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.

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.

Research progress on the histopathological growth patterns of colorectal liver metastasis / 国际肿瘤学杂志

The histopathological growth patterns (HGPs) of colorectal cancer (CRC) liver metastasis reflect the complicated and varied interactions between tumor cells and host microenvironment. Exploring the tumor vascular and immunological features of HGPs, the relationship between HGPs and anti-tumor treatment efficacy, and HGPs prediction methods may have potential clinical aplication value for making optimal treatment strategies, evaluating patients' prognosis, and monitoring disease progression.

Effects of intervention in autophagy regulation of p62-Keap1/Nrf2-GPX4 pathway on ferroptosis and oxaliplatin resistance in colorectal cancer cells / 临床与实验病理学杂志

Purpose To investigate the effect of autophagy intervention on ferroptosis and drug resistance of colorectal canc-er cells and its molecular mechanism.Methods The human colorectal cancer cell lines HCT-8,COLO205,HCT-116,SW620,and SW480 were cultured.HCT-116 cells with moder-ate expression of LC3 were screened,and the expression differ-ences of LC3,p62,Keap1,Nrf2,GPX4 proteins,Fe2+,GSH,and MDA between them and OXA-resistant HCT-116/OXA cell lines were detected.The expression levels of LC3,p62,Keap1,Nrf2,GPX4,Fe2+,GSH and MDA were assessed in HCT-116/OXA cells through the intervention of autophagy and ferroptosis intervention agent combined with oxaliplatin.The proliferative activity and sensitivity to oxaliplatin in each group were detected by CCK-8 assay.Cell growth and invasion ability of each group were detected by plate cloning and Trans well assay.Results LC3,p62 and GPX4 expression levels of HCT-116 cells in the 5 groups were moderate.Compared with HCT-116 cells,HCT-116/OXA was less sensitive to oxaliplatin,and the proteins of p62,Nrf2 and GPX4 were highly expressed,LC3 and Keap1 were lowly expressed,and the expression of Fe2+,GSH and MDA were increased(P＜0.05).The levels of LC3,Keap1 protein,Fe2+and MDA in Rapa and Rapa+Fer-1 groups were higher than those in Fer-1 and control groups,while p62,Nrf2,GPX4 and GSH levels were lower.The expressions of GPX4 pro-tein and GSH in Rapa+Fer-1 group were lower than those in Rapa group(P＜0.05).In the autophagy inhibitor group,LC3,p62,Nrf2,GPX4 and GSH were highly expressed in the CQ and CQ+Erastin groups compared with the control and Eras-tin groups,while Keap1 protein,Fe2+and MDA were low.The levels of GPX4 protein and GSH in Erastin group were lower than those in the other three groups,and the levels of Fe2+and MDA were higher than those in the other three groups(P＜0.05).The combination of autophagy activator OXA showed that Rapa intervention group had higher chemical sensitivity to OXA,less number of migrating cells and lower cell proliferation activity than the other three groups.The sensitivity of Rapa+Fer-1 group to oxaliplatin was lower than that of Rapa group,but higher than that of Fer-1 group and control group(P＜0.05).There was no significant difference between Fer-1 group and con-trol group(P＜0.05).Compared with the control group,the cell activity,migration capacity and clonogenesis capacity of Erastin,CQ+Erastin and CQ groups were decreased when auto-phagy inhibitor was combined with OXA,and the Erastin group was the lowest,while the CQ+Erastin group was higher than the Erastin group,and lower than the CQ group(P＜0.05).Con-clusion In colorectal cancer,autophagy is involved in the regu-lation of ferroptosis,and intervention in autophagy can regulate ferroptosis in colorectal cancer cells through the p62-Keap1/Nrf2-GPX4 pathway,thereby reversing oxaliplatin resistance.

