Prótesis colónicas en el tratamiento paliativo del cáncer colónico. Nuestra evaluación tras 10 años de experiencia / Self-expanding metal stents in the palliative treatmentof coloncancer. Results of 10 years of experience

Introducción: la colocación de prótesis metálicas autoexpansibles (PAE) por vía endoscópica surge como opción terapéutica para la obstrucción colónica neoplásica en dos situaciones: como tratamiento paliativo y como puente a la cirugía curativa. Este procedimiento evita cirugías en dos tiempos y disminuye la probabilidad de colostomía definitiva y sus complicaciones con el consecuente deterioro de la calidad de vida. Objetivo: comunicar nuestra experiencia en la colocación de PAE para el tratamiento paliativo de la obstrucción colorrectal neoplásica. Diseño: retrospectivo, longitudinal, descriptivo y observacional. Material y métodos: se incluyeron todos los pacientes a quienes el mismo grupo de endoscopistas les colocó PAE con intención paliativa por cáncer colorrectal avanzado entre agosto de 2008 y diciembre de 2019. Fueron analizadas las variables demográficas y clínicas, el éxito técnico y clínico, las complicaciones tempranas y tardías y la supervivencia. Resultados: se colocó PAE en 54 pacientes. La media de edad fue 71 años. El 85% de las lesiones se localizó en el colon izquierdo. En el 57% de los pacientes se realizó en forma ambulatoria. El éxito técnico y clínico fue del 92 y 90%, respectivamente y la supervivencia media de 209 días. La tasa de complicaciones fue del 29,6%, incluyendo un 14,8% de obstrucción y un 5,6% de migración. La mortalidad tardía atribuible al procedimiento fue del 5,6%, ocasionada por 3 perforaciones tardías: 2 abiertas y 1 microperforación con formación de absceso localizado. Conclusiones: la colocación de PAE como tratamiento paliativo de la obstrucción neoplásica colónica es factible, eficaz y segura. Permitió el manejo ambulatorio o con internación breve y la realimentación temprana, mejorando las condiciones para afrontar un eventual tratamiento quimioterápico paliativo. Las mayoría de las complicaciones fueron tardías y resueltas endoscópicamente en forma ambulatoria. (AU)

Introduction: endoscopic placement of self-expanding metal stents (SEMS) emerges as a therapeutic option for neoplastic obstruction of the colon in two situations: as palliative treatment and as a bridge to curative surgery. This procedure avoids two-stage surgeries and reduces the probability of permanent colostomy and its complications with the consequent deterioration in quality of life. Objective: to report our experience in the placement of SEMS as palliative treatment in neoplastic colorectal obstruction. Design: retrospective, longitudinal, descriptive and observational study. Methods: all patients in whom the same group of endoscopists performed SEMS placement with palliative intent for advanced colorectal cancer between August 2008 and December 2019 were analyzed. Data collected were demographic and clinical variables, technical and clinical success, early and late complications, and survival. Results: SEMS were placed in 54 patients. The average age was 71 years. Eighty-five percent were left-sided tumors. In 57% of the patients the procedure was performed on an outpatient basis. Technical and clinical success was 92 and 90%, respectively, and median survival was 209 days. The complication rate was 29.6%, including 14.8% obstruction and 5.6% migration. Late mortality attributable to the procedure was 5.6%, caused by 3 late perforations: 2 open and 1 microperforation with localized abscess formation. Conclusions: The placement of SEMS as a palliative treatment for neoplastic colonic obstruction is feasible, effective and safe. It allowed outpa-tient management or brief hospitalization and early refeeding, improving the conditions to face an eventual palliative chemotherapy treatment. Most complications were late and resolved endoscopically on an outpatient basis. (AU)

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

Identification of potential urinary protein biomarkers in colorectal cancer: a pilot study using a proteomic approach

