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.

Logistíca e resultados de um programa de prevenção do câncer colorretal em um município do Sertão de Alagoas / Logistics and results of a colorectal cancer screening program in a municipality in the hinterland of alagoas

ABSTRACT Background: Colorectal cancer (CRC) has high mortality rates worldwide. In Brazil, it is the second most common cancer in both sexes. Delay in detecting premalignant lesions contributes to increased morbidity and mortality. In this scenario, the Piranhas project was created to track CRC in a low-income population in the hinterland of Alagoas. Objective: The study aimed to establish the main strategies and verify the feasibility of implementing a CRC tracking program and demonstrate the results obtained in the CRC Prevention Campaign in Piranhas/AL. Methods: The program took place in Piranhas, Alagoas, Brazil, through public-private partnerships. Individuals aged between 50 and 70 years of age were included for screening with a fecal occult blood test (FOBT) and colonoscopy in positive cases. Patient data were collected on standard forms. Results: A total of 2152 patients, aged between 50 and 70 years, were screened, 130 of which underwent colonoscopy. Several preneoplastic lesions were detected in 58 patients. The adenoma detection rate (ADR) was 33.85%. Conclusion: The study proved to be effective and viable since 44.6% of the program participants, who underwent screening with FOBT, followed by colonoscopy in positive cases, had some type of preneoplastic lesion. In addition, the program generated a significant social impact on the population of Piranhas due to the opportunity to diagnose and treat CRC precursor lesions.

RESUMO Contexto: O câncer colorretal (CCR) possui altas taxas de mortalidade em todo mundo. No Brasil é o segundo câncer mais comum em ambos os sexos. O atraso na detecção de lesões pré-malignas contribui com o aumento da morbimortalidade. Neste cenário, o projeto Piranhas foi criado para rastrear o CCR em uma população carente do sertão alagoano. Objetivo: O estudo teve como meta estabelecer as principais estratégias e verificar a viabilidade da implementação de um programa de rastreamento do CCR, assim como demonstrar os resultados obtidos na Campanha de prevenção de CCR no município de Piranhas/AL. Métodos: O programa aconteceu em Piranhas, Alagoas, Brasil, através de parcerias público-privadas. Foram incluídos indivíduos entre 50 e 70 anos para triagem com pesquisa de sangue oculto nas fezes (PSOF) e colonoscopia dos casos positivos. Os dados dos pacientes foram coletados em formulários padrão. Resultados: Foram rastreados um total de 2152 pacientes com idade entre 50 e 70 anos, sendo destes, 130 submetidos à colonoscopia. Várias lesões pré-neoplásicas foram detectadas em 58 pacientes. A taxa de detecção de adenoma foi de 33,85%. Conclusão: O estudo demonstrou-se eficaz e viável, uma vez que 44,6% dos participantes do programa que realizaram a triagem com PSOF seguido de colonoscopia nos casos positivos apresentava algum tipo de lesão pré-neoplásica. Além disso, o programa gerou grande impacto social na população de Piranhas, pela oportunidade de diagnóstico e tratamento de lesões precursoras do CCR.

Laparorrafia en pacientes con cáncer colorrectal. Hospital Enrique Cabrera, 2019-2021

Fundamento aún no se ha establecido una técnica ideal que permita realizar el cierre laparotómico que garantice la disminución de complicaciones. Objetivo comparar los resultados del cierre de la pared abdominal mediante puntos subtotales internos y puntos totales en pacientes intervenidos por cáncer colorrectal. Métodos: se realizó un estudio descriptivo, prospectivo y transversal en el Hospital General Docente Dr. Enrique Cabrera, en el trienio 2019-2021, con 80 pacientes intervenidos por cáncer colorrectal. Se empleó la prueba Chi-cuadrado, la prueba exacta de Fisher y la prueba U de Mann-Whitney, entre otros. Resultados el tumor se localizó en colon sigmoide en 35 % de los casos de los pacientes con cierre de puntos totales; y en 31,7 % del grupo con cierre mediante puntos subtotales. La cirugía fue urgente en 80 % del grupo con cierre de puntos totales; y electiva en 75 % de los de cierre con puntos subtotales. La incisión fue media supra e infraumbilical en 70 % de los pacientes del grupo con cierre de puntos totales; y xifopubiana en 66,7 % de los del cierre con puntos subtotales. Se presentaron medianas de 3 ± 2 y 1 ± 0 complicaciones para los de cierre con puntos totales y cierre con puntos subtotales, respectivamente. La mediana de la estadía hospitalaria fue mayor en el grupo con cierre de puntos totales (8 ± 6 días). Conclusiones en los pacientes donde se aplicaron puntos subtotales internos para el cierre de la pared abdominal, los resultados fueron mejores que en grupo donde se emplearon puntos totales.