Effect of down-regulation of PPAPDC1A expression on proliferation,invasion and metastasis of colorectal cancer cells / 临床与实验病理学杂志

Purpose To investigate the expression and re-lationship of phosphatidic acid phosphatase 2 domain 1A(PPAPDC1A),also known as phospholipid phosphatase 4(PLPP4),in colorectal cancer(CRC)tissues and different colorectal cancer cells.Methods Immunohistochemical EnVi-sion method was applied to detect the expression of PPAPDC1A in 60 CRC tissues and paired paracancerous tissues.Stable over-expression and silencing cell lines of PPAPDC1A were success-fully constructed by gene transfection,and the effects of this gene on different colorectal cancer cell lines were investigated by CCK-8,Transwell,subcutaneous tumor formation in nude mice and tail vein injection in nude mice.Results PPAPDC1A ex-pression was upregulated in CRC tissues compared with paracan-cerous tissues,and the intensity of PPAPDC1A expression was negatively correlated with cell differentiation(P=0.011).PPAPDC1A stable overexpression and interference cell lines were successfully constructed.The results of in vitro and in vivo experiments showed that the growth rate(SW480-PPAPDC1A,RKO-PPAPDC1A groups:0.38±0.03,0.25±0.01),the number of cells crossing the compartment(SW480-PPAPDC1 A,RKO-PPAPDC1A groups:218.33±7.09,96.33±1.52),the number of clone formation(SW480-PPAPDC1 A,RKO-PPAP-DC1A groups:174.33±5.03,245.00±7.00),the in vivo tumor volume(4.16±0.91),and the number of lung metasta-sis in nude mice(5.1±3.84)were significantly higher in the PPAPDC1A stably overexpressing cell lines compared with the Vector group(P＜0.05).However,the growth rate(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:0.14±0.02,0.16±0.05),number of cells crossing the chambers(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:13.33±0.57,18.33±0.51),number of clone formation(SW620-shPPAP-DC1A,LOVO-shPPAPDC1A groups:28.33±1.52,8.67± 0.57),tumor volume(0.56±0.21),and number of lung me-tastasis in nude mice(1.2±1.03)were significantly lower(P＜0.05)in the PPAPDC1 A-silenced cell line compared with the NC group.Conclusion Down-regulation of PPAPDC1A expres-sion inhibits the proliferation,invasion,migration and metastatic ability of CRC cells.

Clinical significance of FOXA3 expression in colorectal cancer / 临床与实验病理学杂志

Purpose To analyze the expression of FOXA3 in colorectal cancer(CRC)and its correlation with clinicopatho-logical features.Methods FOXA3 mRNA expression in 31 CRC cancer tissues and their matched normal tissues was detec-ted by real-time quantitative PCR(RT-qPCR).The protein ex-pression of FOXA3 in 120 CRC cancer tissues was detected by immunohistochemical EnVision two-step method,and the clini-copathologic features such as lymph node metastasis and immu-nohistochemical expression were analyzed.Results The mRNA expression level of FOXA3 in colorectal cancer tissues was sig-nificantly higher than that in paired paracancer tissues(t=2.952,P=0.006 1).FOXA3 protein expression level in color-ectal cancer tissues was not significantly correlated with gender,age,site and size of patients,but significantly correlated with the degree of tissue differentiation(P=0.006)and lymph node metastasis(P=0.002).The degree of differentiation was nega-tively correlated with FOXA3 expression,while lymph node me-tastasis was positively correlated with FOXA3 expression.Sur-vival analysis showed that higher FOXA3 expression was associ-ated with worse overall survival(P＜0.000 1),and FOXA3 was an independent risk factor for prognosis in patients with colorectal cancer.Conclusion This study suggests that FOXA3 may play a promoting role in the occurrence and development of colorectal cancer,and FOXA3 may be a molecular marker for the diagnosis,metastasis and prognosis of colorectal cancer.

Gentianopsis paludosa xanthone combined with probiotics inhibits colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors / 天津医药

