Infliximab en enfermedad inflamatoria intestinal. ¿Es necesario premedicar? / Infliximab in inflammatory bowel disease. Is premedication necessary?

Introducción: El uso de infliximab (IFX) en enfermedad inflamatoria intestinal (EII) se ha asociado con un riesgo de 1-6% de reacciones a la infusión. La utilidad de premedicación con corticoides, paracetamol y/o antihistamínicos es controvertido. Objetivo: Evaluar si en pacientes con EII que utilizan IFX hay diferencias en las reacciones secundarias a infusión entre aquellos que utilizan o no premedicación. Métodos: Estudio descriptivo, observacional, retrospectivo en pacientes con EII, que han utilizado IFX entre enero 2009 y julio 2019. Se definieron como reacciones agudas aquellas ocurridas en las primeras 24 hrs.postinfusión y tardías después de ese período, clasificándose en leves, moderadas y severas. Se usó estadística descriptiva y de asociación (χ2; p < 0,05). Resultados: Se incluyeron 1.263 infusiones en un total de 64 pacientes, 52% hombres. Mediana de infusiones por paciente 22 (2-66). El 100% de las infusiones en inducción fueron con premedicación y en mantenimiento el 57%. La premedicación fue realizada con hidrocortisona, clorfenamina y paracetamol. La mayoría de las reacciones fueron agudas, de gravedad leve a moderada y ningún paciente necesitó descontinuar IFX. En mantenimiento hubo 9/718 (1,2%) reacciones a la infusión con premedicación y 4/358 (1,1%) sin ésta, sin diferencias significativas (p = 0,606). En inducción hubo 8/187 (4,3%) reacciones a la infusión, significativamente mayor al compararlas con ambos grupos de mantenimiento. Conclusión: En esta cohorte de pacientes, el no usar premedicación en fase de mantenimiento de IFX no aumentó el número de eventos adversos a este fármaco. Estos resultados sugieren que su indicación no sería necesaria.(AU)

Background: The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. Aim: The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. Methods: A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). Results: Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. Conclusions: In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.(AU)

Resultados quirúrgicos y oncológicos de pacientes operados por cáncer de recto con asistencia robótica / Surgical and oncological results of patients operated for rectal cancer with robotic assistance

Resumen Objetivo: Analizar los resultados quirúrgicos y oncológicos de pacientes con adenocarcinoma de recto (AR) operados con asistencia robótica. Materiales y Método: Cohorte prospectiva entre 2014-2019. Criterios de inclusión: pacientes con AR primario, sometidos a una resección de recto con asistencia robótica con intención curativa. Criterios de exclusión: histología no adenocarcinoma. Evaluación de datos clínico-quirúrgicos. Análisis estadístico descriptivo. Resultados: Se incluyeron 37 pacientes; 20 (54%) fueron hombres y la edad promedio fue 58,7 años. La distancia promedio desde el margen anal al borde distal del tumor fue 6,6 cm (i: 2-12 cm). La quimiorradioterapia (neoadyuvancia) se indicó en 26 pacientes. La cirugía más frecuente fue la resección anterior baja de recto y el tiempo operatorio promedio fue 266 min. Se realizaron dos conversiones a laparotomía. Una o más complicaciones se observaron en 17 (45,9%) pacientes, 9 de ellos fueron Clavien-Dindo III o IV y se reoperaron 5 pacientes (13%). No hubo transfusiones sanguíneas ni mortalidad posoperatoria. La estancia hospitalaria postoperatoria promedio fue 9,6 días (i: 3-34 d). El promedio de linfonodos resecados fue 15 (i 4-45). Los márgenes quirúrgicos fueron negativos en todos los pacientes. Se restituyó el tránsito intestinal en 28/32 (87,5%) pacientes. El promedio de seguimiento fue 21 meses (1-56), la sobrevida global y libre de enfermedad fue 100%. Discusión y Conclusión: La proctectomía con asistencia robótica ha demostrado ser segura en términos de resultados quirúrgicos tempranos y en criterios oncológicos de la pieza operatoria.

Aim: To analyze the surgical and oncological results of patients with rectal adenocarcinoma (RA) operated with robotic assistance. Materials and Method: Prospective cohort study, consecutive sample of patients between 2014-2017. Inclusion criteria: patients with primary RA, undergoing rectal resection, with robotic assistance with curative intention. Exclusion criteria: histology not adenocarcinoma. Evaluation of clinical-surgical data. Descriptive statistical analysis. Results: 37 patients were included; 20 (54%) were men and average age was 58.7 years. The average distance from the anal margin to the distal edge of the tumor was 6.6 cm (2-12 cm). Chemoradiotherapy (neoadyuvant) was indicated in 26 patients. The most frequent surgery was low anterior resection of the rectum and the average operating time was 266 minutes. Two conversions to laparotomy were performed. One or more complications were observed in 17 (45.9%) patients, 9 of them were Clavien-Dindo III or IV, 5 patients (13%) were reoperated. There were no blood transfusions and no postoperative mortality. The average postoperative hospital stay was 9.6 days (3-34). The average of resected lymph nodes was 15. Surgical margins were negative in all patients. Intestinal transit was restored in 28/32 (87.5%) patients. The average follow-up was 21 months (1-56), the overall and disease-free survival was 100%. Discussion and Conclusion: Proctectomy with robotic assistance has proved to be safe in terms of early surgical results and oncologic indicators of the surgical piece.

Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena / Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort

Introducción: El diagnóstico de enfermedad inflamatoria intestinal (EII) se realiza, en un alto porcentaje, durante la edad reproductiva. La EII en remisión es el mejor escenario para planificar el embarazo. Objetivos: Describir las características clínicas del embarazo y del recién nacido, evaluando la actividad de la enfermedad en el momento de la concepción y en la evolución del embarazo en un centro terciario en Chile. Métodos: Estudio observacional, retrospectivo, incluyó a mujeres con EII que habían tenido un parto durante 2017-2020. Los datos demográficos, clínicos y obstétricos se obtuvieron del Registro de EII. Se realizó análisis estadístico descriptivo y de asociación (χ2, p ≤ 0,05). Resultados: Se incluyeron 60 mujeres en el estudio. Al inicio del embarazo, 21 (35%) presentaban actividad inflamatoria y 39 (65%) estaban en remisión. Del grupo con actividad, 16 (66%) permanecieron activas y seis tuvieron un aborto espontáneo. Aquellas en remisión, 26 (69%) permanecieron en esta condición; nueve pacientes (15%) habían suspendido el tratamiento, seis de las cuales presentaron actividad durante el embarazo. El consejo preconcepcional fue realizado en 23/60 pacientes, siendo mayor en el grupo que permaneció en remisión durante el embarazo (65% vs. 35%, p = 0,02). Pacientes con brotes durante el embarazo tuvieron mayor probabilidad de embarazo pretérmino (< 37 semanas) y recién nacido de menor peso comparado con el grupo que permaneció en remisión (89 vs. 74%; p = 0,161) y (2,885 vs. 3,370 g; p = 0,0014), respectivamente. Conclusión: La remisión durante el embarazo presenta los mejores resultados y el consejo preconcepcional permite un mejor control de la EII durante el embarazo.(AU)

Background: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. Aims: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. Methods: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). Results: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). Conclusion: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.(AU)

Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort. / Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena.

BACKGROUND: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. AIMS: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. METHODS: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). RESULTS: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). CONCLUSION: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.

¿Están recibiendo los pacientes con enfermedad inflamatoria intestinal una adecuada inmunización? / Are patients with inflammatory bowel disease receiving adequate immunisation?

Introducción: El tratamiento de la enfermedad inflamatoria intestinal (EII) puede aumentar el riesgo de infección. La inmunización es parte del manejo integral de la atención de estos pacientes. El objetivo de este estudio es describir la prescripción y adherencia a la vacunación en pacientes con EII e identificar los posibles factores asociados a esta. Métodos: Estudio analítico, descriptivo, transversal en pacientes de un Programa de EII de Chile, entre abril y junio de 2019. A los pacientes se les solicitó responder un cuestionario acerca de la adherencia a la vacunación. La información de las vacunas se obtuvo del Registro Nacional de Inmunizaciones. Se realizó análisis estadístico descriptivo y de asociación (χ2; p<0,05). Resultados: Se incluyeron 243 pacientes con EII (148 colitis ulcerosa [CU], 86 enfermedad de Crohn [EC] y 9 EII no clasificable). Solo 6 pacientes (2%) recibieron el esquema de inmunización completo. Las vacunas con los mayores porcentajes fueron contra la influenza (67%), virus hepatitis B (40%), neumocócica 13-valente (34%) y neumocócica 23-polisacárida (16%), siendo las dos primeras más frecuentes en EC vs. CU (p≤0,05). La administración de la vacuna contra la influenza ha aumentado significativamente, alcanzando un 67% el 2019. La encuesta mostró que el 23% no ha sido inmunizado con ninguna vacuna, principalmente por falta de tiempo, falta de prescripción médica y el alto costo económico. Conclusiones: En esta cohorte, aunque las tasas de vacunación son más altas que las reportadas previamente, la adherencia al programa de inmunización debe mejorar, siendo consideradas desde el diagnóstico por el equipo multidisciplinario.(AU)

Introduction: Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunizations in IBD and identify possible associated factors. Methods: A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary center in Chile, between April – June 2019. Patients were asked to answer a vaccine survey and information also was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p<0.05). Results: A total of 243 patients were included (148 ulcerative colitis (UC), 86 Crohn's disease (CD) and 9 non-classifiable IBD). Only six patients (2%) of IBD patients received a complete immunization schedule. The highest vaccine rates were against influenza (67%), hepatitis B virus (40%), 13-valent pneumococcal (34%) and 23-polysaccharide pneumococcal (16%). The influenza vaccine rate has significantly increased, reaching 67% in 2019. The survey showed that 23% of patients have not been immunized with any vaccine, mainly due to lack of time, lack of medical prescription and high cost. Conclusions: In this cohort, although vaccination rates are higher than previously reported, adherence to IBD immunization program would be improved, being considered since diagnosis by the multidisciplinary team.(AU)

Infliximab in inflammatory bowel disease. Is premedication necessary? / Infliximab en enfermedad inflamatoria intestinal. ¿Es necesario premedicar?