Foundation an ideal technique has not been established yet to allow laparotomic closure to guarantee the reduction of complications. Objective to compare the results of abdominal wall closure using internal subtotal points and total points in patients operated on for colorectal cancer. Methods a descriptive, prospective and cross-sectional study was carried out at the Dr. Enrique Cabrera General Teaching Hospital, from 2019 to 2021, with 80 patients operated on for colorectal cancer. The Chi-square test, Fisher's exact test and the Mann-Whitney U test, among others, were used. Results the tumor was located in the sigmoid colon in 35% of patients with total suture closure; and in 31.7% of the group with closure by subtotal points. Surgery was urgent in 80% of the group with total stitch closure; and elective in 75% of the closing cases with subtotal points. The incision was median supra and infraumbilical in 70% of the patients in the group with total suture closure; and xiphopubic in 66.7% of those at closure with subtotal points. There were medians of 3 ± 2 and 1 ± 0 complications for closure with total stitches and closure with subtotal stitches, respectively. Median hospital stay was longer in the total stitch closure group (8 ± 6 days). Conclusions in the patients where internal subtotal sutures were applied for abdominal wall closure, the results were better than in the group where total sutures were used.

Cáncer colorrectal post-colonoscopia: Evaluación de una cohorte en sus características clínicas, colonoscópicas, sobrevida y sus causas según la Organización Mundial de Endoscopia

Cáncer colorrectal post-colonoscopia (CCRP) es el tumor que aparece posterior a una colonoscopia normal antes de cumplirse el tiempo establecido para seguimiento endoscópico. Origen multifactorial, refleja la calidad de la colonoscopia y las diferentes biologías tumorales entre los cánceres colorrectales detectados (CCRD) y el CCRP. Nuestro objetivo es describir las características del CCRP en nuestro medio, identificar factores de riesgo, discriminar sus causas según la Organización Mundial de Endoscopia (OME) y determinar el efecto en la sobrevida del paciente. El estudio se realizó en pacientes con cáncer-colorrectal (CCR) atendidos en consulta de gastro-oncología de dos instituciones en Medellín-Colombia, entre enero de 2012 y diciembre de 2021 que se habían sometido a una colonoscopia en los 6 a 36 meses anteriores a la colonoscopia en la que se diagnosticó el CCR. 919 pacientes durante 10 años por CCR, 68 casos de CCRP (6,9%), se encontró que se presenta con más frecuencia en pacientes mayores (74 vs. 66 años; p=0,03), con antecedentes de pólipos adenomatosos (36,8% vs. 20,1%; p=0,01) y en colon derecho (57,4% vs. 40,6%; p=0,006), con una tendencia en pacientes con diverticulosis (41,2% vs. 31,3%; p=0,05) y diabetes (25% vs. 14%; p=0,06); menor sobrevida a 5 y 10 años (58%-55,2% vs. 67%-63%; p<0,001). Según la OME, los CCRP se presentaron en 61,3% por lesiones omitidas en colonoscopias inadecuadas, 29% colonoscopias adecuadas y 9,7% resecciones incompletas de adenomas. En conclusión, la tasa de CCRP fue de 6,9%, con mayor propensión en pacientes de mayores, antecedente de resección de pólipos, y en colon derecho. Acorde a la OME, las lesiones omitidas más frecuentemente se relacionaron con colonoscopias inadecuadas. Los pacientes con CCRP tienen menor sobrevida.

Post-colonoscopy colorectal cancer (PCCRC) is a tumor that appears after a normal colonoscopy before the established time for the endoscopic follow up. Its origin reflects the quality of the colonoscopy and the different tumoral biologics between the CRC and the CRCPC. Our aim is to describe the characteristics of the PCCRC in our region, to identify risk factors, to discriminate the potential causes according to the World Endoscopý Organization (WEO) and to determine its impact in the patient's survival. We studied patients with colorectal cancer (CRC) attended at the gastro-oncology clinic of two institutions of Medellin-Colombia, between January 2012 and December 2021 that had been submitted to a colonoscopy between 6-36 months before the colonoscopy in which the CRC was diagnosed. 919 patients during 10 years for CRC, 68 cases of PCCRC (6.9%); It was more frequent in older patients (74 vs. 66 years; p=0.03), with background of adenomatous polyps (36.8% vs. 20.1%; p=0.01) and in right colon (57.4% vs. 40.6%; p=0.006), with a tendency in patients with diverticulosis (41.2% vs. 31.3%; p=0.05) and diabetes (25% vs. 14%; p=0.06); less survival at 5 and 10 years (58% and 55.2% vs. 67% and 63%; p<0.001). According to the WEO, the PCCRC presents in 61.3% because of abnormal findings omitted in inadequate colonoscopies, 29% in a suitable colonoscopy and 9.7% incomplete resections of adenomas. In conclusion, the rate of PCCRC was 6.9% with more propension in older patients, a background of polyp resection, and proximal colon. According to the WEO, the abnormal findings omitted more frequently were related with inadequate colonoscopies. The patients with PCCRC had less survival.

Cáncer colorectal en el embarazo. Reportes de caso

El cáncer colorrectal (CCR) durante el embarazo es una neoplasia poco frecuente, con una incidencia entre el 0,07- 0,1% en la población. Para un diagnóstico preciso es necesaria una alta sospecha y con ello realizar pruebas diagnósticas oportunas. Cuando no se tiene sospecha ni se busca el diagnóstico, el pronóstico suele ser malo, ya que muchas veces se halla en estado avanzado. Presentamos los casos de dos gestantes de 27 y 31 años, diagnosticadas de adenocarcinoma colorrectales medianamente diferenciados a las 29 y 30 semanas de gestación, respectivamente. Debido a la importancia de realizar un diagnóstico oportuno para mejorar la sobrevida de las pacientes, se realizó una búsqueda de información en la literatura en relación con el diagnóstico, manejo y pronóstico de esta patología.