Objective To investigate the mechanism of Gentianopsis paludosa xanthone(GPX)combined with probiotics in the intervention of colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors.Methods Ninety rats were divided into the normal group,the model group[drinking sodium dextran sulfate(DSS)for 3 days]and the intervention group by random number table method.The model group was subdivided into the inflammatory stage group,the pre-inflammatory cancer group(DMH injection for 4 weeks),the intermediate inflammatory cancer group(DMH injection for 13 weeks)and the advanced inflammatory cancer group(DMH injection for 21 weeks).The administration group was subdivided into the groups(after the first day of drinking DSS,drugs for each group were given by gavage once a day for 8 weeks)on the basis of the advanced inflammatory cancer group,including the GPX group(GPX 69.3 mg/kg),the probiotic group,the combined group(GPX+probiotics 400 mg/kg)and the thalidomide group(thalidomide 13.5 mg/kg).The disease activity index(DAI),colon length and wet mass index were compared between all groups.Characteristics of colon tumors were observed,and pathological changes of colon were observed by HE staining.The expression levels of transforming growth factor(TGF)-β1,Smad4,Smad7,interleukin(IL)-6 and tumor necrosis factor(TNF)-α were detected by Western blot assay and enzyme-linked immunosorbent assay,respectively.Results Compared with the advanced inflammatory cancer group,the administration groups showed an increase in colon length,the expression levels of TGF-β1 and Smad4 protein,a decrease in colon wall thickness,wet mass index,maximum tumor diameter,the levels of Smad7,IL-6,TNF-α,and DAI score decreased in the GPX group and the combined group(P＜0.05).The structure and morphology of intestinal mucosa were improved in the GPX group,the probiotic group and the combination group,and the structure of colonic crypt and goblet cell number were increased.Compared with the probiotic group and the GPX group,the colon wall thickness,colon wet mass index and tumor number were decreased,the protein expression levels of TGF-β1 and Smad4 were increased,and levels of IL-6 and TNF-α were decreased in the combination group(P＜0.05).Conclusion GPX combined with probiotics could inhibit the transformation of colon inflammation-tumor,and the mechanism may be related to the regulation of TGF-β1/Smads pathway and the inhibition of pro-inflammatory factors of IL-6 and TNF-α.

Risk factors for prolonged postoperative ileus after radical colorectal cancer resection / 中华普通外科杂志

Objective:To investigate the prognostic factors for the risk of prolonged postoperative ileus (PPOI) after colorectal cancer resection.Methods:The clinical data of 896 patients undergoing radical colorectal cancer resection at Affiliated Hospital of Qingdao University between Jan 2016 and Dec 2022 were retrospectively analyzed. Patients were divided into PPOI group (59 cases) and non-PPOI group (837 cases) according to whether PPOI happened after surgery. Potential prognostic factors for the risk of developing PPOI were analyzed by univariate and multivariate Logistic regression. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:Fifty-nine patients (6.5%) developed PPOI after radical colorectal cancer resection. Univariate and multifactorial logistic regression analyses showed that diabetes mellitus ( OR=2.360, P=0.018), preoperative albumin level <35 g/L ( OR=2.196, P=0.036), postoperative epidural analgesia ( OR=2.399, P=0.007), open surgery ( OR=3.413, P=0.001), and ICU hospitalization ≥ 48 h ( OR=6.134, P<0.001) were independent prognostic factors for PPOI. Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.806 (95% CI: 0.698-0.838), with an accuracy, sensitivity and specificity of 73.9%, 74.0%, 72.9%, respectively. Conclusion:Diabetes mellitus, preoperative albumin level, postoperative epidural analgesia, open surgery, and ICU hospitalization ≥ 48 h were risk factors for PPOI after radical colorectal cancer resection.

Salvage radical surgery in early-stage colorectal cancer patients undergoing non-curative endoscopic resection / 中华普通外科杂志

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Impact of colorectal cancer on skeletal muscle atrophy in patients with and without obesity / 中华普通外科杂志

Objective:To explore whether the degree of skeletal muscle atrophy in obese individuals under the influence of colorectal cancer is more severe than that in non-obese individuals.Methods:The clinical data of patients who underwent radical resection of colorectal cancer in our department from Jul 2020 to Dec 2021 was collected. Sixty-four obese patients were included and 64 non-obese patients were matched according to propensity score. At the same time, 51 obese patients were collected from non-tumor patients and matched with 51 non-obese patients. The psoas muscle index (PMI) of included patients was analyzed and compared.Results:The PMI of patients with colorectal cancer was significantly lower than that of corresponding non-tumor patients, regardless of gender and body weight (both P<0.05). The PMI of obese patients with colorectal cancer was significantly lower than that of non-obese patients ( P<0.05). Conclusions:The impact of colorectal cancer on skeletal muscle atrophy in obese individuals is greater than that in normal weight individuals. Therefore, the skeletal muscle status of obese patients with colorectal cancer should be evaluated more comprehensively.