Colorectal cancer (CRC) is among the most diagnosed malignancies worldwide, and it is also the second leading cause of cancer-related deaths. Despite recent progress in screening programs, noninvasive accurate biomarkers are still needed in the CRC field. In this study, we evaluated and compared the urinary proteomic profiles of patients with colorectal adenocarcinoma and patients without cancer, aiming to identify potential biomarker proteins. Urine samples were collected from 9 patients with CRC and 9 patients with normal colonoscopy results. Mass spectrometry (label-free LC—MS/MS) was used to characterize the proteomic profile of the groups. Ten proteins that were differentially regulated were identified between patients in the experimental group and in the control group, with statistical significance with a p value ≤ 0.05. The only protein that presented upregulation in the CRC group was beta-2-microglobulin (B2M). Subsequent studies are needed to evaluate patients through different analysis approaches to independently verify and validate these biomarker candidates in a larger cohort sample. (AU)

Prognostic roles and survival benefits of endoscopic resection versus surgical resection in the management of malignant colon polyps

Background: Due to few sufficient data regarding the comparison between endoscopic and surgical resection of malignant colorectal polyps regarding outcomes and survival benefits, there are no clear guidelines of management strategies of malignant colorectal polyps. The aims of the present study were to compare endoscopic resection alone and surgical resection in patients with malignant polyps in the colon (T1N0M0) readings advantages, disadvantages, recurrence risks, survival benefits, and long-term prognosis to detect how management strategy affects outcome. Patients and methods: we included 350 patients. All included patients were divided into 2 groups; the first group included 100 patients who underwent only endoscopic polypectomy and the second group included 250 patients who underwent endoscopic polypectomy followed by definitive surgical resection after histopathological diagnosis. We followed all patients for about 5 years, ranging from 18 to 55 months. The primarily evaluated parameters are surgical consequences and patients' morbidity. The secondary evaluated parameters are recurrence risks, recurrence free survival, and overall survival rates. Results: The age of patients who underwent polypectomy is usually younger than the surgical group, males have more liability to polypectomy in comparison with females. Patients with tumors in the left colon have more liability to polypectomy in comparison with the right colon (p< 0.0001). Tumor factors associated with more liability to surgical resection are presence of lymphovascular invasion, high grade, and poor tumor differentiation (p< 0.0001). The management strategy was the most significant predictor of overall and recurrence free survival rates in patients with malignant colon polyps (p< 0.001). Conclusions: We found that survival benefits and lower incidence of recurrence are detected in the surgical resection group more than in the polypectomy group. (AU)

Risk factors and outcomes of occurrence of anastomotic leakage and reoperations for its management after colorectal surgery

Background: Anastomotic leakage (AL) is still the most annoying postsurgery complication after colorectal resection due to its serious complications up to death. Limited data were available regarding differences in AL incidence, management, and consequences for different types of colorectal resection. The aim of the present work was to evaluate differences in incidence of AL, incidence of postoperative complications, and length of hospital stay in a large number of patients who underwent elective colorectal resection for management of colorectal lesions. In addition to detect when and what type of reoperation for management of AL occur after colorectal resection. Patients: All 250 included patients underwent elective surgeries for colorectal resection with performance of primary anastomosis for management of colorectal neoplastic and non-neoplastic diseases in the period between May 2016 and July 31, 2021. We followed the patients for 90 days; we registered the follow-up findings. Results: the rates of AL occurrence were variable after the different procedures. The lowest rate of AL occurrence was found in patients who underwent right hemicolectomy, then in patients who underwent sigmoidectomy, left hemicolectomy, transversectomy and anterior resection (p= 0.004). A stoma was frequently performed during reoperation (79.5%) which was significantly different between different procedures: 65.5% in right hemicolectomy, 75.0% in transversectomy, 85.7% in left hemicolectomy, and 93.0% in sigmoid resection (p< 0.001). Conclusion Rates, types, time of occurrence and severity of AL vary according to the type of colectomy performed and selective construction of stoma during AL reoperation is currently safely applied with comparable mortality rates for patients who did and who did not have a stoma after reoperation. (AU)

Fulminant endogenous panophthalmitis caused by Clostridium septicum infection / Panoftalmite endógena fulminante por infecção por Clostridium septicum

ABSTRACT We report an unusual case of fulminant endogenous Clostridium septicum panophthalmitis. A 74-year-old male patient presented with sudden amaurosis in the right eye, which in a few hours, evolved into an orbital cellulitis, endophthalmitis, anterior segment ischemia, and secondary perforation of the eye. A complete diagnostic study, which included cranial and orbital contrast-enhanced computed tomography scan, contrast-enhanced magnetic resonance imaging, blood cultures, and complete blood work, were performed. No causal agent was identified. Clostridium septicum infection caused fulminant gaseous panophthalmitis. Despite broad-spectrum antibiotic treatment, evisceration of the eyeball was necessary. The extension study showed a colon adenocarcinoma as the origin of the infection. Clostridium septicum panophthalmitis is a rare but aggressive orbital infection. This infection warrants the identification of a neoplastic process in the gastrointestinal tract in many cases not previously described.