Colon rectal cancer (CRC) during pregnancy is a rare neoplasia, with an incidence between 0.07-0.1% in the population. For an early diagnosis, a high suspicion is necessary and with it, timely diagnostic tests are carried out. When there is no suspicion and no diagnosis is sought, the prognosis is usually poor since it is often in an advanced state. We present the cases of two pregnant women aged 27 and 31 diagnosed with moderately differentiated colorectal adenocarcinoma at 29 and 30 weeks of gestation, respectively. Due to the importance of making an opportune diagnosis to improve the survival of the patients, a search of information was carried out in the literature in relation to the diagnosis, management and prognosis of this pathology.

Atenção à saúde do estomizado na rede de atenção à saúde na perspectiva de enfermeiros / Health care of the stomized in the health care network from the perspective of nurses / Atención sanitaria de estomizados en la red de salud desde la perspectiva de enfermeras

Objetivo: Identificar como é o cuidado oferecido às pessoas que vivem com estomias na rede de atenção à saúde na ótica dos enfermeiros. Métodos: Estudo qualitativo, descritivo, desenvolvido com 29 enfermeiros que atuavam na Rede de Atenção à Saúde que dispensam cuidados ao paciente com estomia. O referencial teórico metodológico utilizado foi a pesquisa social de Minayo, a qual apoia-se no materialismo histórico e dialético. Coleta de dados realizada nos meses de março e abril de 2018, por meio de uma entrevista semiestruturada. Realizada análise temática dos dados. Resultados: Foram identificadas fragilidades na comunicação na rede de atenção à saúde, bem como nas ações de cuidado efetivadas pelos enfermeiros às pessoas que vivem com estomas, demonstrou-se um cuidado centralizado e falha na atenção devido a falta de educação continuada. Conclusão: O cuidado aos estomizados possui pontos a serem melhorados como à definição de itinerário para este paciente, centralização do cuidado, garantia da continuidade do cuidado e integralidade, referência e contrarreferência, necessidade de uma comunicação efetiva entre as equipes de saúde que assistem estes pacientes bem como falta de educação continuada. (AU)

Objective: To identify how care is provided to people living with ostomy in the health care network from the perspective of nurses. Methods: Qualitative, descriptive study, developed with 29 nurses who worked in the Health Care Network who provide care to patients with ostomy. The methodological theoretical framework used was Minayo's social research, which is based on historical and dialectical materialism.Data collection carried out in March and April 2018, through a semi-structured interview. Thematic analysis of the data was carried out. Results: Weaknesses were identified in communication in the health care network, as well as in the care actions carried out by nurses to people living with stomas, demonstrating a centralized care and failure in care due to the lack of continuing education. Conclusion: The care of ostomy patients has points to be improved, such as defining an itinerary for this patient, centralization of care, ensuring continuity of care and completeness, referral and counter-referral, need for effective communication between the health teams that care for these patients as well as lack of continuing education. (AU)

Objetivo: Identificar cómo se atiende a las personas que viven con ostomía en la red asistencial desde la perspectiva del enfermero. Métodos: Estudio cualitativo, descriptivo, desarrollado con 29 enfermeras que laboraban en la Red de Atención de Salud que brinda atención a pacientes con ostomía. El marco teórico metodológico utilizado fue la investigación social de Minayo, que se basa en el materialismo histórico y dialéctico. Recolección de datos realizada en marzo y abril de 2018, mediante entrevista semiestructurada. Se realizó un análisis temático de los datos. Resultados: Se identificaron debilidades en la comunicación en la red de atención de salud, así como en las acciones de atención que realizan las enfermeras a las personas que viven con estoma, ubicando la atención centralizada y falla en la atención por falta de educación continua. Conclusión: La atención al paciente con ostomía tiene puntos a mejorar, como la definición de un itinerario para este paciente, la centralización de la atención, asegurar la continuidad y la integralidad de la atención, la derivación y contrarreferencia, la necesidad de una comunicación efectiva entre los equipos de salud que atienden. estos pacientes, así como la falta de educación continua. (AU)

Proteína C reactiva como biomarcador predictivo de fuga anastomótica en cirugía oncológica colorrectal: estudio de cohorte retrospectivo / C-reactive protein as a predictive biomarker of anastomotic leak in colorectal cancer surgery: A retrospective cohort study