Clinical application value of serum exosomal circRPS6 in the diagnosis and prognosis assessment of patients with colorectal cancer / 中华检验医学杂志

Objective:To investigate the expression and clinical application value of exosomal circRPS6 in serum of colorectal cancer (CRC) patients.Methods:Peripheral serum samples were collected from 115 CRC patients admitted to Henan Provincial People′s Hospital from January 2019 to December 2020. There were 68 males and 47 females, aged (63.0±9.5) years. Meanwhile, one hundred and twenty healthy subjects from the same period wereenrolled, with 70 males and 50 females, aged (61.0±10.7) years. In addition, sixty pairs of tumor and adjacent tissue specimens from CRC patients undergoing surgical treatment were collected. The circRPS6 expression in serum exosome and tissue of CRC patients were detected via real-time fluorescence quantitative PCR (RT-qPCR), and its relationship with clinicopathological features and prognosis of CRC patients were also investigated. The levels of CEA and CA19-9 in serum were detected by electrochemiluminescence assay. The ROC curve and AUC were used to estimate the diagnostic capacity. Univariate and multivariate regression analysis was performed using Cox proportional hazard analysis.Results:The expression level of circRPS6 in CRC tissue was significantly higher than that in adjacent tissue( Z=5.38, P<0.001). Compared with healthy control, the expression of serum exosomal circRPS6 was significantly upregulated in the CRC group( t=14.52, P<0.001). ROC curve analysis results showed that the AUC of exosomal circRPS6 was 0.882, which had a higher diagnostic efficacy in CRC patients than CEA and CA19-9 detection. There was a positive correlation between the expression level of exosomal circRPS6 with TNM stage and lymph node metastasis and distant metastasis( P<0.05). Kaplan-Meier survival analysis revealed that CRC patients with low exosomal circRPS6 levels had a much longer average survival time compared with those in high group. Moreover,multivariate analysis results indicated that exosomal circRPS6 was an independent prognostic factor in colorectal cancer. Conclusion:Exosomal circRPS6 is highly expressed in the serum of CRC patients and correlated with malignant progression and poor prognosis, which is expected to be a potential marker for the diagnosis and prognosis evaluation of CRC patients.

Gut microbiota aids in differentiating proximal colorectal cancer in the combination of tumor markers / 中华检验医学杂志

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

Study on the mechanism of herb cake-partitioned moxibustion inhibiting tumor growth in colitis-associated colorectal cancer based on KDM4D receptor / 针灸推拿医学（英文版）

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

Expressions and clinical significances of histone marks H3K9me3 and H3K27me3 in colorectal cancer patients / 肿瘤研究与临床

Objective:To investigate the expressions and clinical significances of histone marks H3K9me3 and H3K27me3 in colorectal cancer.Methods:A retrospective case-control study was conducted. The clinical data of 98 patients with colorectal cancer in Shanxi Province Cancer Hospital from May 2008 to July 2017 were retrospectively analyzed, including 35 patients in the non-metastatic operation-only group, 29 patients in the synchronous hepatic oligometastasis group and 34 patients in the extensive metastasis group, and 33 patients with benign colorectal lesions who underwent colonoscopy in 2017 were selected as the control group. Immunohistochemical assay was used to detect the expressions of H3K9me3 and H3K27me3 proteins in each group, and the expressions of H3K9me3 and H3K27me3 proteins in colorectal cancer patients with different clinicopathological features were analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was performed.Results:The positive expression rate of H3K9me3 protein in colorectal cancer group was 11.2% (11/98), which was lower than that in control group [60.6% (22/33)] ( χ2 = 33.33, P < 0.001); the positive expression rate of H3K27me3 protein in colorectal cancer group was 10.6% (13/98), which was lower than that in control group [97.0% (32/33)] ( χ2 = 76.70, P < 0.001). The positive expression rates of H3K9me3 protein were 60.6% (20/33), 17.1% (6/35), 10.3% (3/29) and 5.9 % (2/34) in the control group, the non-metastatic operation-only group, the synchronous hepatic oligometastasis group and the extensive metastasis group, respectively, and the difference was statistically significant ( χ2 = 26.10, P < 0.001); the positive expression rates of H3K27me3 protein were 97.0% (32/33), 14.3% (5/35), 20.7% (6/29) and 5.9% (2/34), respectively, and the difference was statistically significant ( χ2 = 44.16, P < 0.001). The positive expression rate of H3K27me3 in colorectal cancer tissues of patients with lymph node metastasis degree ≤0.2 was higher than that of patients with lymph node metastasis degree >0.2 [22.4% (11/49) vs. 4.2% (2/48), χ2 = 6.98, P = 0.008]. The median overall survival (OS) time of H3K9me3 positive and negative colorectal cancer patients was 77.0 months (95% CI: 10.6-143.3 months) and 34.0 months (95% CI: 25.5-42.5 months), respectively, and there was no significant difference in OS between the two groups ( P = 0.078). The median OS time of H3K27me3 positive and negative colorectal cancer patients was 39.0 months (95% CI: 15.3- 62.7 months) and 34.0 months (95% CI: 24.3-43.7 months), respectively, and there was no significant difference in OS between the two groups ( P = 0.524). Conclusions:The expressions of H3K9me3 and H3K27me3 in colorectal cancer tissues are lower than those in colorectal benign lesions, and gradually decrease with occurrence of liver metastasis and extensive metastasis. H3K9me3 and H3K27me3 may be potential cancer suppressor factors.