RESUMO Este é o relato de um caso incomum de panoftalmite endógena fulminante por Clostridium septicum. Um paciente do sexo masculino, 74 anos, apresentou amaurose súbita no olho direito, que em poucas horas evoluiu para celulite orbitária, endoftalmite, isquemia do segmento anterior e perfuração secundária do olho. Foi realizado um estudo diagnóstico completo, que incluiu uma tomografia computadorizada com contraste cranial e orbital, um exame de ressonância magnética, hemocultura e hemograma completo. Nenhum agente causal foi identificado. A infecção por Clostridium septicum causou uma panoftalmite gasosa fulminante. Apesar do tratamento com antibióticos de amplo espectro, foi necessário eviscerar o globo ocular. O estudo de seguimento mostrou um adenocarcinoma de cólon como a origem da infecção. A panoftalmite por Clostridium septicum é um tipo raro, mas muito agressivo de infecção orbitária. Essa infecção deve sugerir a busca por um processo neoplásico no trato gastrointestinal, em muitos casos não diagnosticado anteriormente.

Self-Management Program in Adults with Colorectal Cancer: A Pilot Study / Programa de automanejo en adultos con cáncer colorrectal: estudio piloto / Programa de autogestão em adultos com câncer colorretal: estudo-piloto

Objective: To design and validate a nursing intervention and its effect on improving self-management behaviors in patients with colorectal cancer following surgery within eight weeks after discharge. Method: Pilot study using Sidane and Braden's intervention design proposal, which included determining the guiding theoretical model, characterization of the intervention, validation with eight experts through content validity, and a pilot test with ten patients during the second semester of 2020. Results: The intervention obtained, called the Program for Self-Management Training in Colorectal Cancer (PEACCR, by its acronym in Spanish), is based on the theory of individual and family self-management in the dimensions proposed by Ryan and Sawin. The validity with experts indicates that it meets the criteria of clarity, precision, comprehension, relevance, and pertinence. The pilot reports an increase in self-management behaviors and the dimensions of knowledge, coping, and health personnel-patient alliance in months 1 and 2, with statistical significance. Conclusions: The designed and validated intervention increases the self-management behaviors of patients with colorectal cancer. The proposed scheme is highly acceptable to participants.

Objetivo: diseñar y validar una intervención de enfermería y su efecto para mejorar los comportamientos de automanejo en pacientes con cáncer colorrectal, después de una intervención quirúrgica dentro de las ocho semanas posteriores al alta. Método: estudio piloto que acoge la propuesta de diseño de intervenciones de Sidane y Braden, lo que incluyó determinar el modelo teórico orientador, la caracterización de la intervención, la validación con ocho expertos a través de la validez de contenido, y una prueba piloto con diez pacientes, durante el segundo semestre del año 2020. Resultados: la intervención obtenida, denominada Programa para el Entrenamiento en Automanejo en Cáncer Colorrectal (PEACCR), se basa en la teoría de automanejo individual y familiar en las dimensiones planteadas por Ryan y Sawin. La validez con expertos indica que cumple con los criterios de claridad, precisión, comprensión, relevancia y pertinencia. El piloto reporta un aumento en los comportamientos de automanejo y en las dimensiones de conocimiento, afrontamiento y alianza personal de salud-paciente en el mes 1 y en el mes 2, con significancia estadística. Conclusiones: la intervención diseñada y validada aumenta los comportamientos de automanejo de pacientes con cáncer colorrectal. El esquema propuesto es de alta aceptabilidad para los participantes.