Introducción. La fuga anastomótica es la complicación más grave del tratamiento quirúrgico del cáncer de colon por su alta morbimortalidad. El diagnóstico evidente, manifestado por la salida de contenido intestinal por drenajes o la herida quirúrgica, ocurre tardíamente (entre el 6º y 8º día). El objetivo de este trabajo fue estudiar la variación de los valores de la proteína C reactiva postoperatoria para hacer un diagnóstico precoz. Métodos. Estudio observacional, analítico, retrospectivo, de una cohorte de pacientes con neoplasia, en quienes se realizó cirugía oncológica con anastomosis intestinal, entre enero de 2019 y diciembre de 2021. Se midieron los valores en sangre de proteína C reactiva postoperatoria (1°, 3° y 5° días). Resultados. Se compararon 225 casos operados que no presentaron fuga con 45 casos con fuga. En los casos sin fuga, el valor de proteína C reactiva al 3º día fue de 148 mg/l y al 5º día de 71 mg/l, mientras en los casos con fuga, los valores fueron de 228,24 mg/l y 228,04 mg/l, respectivamente (p<0,05). Para un valor de 197 mg/l al 3º día la sensibilidad fue de 77 % y para un valor de 120 mg/l al 5º día la sensibilidad fue de 84 %. Conclusión. El mejor resultado de proteína C reactiva postoperatoria para detectar precozmente la fuga anastomótica se observó al 5º día. El valor de 127 mg/l tuvo la mejor sensibilidad, especificidad y valor predictivo negativo, lo cual permitiría el diagnóstico temprano y manejo oportuno de esta complicación

Introduction. Anastomotic leak is the most serious complication of surgical treatment of colon cancer due to its high morbidity and mortality. The obvious diagnosis manifested by the exit of intestinal content through drains or the operative wound, occurs late (between the 6th and 8th day). The objective of this work was to study the postoperative C-reactive protein values to make an early diagnosis. Methods. Observational, analytical, retrospective study of a cohort of patients undergoing colorectal surgery for neoplasia, between January 2019 and December 2021, who underwent oncological surgery with intestinal anastomosis and measured CRP blood values on 1st, 3rd and 5th post-operative days. Results. Two-hundred-twenty-five operated cases that did not present leaks were compared with 45 cases with leaks, with CRP values on the 3rd and 5th day of 148mg/l and 71mg/l in cases without leakage and CRP values of 228.24mg/l and 228.04 mg/l in cases with leakage on the 3rd and 5th day, respectively (p<0.05), CRP value of 197mg/l on the 3rd day has a sensitivity of 77%; CRP value of 120mg/l on the 5th day, has a sensitivity of 84%. Conclusions. The best result for CPR to early diagnosis of anastomotic leak was observed on the 5th day, having the value of 127 mg/l the best sensitivity, specificity and NPV, which would allow early diagnosis and timely management

Preoperative evaluation of sarcopenia in patients with colorectal cancer: a prospective study

SUMMARY OBJECTIVE: Colorectal cancer is the third most diagnosed malignant neoplasm in the world and the fourth leading cause of cancer mortality. The loss of muscle mass in oncological patients is the main aspect of cancer-related malnutrition. Associations between sarcopenia and poor outcomes, such as high postoperative mortality, chemotherapy toxicity, and reduced survival, have been recently described. The aim of this study was to prospectively assess the prevalence of preoperative sarcopenia in patients with colorectal cancer using validated methods to evaluate muscle strength, muscle mass, and physical performance. METHODOLOGY: This study included patients with colorectal cancer undergoing oncological staging at a Cancer Center in Brazil from May 2019 to March 2020 who had images from abdominal computed tomography available for analysis of body composition. The muscle strength test, physical performance, referred fatigue, and clinical and nutritional data were evaluated. RESULTS: A total of 31 patients were included, and most were diagnosed with colon cancer (77.4%) and clinical stage II in 41.9% of cases. The prevalence of probable sarcopenia was 22.6%; of these patients, sarcopenia was confirmed in 19.4%, and ultimately, 9.7% of the sample was classified as severe sarcopenia. We did not find a significant association between the presence of sarcopenia in our sample and age, sex, tumor staging, nutritional characteristics, referred patient fatigue, or postoperative complications. CONCLUSION: Considering the criteria established by the EWGSOP, the prevalence of preoperative sarcopenia in colorectal cancer patients was 19.4%.

Intervenciones endoscópicas para mejorar la tasa de detección de lesiones serradas durante la colonoscopia

El cáncer colorrectal (CCR) es una de las causas más frecuentes de mortalidad por cáncer en el mundo. Las lesiones serradas son responsables de 10 a 20% de todos los CCR. Los pólipos serrados, en particular los adenomas serrados sésiles (ASS) y adenomas serrados tradicionales (AST), tienen una apariencia sutil y localización proximal, y por ello presentan una alta tasa de lesiones perdidas. El objetivo de la presente revisión fue evaluar la evidencia disponible sobre el uso de diversas intervenciones endoscópicas para mejorar la tasa de detección de las lesiones serradas, para de esta forma, disminuir la mortalidad relacionada al CCR.

Colorectal cancer (CRC) is one of the most common causes of cancer mortality in the world. Serrated lesions are responsible for 10 to 20% of all CRCs. Serrated polyps, particularly sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA), have a subtle appearance and proximal location, and therefore have a high miss rate. The objective of this review was to evaluate the available evidence on the use of various endoscopic interventions for improving serrated lesion detection rate, thus reducing CRC related mortality.

