mejorar la detección de adenomas y pólipos serrados implica una preparación intestinal rigurosa, utilizando la escala validada de Boston con puntuación adecuada o superior (≥ 6, con cada segmento ≥ 2: derecho-transverso-izquierdo) (mínimo > 90% y > 95% meta aspiracional). Siendo la estrategia más básica implementar regímenes de preparación intestinal en dosis divididas. Un tiempo de retirada mínimo de 6 minutos, idealmente extendido a 9 minutos, mejora la ADR y SSLDR, especialmente en el colon proximal. La incorporación de técnicas como la doble inspección del colon derecho (retroflexión o segunda visión frontal), la colonoscopia asistida por agua, tecnologías de endoscopia con imagen mejorada (ej: NBI, TXI, LCI, BLI), dispositivos de fija- ción distal, sistemas de inteligencia artificial (CADe), junto con la monitorización, retroalimentación, educación continua y trabajo en equipo, son estrategias clave para aumentar la ADR y SSLDR, en consecuencia, reducir el riesgo de CCR posterior de colonoscopia o intervalo.