Objetivo: desenhar e validar uma intervenção de enfermagem e seu efeito para melhorar os comportamentos de autogestão em pacientes com câncer colorretal, depois de uma intervenção cirúrgica dentro das oito semanas posteriores à alta. Materiais e método: estudo-piloto que utiliza a proposta de desenho de intervenções de Sidane e Braden, o que inclui determinar o modelo teórico orientador, a caracterização da intervenção, a validação com oitos especialistas por meio da validade de conteúdo e um teste-piloto com dez pacientes, durante o segundo semestre de 2020. Resultados: a intervenção obtida, denominada "Programa para o Treinamento em Autogestão em Câncer Colorretal", está baseada na teoria de autogestão individual e familiar nas dimensões propostas por Ryan e Sawin. A validade com especialistas indica que cumpre com os critérios de clareza, precisão, compreensão, relevância e pertinência. O piloto relata um aumento nos comportamentos de autogestão e nas dimensões de conhecimento, enfrentamento e parceria pessoal de saúde-paciente no mês 1 e no mês 2, com significância estatística. Conclusões: a intervenção desenhada e validada aumenta os comportamentos de autogestão de pacientes com câncer colorretal. O esquema proposto é de alta aceitabilidade para os participantes.

Pode o Blue Laser Imaging colaborar no diagnóstico diferencial entre lesões neoplásicas e não neoplásicas colorretais? / Can Blue Laser Imaging collaborate in the differential diagnosis between neoplastic and non-neoplastic colorectal lesions?

Introdução: Imagem endoscópica aprimorada permite o diagnóstico diferencial das lesões colorretais em tempo real através do estudo da microvasculatura. Objetivo: Revisar o uso do Blue Laser Imaging (BLI) na análise do padrão dos capilares para o diagnóstico diferencial entre lesões neoplásicas e não neoplásicas. Métodos: Esta é revisão integrativa da literatura que colheu informações publicadas em plataformas virtuais em português e inglês. A busca para leitura e análise foi realizada nas plataformas SciELO ­ Scientific Electronic Library Online, Google Scholar, Pubmed e Scopus. Os descritores retirados do DeCS/MESH foram: "Blue laser imaging. Endoscopia. Cromoendoscopia, Pólipos colorretais. Magnificação" e seus correspondentes em inglês "Blue laser imaging. Image-enhanced endoscopy. Chromoendoscopy. Colorectal polyps. Magnification" com busca AND ou OR, considerando o título e/ou resumo. Foram incluídos somente os que tivessem maior correlação ao tema, e neles foi baseada a revisão com leitura, na íntegra, dos textos. Resultados: Ao final resultaram 22 artigos que compuseram esta revisão. Conclusão: BLI associada à magnificação mostrou bons resultados no diagnóstico histológico preditivo em tempo real para as lesões de cólon e reto.

Introduction: Improved endoscopic imaging allows the differential diagnosis of colorectal lesions in real time through the study of the microvasculature. Objective: To review the use of Blue Laser Imaging (BLI) in analyzing the capillary patern for the differential diagnosis between neoplastic and nonneoplastic lesions. Methods: This is an integrative review of the literature that collected information published on virtual platforms in Portuguese and English. The search for reading and analysis was carried out on the SciELO ­ Scientific Electronic Library Online, Google Scholar, Pubmed and Scopus platforms. The descriptors taken from DeCS/MESH were: "Blue laser imaging. Endoscopy. Chromoendoscopy, Colorectal polyps. Magnification" and its English counterparts "Blue laser imaging. Image-enhanced endoscopy. Chromoendoscopy. Colorectal polyps. Magnification" with AND or OR search, considering the title and/or abstract. Only those that had the greatest correlation to the topic were included, and the review was based on them, with reading, in full, of the texts. Results: In the end, 22 articles resulted that made up this review. Conclusion: BLI associated with magnification showed good results in real-time predictive histological diagnosis for colon and rectal lesions.