Prevalence of colorectal cancer in 2020: a comparative analysis between China and the world / 中华肿瘤杂志

Objective: To demonstrate the disease burden and epidemiological characteristics of colorectal cancer in different regions by analyzing the incidence and mortality data in China and worldwide in 2020. Methods: Estimation of the incidence and mortality data of colorectal cancer were obtained from the GLOBOCAN 2020 database. The incidence, death, age standardized incidence rate (ASIR) and age standardized mortality rate (ASMR) of colorectal cancer in China and 20 regions in the world were compared. The correlation between the Human Development Index (HDI) and ASIR/ASMR was analyzed. Results: In 2020, the number of new cases of colorectal cancer in the world reached 1 931 600, and the number of deaths reached 935 200. The incidence and mortality in all regions of the world continued to rise in the age group above 50 years old. The morbidity and mortality in male were higher than those in female. East Asia ranked the highest number of incidence cases and deaths in the world, which were 740 000 and 360 100 respectively. There were significant differences in incidence and mortality among regions in the world. The highest ASIR and ASMR were observed in Northern Europe (33.61/100 000) and Eastern Europe (14.53/100 000), whereas the lowest ASIR and ASMR were both observed in South-Central Asia (5.46/100 000 and 3.16/100 000). HDI had significant exponential relationship with ASIR (r(2)=0.59, P<0.001) and ASMR (r(2)=0.38, P<0.001). There were 555 500 new cases and 286 200 death cases of colorectal cancer in China, accounting for about 30% of the world and more than 75% of East Asia. The ASIR of China was 24.07/100 000, ranking at the medium level, while the ASMR was 12.07/100 000, ranking at the high level of world. Conclusion: The incidence and mortality of colorectal cancer are highly correlated with HDI. China is one of the countries with the heaviest disease burden of colorectal cancer in the world.

The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice / 中华肿瘤杂志

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.

Construction of TRAF6 ubiquitin site 331 mutant colorectal cancer cell stable line and its effect on biological behavior of colorectal cancer cells / 中华肿瘤杂志

Objective: To investigate the effect of ubiquitin mutation at position 331 of tumor necrosis factor receptor related factor 6 (TRAF6) on the biological characteristics of colorectal cancer cells and its mechanism. Methods: lentivirus wild type (pCDH-3×FLAG-TRAF6) and mutation (pCDH-3×FLAG-TRAF6-331mut) of TRAF6 gene expression plasmid with green fluorescent protein tag were used to infect colorectal cancer cells SW480 and HCT116, respectively. The infection was observed by fluorescence microscope, and the expressions of TRAF6 and TRAF6-331mut in cells was detected by western blot. Cell counting kit-8 (CCK-8) and plate cloning test were used to detect the proliferation ability of colorectal cancer cells in TRAF6 group and TRAF6-331mut group, cell scratch test to detect cell migration, Transwell chamber test to detect cell migration and invasion, immunoprecipitation to detect the ubiquitination of TRAF6 and TRAF6-331mut with ubiquitinof lysine binding sites K48 and K63. Western blot was used to detect the effects of TRAF6 and TRAF6-331mut over expression on the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase mitogen-activated protein kinase (MAPK)/activating protein-1(AP-1) signal pathway. Results: The successful infection of colorectal cancer cells was observed under fluorescence microscope. Western blot detection showed that TRAF6 and TRAF6-331mut were successfully expressed in colorectal cancer cells. The results of CCK-8 assay showed that on the fourth day, the absorbance values of HCT116 and SW480 cells in TRAF6-331mut group were 1.89±0.39 and 1.88±0.24 respectively, which were lower than those in TRAF6 group (2.09±0.12 and 2.17±0.45, P=0.036 and P=0.011, respectively). The results of plate colony formation assay showed that the number of clones of HCT116 and SW480 cells in TRAF6-331mut group was 120±14 and 85±14 respectively, which was lower than those in TRAF6 group (190±21 and 125±13, P=0.001 and P=0.002, respectively). The results of cell scratch test showed that after 48 hours, the percentage of wound healing distance of HCT116 and SW480 cells in TRAF6-331mut group was (31±12)% and (33±14)%, respectively, which was lower than those in TRAF6 group [(43±13)% and (43±7)%, P=0.005 and 0.009, respectively]. The results of Transwell migration assay showed that the migration numbers of HCT116 and SW480 cells in TRAF6-331mut group were significantly lower than those in TRAF6 group (P<0.001 and P<0.002, respectively). The results of Transwell invasion assay showed that the number of membrane penetration of HCT116 and SW480 cells in TRAF6-331mut group was significantly lower than those in TRAF6 group (P=0.008 and P=0.009, respectively). The results of immunoprecipitation detection showed that the ubiquitin protein of K48 chain pulled by TRAF6-331mut was lower than that of wild type TRAF6 in 293T cells co-transfected with K48 (0.57±0.19), and the ubiquitin protein of K63 chain pulled down by TRAF6-331mut in 293T cells co-transfected with K63 was lower than that of wild type TRAF6 (0.89±0.08, P<0.001). Western blot assay showed that the protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-HCT116 cells were 0.63±0.08, 0.42±0.08 and 0.60±0.07 respectively, which were lower than those in TRAF6-HCT116 cells (P=0.002, P<0.001 and P<0.001, respectively). The expression level of AP-1 protein in TRAF6-HCT116 cells was 0.89±0.06, compared with that in TRAF6-HCT116 cells. The difference was not statistically significant (P>0.05). The protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-SW480 cells were 0.50±0.06, 0.51±0.04, 0.48±0.02, respectively, which were lower than those in TRAF6-SW480 cells (all P<0.001). There was no significant difference in AP-1 protein expression between TRAF6-331mut-SW480 cells and TRAF6-SW480 cells. Conclusion: The ubiquitin site mutation of TRAF6 gene at 331 may prevent the binding of TRAF6 and ubiquitin lysine sites K48 and K63, and then affect the expressions of proteins related to downstream NF-κB and MAPK/AP-1 signal pathways, and inhibit the proliferation, migration and invasion of colorectal cancer cells.