Analysis of clinical features and prognosis of simultaneous double primary and single primary colorectal cancer patients / 肿瘤研究与临床

Objective:To explore the clinical features and prognosis of simultaneous double primary and single primary colorectal cancer patients.Methods:A retrospective case series study was conducted. The clinical data of 45 patients with simultaneous double primary colorectal cancer, 53 patients with single primary colon cancer and 59 patients with single primary rectal cancer in Shanxi Province Cancer Hospital from January 2015 to January 2018 were retrospectively analyzed, including gender, age, drinking history, smoking history, body mass index (BMI), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), hemoglobin, albumin, TNM stage. The clinicopathological characteristics of the three groups were compared. Survival analysis was performed using the Kaplan-Meier method to compare the overall survival of the three groups.Results:The age of simultaneous double primary colorectal cancer patients was (63±11) years old, including 28 males and 17 females; the age of single primary colon cancer patients was (61±12) years old, including 30 males and 23 females; the age of single primary rectal cancer patients was (60±11) years old, including 30 males and 29 females. There was a significant difference in BMI between patients with double primary cancer and single primary colon cancer ( P = 0.041), but there were no significant differences in gender, age, drinking history, smoking history, CEA, CA199, hemoglobin, albumin and TNM stage (all P > 0.05). There were significant differences in BMI, CEA and CA199 between patients with double primary cancer and single primary rectal cancer (all P < 0.05), but there were no significant differences in gender, age, drinking history, smoking history, hemoglobin, albumin and TNM stage (all P > 0.05). The 1-, 3- and 5-year overall survival rates of the double primary cancer patients were 95.56%, 77.78% and 62.22%, the single primary colon cancer patients were 94.34%, 81.13% and 69.81%, and the single primary rectal cancer patients were 100.00%, 88.14% and 72.88%, respectively. There was no significant difference in OS among patients with double primary cancer, single primary rectal cancer and single primary rectal cancer (both P > 0.05). Conclusions:Abnormally elevated BMI may be associated with the risk of developing simultaneous double primary colorectal cancer. Detection of CEA and CA199 is helpful in monitoring rectal cancer patients for the combination of other primary tumors. The prognosis of patients with single primary colon or rectal cancer is comparable to that of patients with simultaneous double primary colorectal cancer.

Progress of poly (ADP-ribose) polymerase inhibitors in treatment of colorectal cancer / 肿瘤研究与临床

Colorectal cancer is a highly malignant disease characterized by a poor prognosis. Although the targeted therapy based on chemotherapy improves the efficacy, the prognosis of advanced colorectal cancer patients is poor. Poly (ADP-ribose) polymerase (PARP) inhibitors, which act through a synergistic lethal mechanism, have been widely utilized in treating ovarian and breast cancer cases with homologous recombination deficiency and have demonstrated positive clinical outcomes. Recently, due to advancements in next-generation sequencing technology and the development of precision targeted therapy, an increasing number of clinical trials have started to investigate the potential of PARP inhibitors in colorectal cancer treatment. This review summarized the molecular mechanism of PARP inhibitors in the treatment of colorectal cancer and the application of several combined PARP inhibitors therapy regimens in colorectal cancer, in order to provide new insights for the treatment of colorectal cancer.

Progress of gastrointestinal endoscopy linked color imaging in colorectal cancer screening / 肿瘤研究与临床

Colonoscopy is an important diagnostic tool for colorectal cancer. Traditional white light endoscopy has a high underdiagnosis rate, and linked color imaging (LCI) as a kind of image-enhanced endoscopy can effectively improve the detection of early colorectal cancer. LCI can improve the detection of adenoma, and it contributes to the detection and evaluation of sessile serrated lesions, ulcerative colitis and Lynch syndrome lesions. In addition, LCI combined with staining and artificial intelligence can predict the histopathologic type and invasion depth of colorectal lesions, and guide the selection of treatment. This paper reviews the characteristics of LCI and progress of its application in colorectal cancer screening.