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

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

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

Modelo didáctico formativo del cirujano general para la atención del paciente con cáncer de colon / Didactic training model of the general surgeon for the care of patients with colon cancer

Fundamento: en la actualidad se observan restricciones epistemológicas y praxiológicas en la formación del residente de Cirugía General. La lógica hermenéutico-dialéctica de dicha formación se expresa en su relación con la práctica quirúrgica contextual; el desarrollo de las habilidades quirúrgicas discurre mediante la educación en el trabajo. Objetivo: diseñar un modelo didáctico de la formación quirúrgico-asistencial en la educación en el trabajo del residente de Cirugía General, para la atención integral de pacientes con cáncer de colon. Métodos: se realizó una investigación de desarrollo en el los hospitales "Saturnino Lora" y "Juan B. Zayas" de Santiago de Cuba durante 2021. Se emplearon métodos teóricos: análisis-síntesis, sistematización y generalización de experiencias, holístico-dialéctico, modelación y enfoque hermenéutico; empíricos: encuesta y entrevista a residentes, especialistas y expertos de ambos hospitales. Resultados: el modelo diseñado se sustenta en la sistematización y generalización de las experiencias de los autores concernientes a los períodos preoperatorio, operatorio y posoperatorio de la cirugía de esta neoplasia. Conclusiones: el modelo didáctico fue validado por expertos como pertinente, factible y aplicable; tiene como contradicción la relación entre la lógica secuencial algorítmica de la práctica quirúrgica y la lógica hermenéutico-dialéctica del proceso de formación del residente en Cirugía General, a fin de contribuir a disminuir las insuficiencias y limitaciones de este profesional durante el proceso formativo.

Background: currently epistemological and praxiological restrictions are observed in the training of the General Surgery resident. The hermeneutic-dialectical logic of such training is expressed in its relationship with contextual surgical practice; the development of surgical skills proceeds through the in-service training. Objective: to design a didactic model of surgical-care training in the in-service training of the General Surgery resident, for the comprehensive care of patients with colon cancer. Methods: a development investigation was carried out in the "Saturnino Lora" and "Juan B. Zayas" hospitals in Santiago de Cuba during 2021. Theoretical methods were used: analysis-synthesis, systematization and generalization of experiences, holistic-dialectical, modeling and hermeneutic approach; empirical ones: survey and interview with residents, specialists and experts from both hospitals. Results: the designed model is based on the systematization and generalization of the authors' experiences concerning the preoperative, operative, and postoperative periods of surgery for this neoplasm. Conclusions: the didactic model was validated by experts as pertinent, feasible and applicable; Its contradiction is the relationship between the algorithmic sequential logic of surgical practice and the hermeneutic-dialectical logic of the training process of the resident in General Surgery, in order to help reduce the insufficiencies and limitations of this professional during the training process.

Silenced ANP32A inhibits the growth, invasion and migration of colorectal cancer in vitro via the inactivation of AKT pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of ANP32A silencing on invasion and migration of colon cancer cells and the influence of the activity of AKT signaling pathway on this effect.@*METHODS@#Colorectal cancer HCT116 and SW480 were transfected with a small interfering RNA targeting ANP32A via a lentiviral vector. At 24, 48 and 72 h after the transfection, the changes in cell proliferation and AKT activity in the cells were detected using MTT assay and Western blotting, respectively. HCT116 and SW480 cells were treated with the AKT agonist SC79 or its inhibitor MK2206 for 24, 48, 72 and 96 h, and the changes in cell migration and invasion ability were analyzed using Transwell chamber assay and cell proliferation was assessed using MTT assay. The effects of SC79 and MK2206 on migration and invasion abilities of HCT116 and SW480 cells with or without ANP32A silencing were examined using wound healing and Transwell chamber assays, and the changes in the expression of metadherin (MTDH), a factor associated with cells invasion and migration, was detected with Western blotting.@*RESULTS@#Lentivirus-mediated ANP32A silencing significantly down-regulated the activity of AKT and inhibited the proliferation of both HCT116 and SW480 cells (P < 0.01). The application of AKT inhibitor MK2206 obviously inhibited the proliferation, invasion and migration of the colorectal cancer cells (P < 0.05), while the AKT agonist SC79 significantly promoted the invasion and migration of the cells (P < 0.01). In HCT116 and SW480 cells with ANP32A silencing, treatment with MK2206 strongly enhanced the inhibitory effects of ANP32A silencing on cell invasion and migration (P < 0.05) and the expression of MTDH, while SC79 partially reversed these inhibitory effects (P < 0.01).@*CONCLUSION@#ANP32A silencing inhibits invasion and migration of colorectal cancer cells possibly by inhibiting the activation of the AKT signaling pathway.

Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.

Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer / 中国中药杂志

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology.@*METHODS@#TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice.@*RESULTS@#Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05).@*CONCLUSION@#LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.

NKD1 promotes glucose uptake in colon cancer cells by activating YWHAE transcription / 南方医科大学学报

OBJECTIVE@#Bo investigate the regulatory relationship between NKD1 and YWHAE and the mechanism of NKD1 for promoting tumor cell proliferation.@*METHODS@#HCT116 cells transfected with pcDNA3.0-NKD1 plasmid, SW620 cells transfected with NKD1 siRNA, HCT116 cells with stable NKD1 overexpression (HCT116-NKD1 cells), SW620 cells with nkd1knockout (SW620-nkd1-/- cells), and SW620-nkd1-/- cells transfected with pcDNA3.0-YWHAE plasmid were examined for changes in mRNA and protein expression levels of YWHAE using qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NKD1 to the promoter region of YWHAE gene. The regulatory effect of NKD1 on YWHAE gene promoter activity was analyzed by dual-luciferase reporter gene assay, and the interaction between NKD1 and YWHAE was analyzed with immunofluorescence assay. The regulatory effect of NKD1 on glucose uptake was examined in the tumor cells.@*RESULTS@#In HCT116 cells, overexpression of NKD1 significantly enhanced the expression of YWHAE at both the mRNA and protein levels, while NKD1 knockout decreased its expression in SW620 cells (P < 0.001). ChIP assay showed that NKD1 protein was capable of binding to the YWHAE promoter sequence; dual luciferase reporter gene assay showed that NKD1 overexpression (or knockdown) in the colon cancer cells significantly enhanced (or reduced) the transcriptional activity of YWHAE promoter (P < 0.05). Immunofluorescence assay demonstrated the binding of NKD1 and YWHAE proteins in colon cancer cells. NKD1 knockout significantly reduced glucose uptake in colon cancer cells (P < 0.01), while YWHAE overexpression restored the glucose uptake in NKD1-knockout cells (P < 0.05).@*CONCLUSION@#NKD1 protein activates the transcriptional activity of YWHAE gene to promote glucose uptake in colon cancer cells.

Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy / 中华胃肠外科杂志

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

Landmark vessel in membrane anatomy-based colorectal surgery / 中华胃肠外科杂志

The theory of membrane anatomy has been widely used in the field of colorectal surgery. The key point to perform high quality total mesorectal excision (TME) and complete mesocolic excision (CME) is to identify the correct anatomical plane. Intraoperative identification of the various fasciae and fascial spaces is the key to accessing the correct surgical plane and surgical success. The landmark vessels refer to the small vessels that originate from the original peritoneum on the surface of the abdominal viscera during embryonic development and are produced by the fusion of the fascial space. From the point of view of embryonic development, the abdominopelvic fascial structure is a continuous unit, and the landmark vessels on its surface do not change morphologically with the fusion of fasciae and have a specific pattern. Drawing on previous literature and clinical surgical observations, we believe that tiny vessels could be used to identify various fused fasciae and anatomical planes. This is a specific example of membrane anatomical surgery.

Membrane anatomy in right colon cancer: definition and identification of mesocolic completeness / 中华胃肠外科杂志

Complete mesocolic excision (CME) and D3 resection of right colon cancer have been widely implemented, but the definition and identification of the completeness of the mesentery have not been fully agreed, especially the dorsal and medial borders. In this paper, we proposed the dorsal fascia of the colonic mesentery as the dorsal border of the mesocolon and the line connecting the roots of the ileocolic artery and the middle colic artery (ICA-MCA line) as the medial border of the CME by systematically studying the relationship between the mesentery and the mesenteric bed from the theory of membrane anatomy, combined with surgical experience and in-depth review of ontogenetic anatomy. We also proposed the visible "superior mesenteric vein notch" and "middle colic artery triangle" on surgical specimens as identifiers of mesocolic completeness.