Combination of anlotinib and irinotecan in the second-line treatment of metastatic colorectal cancer: a multicenter phase 1/2 trial / 中华肿瘤杂志

Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.

Analysis of microsatellite instability in endometrial cancer: The significance of minimal microsatellite shift / 北京大学学报(医学版)

OBJECTIVE@#To analyze the differences and characteristics of microsatellite instability (MSI) in endometrial cancer (EMC), by using colorectal cancer (CRC) as control.@*METHODS@#In the study, 228 cases of EMC were collected. For comparative analysis, 770 cases of CRC were collected. Mismatch repair (MMR) expression was detected by immunohistochemistry (IHC), and microsatellite instability (MSI) was analyzed by PCR and capillary electrophoresis fragment analysis (MSI-PCR). MSI-PCR was detected using five mononucleotide repeat markers: BAT-25, BAT-26, NR-21, NR-24, and MONO-27.@*RESULTS@#In EMC, we found 27.19% (62/228) of deficient mismatch repair (dMMR) using IHC, significantly higher than CRC (7.79%, 60/770). Meanwhile, subclonal expression of MMR protein was found in 4 cases of dMMR-EMC and 2 cases of dMMR-CRC. According to the criteria of major micro-satellite shift, we found 16.23% (37/228) of MSI-high (MSI-H), 2.63% (6/228) of MSI-low (MSI-L), and 81.14% (185/228) of microsatellite stability (MSS) in EMC using MSI-PCR. The discor-dance rate between MMR-IHC and MSI-PCR in EMC was 11.84% (27/228). In CRC, we found 8.05% (62/770) of MSI-H, 0.13% (1/770) of MSI-L, and 91.82% (707/770) of MSS. The discordance rate between MMR-IHC and MSI-PCR in CRC was only 0.52% (4/770). However, according to the criteria of minimal microsatellite shift, 12 cases of EMC showed minimal microsatellite shift including 8 cases of dMMR/MSS and 4 cases of dMMR/MSI-L and these cases were ultimately evaluated as dMMR/MSI-H. Then, 21.49% (49/228) of EMC showed MSI-H and the discordance rate MMR-IHC and MSI-PCR in EMC decreased to 6.58% (15/228). No minimal microsatellite shift was found in CRC. Compared with EMC group with major microsatellite shift, cases with minimal microsatellite shift showed younger age, better tumor differentiation, and earlier International Federation of Gynecology and Obstetrics (FIGO) stage. There were significant differences in histological variant and FIGO stage between the two groups (P < 0.001, P=0.006).@*CONCLUSION@#EMC was more prone to minimal microsatellite shift, which should not be ignored in the interpretation of MSI-PCR results. The combined detection of MMR-IHC and MSI-PCR is the most sensitive and specific method to capture MSI tumors.

Value of detection of peripheral blood miR-194 combined with fecal miR-143 in the clinical screening of colorectal cancer / 国际肿瘤学杂志

Objective:To explore and analyze the value of detection of peripheral blood miR-194 combined with fecal miR-143 in the clinical screening of colorectal cancer.Methods:A total of 83 patients diagnosed with colorectal cancer by pathological tissue admitted to Huangshi Hospital of Traditional Chinese Medicine of Hubei Province from October 2019 to October 2020 were selected as the observation group, and 50 healthy volunteers who underwent physical examinations during the same period were selected as the control group. The levels of miR-194 in peripheral blood and miR-143 in feces were detected by fluorescence quantitative PCR. The level difference between the two groups and their correlations with clinicopathological parameters of patients with colorectal cancer were analyzed. Receiver operating characteristic (ROC) curve was drawn based on peripheral blood miR-194 and fecal miR-143 to evaluate their value for clinical screening of colorectal cancer.Results:The level of miR-194 in peripheral blood of the observation group was significantly higher than that of the control group (1.91±0.34 vs. 0.76±0.23) , while the level of fecal miR-143 in the observation group being significantly lower than that of the control group (1.85±0.43 vs. 2.48±0.62) , with statistically significant differences ( t=21.16, P<0.001; t=6.91, P<0.001) . Age of patients with colorectal cancer ( t=0.83, P=0.408; t=1.17, P=0.244) , TNM stage ( t=1.03, P=0.307; t=0.11, P=0.909) , lymphatic metastasis ( t=0.37, P=0.711; t=1.85, P=0.068) , distant metastasis ( t=0.41, P=0.683; t=1.72, P=0.089) were not correlated with the levels of peripheral blood miR-194 and fecal miR-143. When the cut-off value of miR-194 in peripheral blood was 1.82, the area under the ROC curve for the diagnosis of colorectal cancer was 0.76, and the diagnostic sensitivity and specificity were 79.38% and 74.29%, respectively. When the cut-off value of fecal miR-143 was 2.16, the area under the ROC curve for the diagnosis of colorectal cancer was 0.71. At this time, the diagnostic sensitivity and specificity were 76.54% and 73.61%, respectively. The area under ROC curve of combined detection for colorectal cancer was 0.81, and the diagnostic sensitivity and specificity were 83.46% and 75.43%, respectively. Conclusion:Peripheral blood miR-194 is highly expressed in colorectal cancer patients, and fecal miR-143 is low in colorectal cancer patients. The combined detection of the two has a high sensitivity for early diagnosis of colorectal cancer, which can provide important reference basis for early diagnosis of colorectal cancer and has high clinical application value.

