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.

SELF-CONFIDENCE ON ACQUIRED SURGICAL SKILLS TO DEAL WITH SEVERE TRAUMA PATIENTS IN RECENTLY GRADUATED SURGEONS.

BACKGROUND: Level of competence by procedure. Trauma is one of the leading causes of death in the world and proper surgical care is critical to impact mortality. In Chile, trauma associated death ranks first as mortality cause in population between 20 and 59 years old. Appropriate surgical skills are required to deal with these complex patients. Self-confidence to practice trauma procedures after the General Surgery Residency have not been reported in our country. AIM: Describe the level of self-confidence to deal with trauma procedures of surgeons who recently graduated from a General Surgery Residency. METHOD: Descriptive cross-sectional study. We designed and applied a survey in 2015, 2016 and 2017 to recently graduated surgeons, to inquire about self-confidence of surgical skills to deal with trauma scenarios. Eighteen trauma surgery procedures (including cervical, thoracic, abdominal and vascular procedures) were evaluated using a 5-grade Likert scale. The number of procedures performed during the residency was also queried. RESULTS: Eighty-eight recently graduated surgeons from 11 different training programs in Chile were included. The report of competencies was high in procedures such as intestinal injuries, were 98% felt competent or very competent in their repair. On the other hand, in complex traumas such as major vessel injury, up to 76% reported not being competent. Self-confidence on procedures was directly associated with the number of procedures performed during residency. CONCLUSIONS: Recently graduated surgeons from General Surgery Programs report high levels of confidence to deal with low and intermediate complexity traumas, but a lower level of confidence to treat high complexity cases.

Computed tomography-measured body composition parameters do not influence survival in non-metastatic colorectal cancer.

BACKGROUND: There is an increasing interest in studying the impact of altered body composition parameters and colorectal cancer (CRC) treatment outcomes. The aim of this study is to explore the impact of computed tomography (CT)-measured visceral obesity, sarcopenia and myosteatosis on survival of non-metastatic CRC. METHODS: Consecutive patients with stage I-III CRC who underwent curative-intent treatment between January 2010 and December 2015 were included. By measuring the visceral fat area, and the skeletal muscle index and radiodensity in the pre-operative staging CT, patients were classified as visceral obese, sarcopenic or myosteatotic. The associations between CT-based body composition parameters and survival were assessed using log-rank tests and a Cox regression analysis. RESULTS: Of 359 patients, 263 (73.3%) were visceral obese, 85 (23.7%) sarcopenic and 80 (22.3%) myosteatotic. Overall (OS), cancer-specific (CSS) and disease-free survivals (DFS) at 5 years were 78.8%, 84.7% and 75%, respectively. Myosteatosis and the combination of myosteatosis and visceral obesity were associated with a reduced DFS (hazard ratio 1.67; 95% confidence interval 1.06-2.61 and hazard ratio 1.85; 95% confidence interval 1.15-2.96, respectively). However, after performing a multivariate analysis including other relevant clinicopathological factors, none of the body composition parameters were associated with any long-term outcome measures, even after stratifying by cancer stage. CONCLUSIONS: CT-measured body composition parameters do not independently influence survival in non-metastatic CRC. There is a need for larger cohort studies with standardized patient selection and methodology to confirm these findings.

Implementation of intracorporeal anastomosis in laparoscopic right colectomy is safe and associated with a shorter hospital stay.

Reconstruction after laparoscopic right colectomy (LRC) can be achieved by performing an intracorporeal (IA) or an extracorporeal anastomosis (EA). This study aims to assess the safety of implementing IA in LRC, and to compare its perioperative outcomes with EA during an institution's learning curve. Patients undergoing elective LRC with IA or EA in a teaching university hospital between January 2015 and December 2018 were included. Demographic, clinical, perioperative and histopathological data were collated and outcomes investigated. One hundred and twenty-two patients were included; forty-three (35.2%) had an IA. The main indication for surgery was cancer in both groups (83.7% for IA and 79.8% for EA; p = 0.50). Operative time was longer for IA (180 [150-205] versus 150 [120-180] minutes; p < 0.001). A Pfannenstiel incision was used as extraction site in 97.7% of patients receiving an IA; while a midline incision was used in 97.5% of patients having an EA (p < 0.001). Hospital stay was significantly shorter for IA (3 [3, 4] versus 4 [3-6] days; p = 0.003). There were no differences in postoperative complications rates between groups. There was a 4.7% and 3.8% anastomotic leak rate in the IA and EA group, respectively (p = 1). Re-intervention and readmission rates were similar between groups, and there was no mortality during the study period. The implementation of IA in LRC is safe. Despite longer operative times, IA is associated with a shorter hospital stay when compared to EA in the setting of an institution's learning curve.