Impact of cancer-associated fibroblasts on immunotherapy and liver metastasis in colorectal cancer / 临床肝胆病杂志

ObjectiveTo investigate the impact of cancer-associated fibroblasts （CAFs） on immunotherapy and liver metastasis in colorectal cancer （CRC）. MethodsThe single-cell sequencing data （GSE205506） of CRC patients with mismatch repair deficiency （MMRd） were downloaded from the gene expression omnibus database， and R software was used to preprocess the original sequencing data and establish the umap of fibroblast subpopulations， with each subpopulation named based on signature genes. GraphPad was used for the statistical analysis of the proportion of each fibroblast subpopulation， and the key subpopulations with significant differences were analyzed among CRC patients before and after PD-1 immunotherapy， as well as between the patients with pathological complete response （pCR） and those without pCR （non-pCR） after treatment. The analysis of differentially expressed genes and the gene pathway enrichment analysis were performed for the key subpopulations. The TCGA database was used to perform a prognostic and survival analysis of the signature genes of key CAF subpopulations， and RNA sequencing data were used to score and calculate the proportion of key CAF subpopulations in the primary lesions of CRC patients with liver metastasis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Kaplan-Meier method was used to plot survival curves， and the log-rank test was used to calculate survival rates. CellPhoneDB software was used to analyze the receptor-ligand interaction between fibroblast subpopulations and tumor cells， and in vitro cell experiments were used to validate the effect of NRG1， a key ligand molecule， on the migration and invasion abilities of CRC cells. ResultsAfter PD-1 immunotherapy for CRC patients， there was a significant reduction in the proportion of F6_MMP1+CAFs （P<0.001）， which was only observed in patients achieving complete remission after immunotherapy. F6_MMP1+CAFs were upregulated， as well as the genes and signaling pathways associated with tumor migration and invasion， and in addition， there was a significant increase in F6_MMP1+CAFs in the tumor tissue of CRC patients with liver metastasis （P<0.000 1）. As a ligand， NRG1 expressed by F6_MMP1+CAFs interacted with ERBB3 receptor expressed by tumor cells， and the in vitro experiments confirmed that NRG1 promoted the migration and invasion abilities of tumor cells by activating the ERBB signaling pathway （P<0.05）. ConclusionF6_MMP1+CAFs may affect the efficacy of PD-1 immunotherapy in CRC patients and play an important role in promoting liver metastasis in CRC. F6_MMP1+CAFs， along with NRG1 that is produced by them and can promote tumor metastasis， can be used as potential therapeutic targets and prognostic markers for CRC.

Apparent diffusion coefficient for evaluating short-term efficacy of TACE for treating colorectal cancer liver metastases / 中国介入影像与治疗学

Objective To observe the value of apparent diffusion coefficient(ADC)for evaluating short-term efficacy of TACE for treating colorectal cancer liver metastases(CRLM).Methods Data of 60 liver metastases in 28 CRLM patients who underwent TACE were retrospectively analyzed.Based on MRI after the first TACE,according to the response evaluation criteria of solid tumors,the liver metastases were divided into response group(n=38)and non-response group(n=22).ADC parameters obtained with diffusion weighted imaging(DWI)before and after TACE,including ADC before TACE(ADCpre),after the first TACE(ADCpost1)and after the second TACE(ADCpost2)were compared between groups,while ADC change value(ΔADC)and the percentage of ΔADC were calculated.The maximum diameter of the target foci were measured,and the correlation between ΔADCpost1 and the change of the maximum diameter of target foci were analyzed.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to observe the efficacy of ΔADCpost1 for evaluating short-term efficacy of TACE for CRLM.Results No significant difference of ADCpre was found between groups(P=0.484).After the first TACE,ADCpost1,ΔADCpost1 and percentage of ΔADCpost1 in response group were all higher than those in non-response group(all P＜0.05).After the second TACE,no significant difference of ADCpost2,ΔADCpost2 nor percentage of ΔADCpost2 was found between groups(all P＞0.05).The maximum diameter change of the target foci after the first TACE was(-0.48±0.93)cm,which was negatively correlated with ΔADCpost1(rs=-0.347,P=0.007).AUC of ΔADCpost1 for evaluating short-term efficacy of TACE for CRLM was 0.717.Conclusion ADC had good efficacy for evaluating short-term efficacy of TACE for treating CRLM.