Research progress on tumor microenvironment and immune combination therapy of MSS colorectal cancer / 国际肿瘤学杂志

In recent years, immunotherapy, especially immune checkpoint inhibitors, has shown obvious advantages in prolonging the survival of patients with advanced tumors, and the tumor microenvironment is one of the important factors affecting the efficacy of immunity. Patients with microsatellite-stable colorectal cancer exhibit immune responses in combination with immune checkpoint inhibitor therapy. In-depth exploration of the tumor microenvironment characteristics of microsatellite-stable colorectal cancer and the application of combined immune checkpoint inhibitor therapy can provide new ideas and directions for colorectal cancer immunotherapy.

Construction of postoperative prognosis model for patients with colorectal cancer / 国际肿瘤学杂志

Objective:To screen the factors influencing overall survival (OS) of patients undergoing radical resection for colorectal cancer (CRC) and to construct a prognostic model for OS of patients after CRC.Methods:The clinical data of 350 patients with stage Ⅰ-Ⅳ CRC who underwent radical resection in the People's Hospital of Wuhan University from March 2017 to December 2019 were collected retrospectively. Patients were divided into subgroups 0 ( n=70), 1 ( n=172), and 2 ( n=108) according to different preoperative systemic inflammation score (SIS). The relationship between different SIS, neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), systemic immune inflammation index (SII) and prognosis of CRC patients undergoing radical surgical resection were analyzed, and Cox regression models were used to perform univariate and multifactorial analyses of factors affecting patient prognosis, and column line graph models were constructed based on the results of multifactorial analyses. Results:By the deadline of follow-up, 80 of 350 CRC patients died, and the 5-year OS rate was 77.14%. The 5-year survival rates of patients in SIS group 0, group 1 and group 2 were 95.71%, 79.65% and 61.11% respectively, with a statistically significant difference ( χ2=30.19, P<0.001). Statistically significant differences in age ( χ2=19.40, P<0.001), tumor site ( χ2=8.18, P=0.017), T stage ( χ2=10.01, P=0.007), TNM stage ( χ2=14.80, P=0.001), tumor diameter ( χ2=13.91, P=0.001) and carcino-embryonic antigen (CEA) level ( χ2=10.12, P=0.006) among patients in SIS group 0, group 1 and group 2. The 5-year OS rates of patients in the low NLR and high NLR groups were 82.67% and 56.16% respectively, with a statistically significant difference ( χ2=24.96, P<0.001) ; the 5-year OS rates of patients in the low LMR and high LMR groups were 66.85% and 88.17% respectively, with a statistically significant difference ( χ2=22.45, P<0.001) ; the 5-year OS rates of patients in the low SII and high SII groups were 86.14% and 69.02% respectively, with a statistically significant difference ( χ2=14.76, P<0.001). Univariate analysis showed that age ( HR=2.58, 95% CI: 1.54-4.32, P<0.001), T stage ( HR=2.41, 95% CI: 1.24-4.68, P=0.009), N stage ( HR=3.03, 95% CI: 1.85-4.94, P<0.001), TNM stage ( HR=3.61, 95% CI: 2.15-6.04, P<0.001), nerve invasion ( HR=1.97, 95% CI: 1.27-3.08, P=0.002), vascular invasion ( HR=2.31, 95% CI: 1.49-3.59, P<0.001), preoperative SIS 1 score ( HR=5.09, 95% CI: 1.57-16.56, P=0.007), SIS 2 score ( HR=11.05, 95% CI: 3.42-35.65, P<0.001), NLR ( HR=2.97, 95% CI: 1.90-4.64, P<0.001), LMR ( HR=0.31, 95% CI: 0.19-0.52, P<0.001), and SII ( HR=2.50, 95% CI: 1.54-4.06, P<0.001) were all independent influence factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection; multivariate analysis showed that age >60 years ( HR=2.27, 95% CI: 1.31-3.91, P=0.003), TNM stage Ⅲ-Ⅳ ( HR=7.08, 95% CI: 1.89-26.59, P=0.004), and preoperative SIS 2 score ( HR=4.02, 95% CI: 1.09-14.83, P=0.037) were all independent risk factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection. The nomogram model built based on the screened variables has high prediction accuracy: the C-index of the nomogram was 0.75. Conclusion:Age>60 years old, TNM stage Ⅲ-Ⅳ, SIS 2 score are all independent risk factors for postoperative prognosis of colorectal cancer. The nomograph model constructed by this method has high prediction accuracy.