Self-confidence on acquired surgical skills to deal with severe trauma patients in recently graduated surgeons / Autoconfiança nas habilidades cirúrgicas adquiridas para lidar com pacientes com trauma grave em cirurgiões recém-formados

ABSTRACT Background: Trauma is one of the leading causes of death in the world and proper surgical care is critical to impact mortality. In Chile, trauma associated death ranks first as mortality cause in population between 20 and 59 years old. Appropriate surgical skills are required to deal with these complex patients. Self-confidence to practice trauma procedures after the General Surgery Residency have not been reported in our country. Aim: Describe the level of self-confidence to deal with trauma procedures of surgeons who recently graduated from a General Surgery Residency. Method: Descriptive cross-sectional study. We designed and applied a survey in 2015, 2016 and 2017 to recently graduated surgeons, to inquire about self-confidence of surgical skills to deal with trauma scenarios. Eighteen trauma surgery procedures (including cervical, thoracic, abdominal and vascular procedures) were evaluated using a 5-grade Likert scale. The number of procedures performed during the residency was also queried. Results: Eighty-eight recently graduated surgeons from 11 different training programs in Chile were included. The report of competencies was high in procedures such as intestinal injuries, were 98% felt competent or very competent in their repair. On the other hand, in complex traumas such as major vessel injury, up to 76% reported not being competent. Self-confidence on procedures was directly associated with the number of procedures performed during residency. Conclusions: Recently graduated surgeons from General Surgery Programs report high levels of confidence to deal with low and intermediate complexity traumas, but a lower level of confidence to treat high complexity cases.

RESUMO Racional: Trauma é uma das principais causas de morte no mundo e cuidados cirúrgicos adequados são críticos para determinar a mortalidade. No Chile, morte associada a trauma é a primeira causa de mortalidade na população entre 20 e 59 anos. Para lidar com esses pacientes complexos, são necessárias habilidades cirúrgicas precisas para esses procedimentos. Autoconfiança de cirurgiões recentemente graduados na Residência em Cirurgia Geral para práticas de procedimentos de trauma no nosso país não tem sido reportada. Objetivo: Descrever nível de autoconfiança para lidar com procedimentos de trauma em cirurgiões recentemente graduados na residência de cirurgia geral. Método: Estudo transversal. Foi desenhada e aplicada uma enquete em 2015, 2016 e 2017 a cirurgiões recentemente graduados para pesquisar sobre autoconfiança e habilidades cirúrgicas para lidar com cenários de trauma. Foram avaliados 18 procedimentos cirúrgicos de trauma (incluindo procedimentos cervicais, torácicos, abdominais e vasculares) usando a 5-grade Likert Scale. O número total de procedimentos feitos durante a residência foi avaliado. Resultados: Foram incluídos 88 cirurgiões recentemente graduados. O nível de competência foi reportado como alto em procedimentos como trauma intestinal, onde 98% sentiu-se competente ou muito competente em sua reparação. Por outro lado, em traumas complexos como dano vascular maior, até 76% reportaram não se sentirem competentes. A autoconfiança nos procedimentos esteve diretamente associada com o número de procedimentos realizados. Conclusões: Cirurgiões recentemente graduados na residência de cirurgia geral reportam níveis altos de confiança para lidar com traumas de complexidade baixa e média, mas um nível menor de confiança para tratar casos de complexidade alta.

fMLP-Induced IL-8 Release Is Dependent on NADPH Oxidase in Human Neutrophils.

N-Formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) induce similar intracellular signalling profiles; but only fMLP induces interleukin-8 (IL-8) release and nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity in neutrophils. Because the role of ROS on IL-8 release in neutrophils is until now controversial, we assessed if NADPH oxidase is involved in the IL-8 secretions and PI3K/Akt, MAPK, and NF-κB pathways activity induced by fMLP. Neutrophils were obtained from healthy volunteers. IL-8 was measured by ELISA, IL-8 mRNA by qPCR, and ROS production by luminol-amplified chemiluminescence, reduction of ferricytochrome c, and FACS. Intracellular pH changes were detected by spectrofluorescence. ERK1/2, p38 MAPK, and Akt phosphorylation were analysed by immunoblotting and NF-κB was analysed by immunocytochemistry. Hydroxy-3-methoxyaceto-phenone (HMAP), diphenyleneiodonium (DPI), and siRNA Nox2 reduced the ROS and IL-8 release in neutrophils treated with fMLP. HMAP, DPI, and amiloride (a Na(+)/H(+) exchanger inhibitor) inhibited the Akt phosphorylation and did not affect the p38 MAPK and ERK1/2 activity. DPI and HMAP reduced NF-κB translocation induced by fMLP. We showed that IL-8 release induced by fMLP is dependent on NADPH oxidase, and ROS could play a redundant role in cell signalling, ultimately activating the PI3K/Akt and NF-κB pathways in neutrophils.