Research progress in reversing multidrug resistance in colorectal cancer / 国际肿瘤学杂志

Multidrug resistance impacts negatively upon the curative effect of chemotherapy and prognosis in colorectal cancer. There is a growing body of studies trying to develop drugs to overcome multidrug resistance against its common targets, including ATP-binding cassette proteins, metabolic enzymes, apoptotic genes, signaling pathways and genetic material, among which P-glycoprotein inhibitors and drugs disrupting DNA are deeply developed. Developing new inhibitors or combining existing inhibitors with conventional treatment are hopeful ways to overcome multidrug resistance in colorectal cancer.

Research progress of hyperthermic intraperitoneal chemotherapy in the treatment of colorectal cancer / 国际外科学杂志

Colorectal cancer is a common digestive system malignant tumor in the world, its incidence and mortality rate is in the forefront, with the social progress and the change of diet structure, the incidence of colorectal cancer is gradually increasing, and there is a trend of younger age. Among them, peritoneal metastasis is the main cause of death in patients with colorectal cancer. Non-surgical treatment has been used in the past, but the prognosis is poor. How to treat and prevent peritoneal metastasis in colorectal cancer patients and improve the prognosis of such patients as much as possible is a question worth our in-depth study. The hyperthermic intraperitoneal chemotherapy provides a new direction for the treatment of colorectal cancer patients, usually combined with surgical treatment, and co-applied in the clinic as a new treatment model. This article reviews the treatment mode of hyperthermic intraperitoneal chemotherapy, the choice of drugs, and the progress of research in the treatment and prevention of peritoneal metastasis in colorectal cancer.

Propensity score matching study of outcomes of elderly patients over 80 years of age with preoperative combined type 2 diabetes mellitus following laparoscopic colorectal cancer resection / 国际外科学杂志

Objective:To investigate the outcome after laparoscopic radical surgery for colorectal cancer in patients over 80 years of age with preoperative combined type 2 diabetes (T2DM).Methods:Clinical data of 919 patients who underwent colorectal cancer laparoscopic resection surgery in Shaanxi Provincial People′s Hospital from January 2015 to January 2019 were retrospectively analyzed. The propensity score matching (PSM) method was used for 1∶1 matching of gender, ASA score, preoperative serum albumin level, body mass index(BMI), preoperative haemoglobin level, clinical tumour pathology TNM staging, tumour location, other medical comorbidities and history of abdominal surgery and finally group of 104 elderly diabetic patients aged ≥80 years with combined T2DM were successfully matched with another 104 non-elderly non-diabetic patients <80 years without combined diabetes group. (1) To compare the differences in operating time, intraoperative bleeding, number of intraoperative blood transfusions, number of lymph nodes dissected, number of ICU treatments, postoperative time to exhaustion and postoperative hospital stay, and postoperative adjuvant chemotherapy between the two groups after matching. (2)To observe the difference in major postoperative complications between the two groups. (3) Patients in both groups were observed for three years post-operative survival rate during the follow-up period. SPSS 25.0 statistical software was used for data analysis. The survival analysis was carried aut by the Kaplan-Meier curve method in parallel and the Log-Rank test.Results:Both groups were balanced in terms of baseline variable after PSM ( P>0.05). There was no difference between the two groups in terms of operative time, intraoperative bleeding, number of intraoperative blood transfusions, number of lymph nodes dissected, or time to postoperative evacuation ( P>0.05). There was a statistically significant difference between two groups in the number of people admitted to the ICU for treatment ( χ2=4.04, P=0.042), and ≥80 years diabetic group was higher. The difference in the incidence of postoperative complications between the two groups was not statistically significant [34.6% (36/104) vs 25.0% (26/104), χ2=2.30, P=0.130]; according to the Clavien-Dindo classification of postoperative complications, the incidence of Clavien-Dindo grade Ⅲ complications in the group ≥80 years with diabetes mellitus were was higher than that in the group <80 years without diabetes [12.5% (13/104) vs 4.8% (5/104), χ2=3.89, P=0.049]. For local surgical complications, the incidence of postoperative anastomotic leak was significantly higher in the ≥80 years diabetic group than in the <80 years non-diabetic group ( χ2=4.70, P=0.030), and the incidence of postoperative wound infection was no statistical significance in the two group. For non-surgical local complications, there was a statistically significant difference in pulmonary infection in the ≥80 years diabetic group compared to the <80 non-diabetic group ( χ2=4.68, P=0.031) and in acute coronary syndrome ( χ2=4.02, P=0.045). Compared with the <80 years non-diabetic group, patients in the ≥80 years diabetic group had significantly longer postoperative hospital stay [(13.3±4.4)d vs (9.2±3.2) d, t=3.41, P=0.019]. The difference in adjuvant chemotherapy after surgery between the two groups was not statistically significant (67.3% vs 76.0%, χ2=1.92, P=0.166). The survival rate at 3 years after surgery was not statistically significant in both groups [68.9% vs 74.2%, χ2=4.34, P=0.085]. Conclusions:The short-term and long-term outcomes of colorectal cancer in advanced age with type 2 diabetes are satisfactory. Adequate preoperative assessment of the patient's physical condition should be carried out, close intraoperative control of blood glucose, and close postoperative monitoring and regulation of blood glucose should be performed, except for patients with severe comorbidities and coexisting diseases that cannot tolerate surgery and advanced tumours that have lost their surgical significance.