BACKGROUND: The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. AIM: The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. METHODS: A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). RESULTS: Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. CONCLUSIONS: In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.

Are patients with inflammatory bowel disease receiving adequate immunisation? / ¿Están recibiendo los pacientes con enfermedad inflamatoria intestinal una adecuada inmunización?

INTRODUCTION: Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunizations in IBD and identify possible associated factors. METHODS: A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary center in Chile, between April - June 2019. Patients were asked to answer a vaccine survey and information also was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p<0.05). RESULTS: A total of 243 patients were included (148 ulcerative colitis (UC), 86 Crohn's disease (CD) and 9 non-classifiable IBD). Only six patients (2%) of IBD patients received a complete immunization schedule. The highest vaccine rates were against influenza (67%), hepatitis B virus (40%), 13-valent pneumococcal (34%) and 23-polysaccharide pneumococcal (16%). The influenza vaccine rate has significantly increased, reaching 67% in 2019. The survey showed that 23% of patients have not been immunized with any vaccine, mainly due to lack of time, lack of medical prescription and high cost. CONCLUSIONS: In this cohort, although vaccination rates are higher than previously reported, adherence to IBD immunization program would be improved, being considered since diagnosis by the multidisciplinary team.

Characterization of Chilean patients with sporadic colorectal cancer according to the three main carcinogenic pathways: Microsatellite instability, CpG island methylator phenotype and Chromosomal instability.

Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher's exact and/or chi-square test. Survival curves were estimated with Kaplan-Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.

Spectrum and Frequency of Tumors, Cancer Risk and Survival in Chilean Families with Lynch Syndrome: Experience of the Implementation of a Registry.

Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p < 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.

The Role of an Inflammatory Bowel Disease Nurse in the Follow-Up of Patients From a Latin American Inflammatory Bowel Disease Program.

Inflammatory bowel disease requires long-term treatment to maintain disease control. Favorable follow-up of patients indicates attention from a multidisciplinary team, in which the nurse's responsibilities have great importance. The aim of this observational, descriptive study was to describe the role of an inflammatory bowel disease nurse in the management of patients in a tertiary center in Chile, including all patients in follow-up between January 2016 and April 2017. Inflammatory bowel disease nurse contacts were recorded and classified. Demographic data, clinical variables, and patient satisfaction were also analyzed. A total of 597 patients (51%) were in follow-up over the 16-month period; 63% had ulcerative colitis, with a median age of 35 years. The inflammatory bowel disease nurse performed 760 contacts in 253 patients (42% of the follow-up patients). The most frequent nurse interventions were reinforcement of medical indications (42%), assessment of laboratory results (17%), and disease follow-up (12%); 49% related to education. Nurse interventions were focused in more severely ill patients; flares during the follow-up, biological therapy, immunomodulators, and steroids were all statistically significant. Of a sample of 107 patients surveyed, 96% perceived the inflammatory bowel disease program as excellent/good. The inflammatory bowel disease nurse plays an important role in the follow-up and management, specifically in education, of more severely ill patients.

Colorectal cancer risk factors in asymptomatic Chilean population: a survey of international collaboration between Japan and Chile.

In Chile, the mortality from colorectal cancer has been on the rise. A national screening program based on a fecal immunochemical test was started in 2012 as an international collaboration with Japan. This case-control study was designed to identify the risk factors for colorectal cancer, with a goal of increasing the participation rate for colorectal cancer screening. In accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, we conducted a case-control study from 2012 to 2017; 23 845 asymptomatic participants were enrolled in the study. Participants who were fecal immunochemical test-positive or had a family history of colorectal cancer underwent a colonoscopy. We analyzed the odds ratio of the risk factors for colorectal cancer, including sex, age, family history, BMI, hypertension, diabetes, regular use of nonsteroidal anti-inflammatory drugs, alcohol consumption, smoking, physical activity, and daily intake of certain food items. For the screening program, 202 cases of colorectal cancer were detected, and 195 of them were evaluated pathologically after resection. Of these, 173 cases (88.7%) had colorectal cancer stage 0/1, 151 (77.4%) of which were treated with endoscopic resection. In the multivariate analysis, male sex, family history of colorectal cancer, and low intake of cereals or fibers were closely related to a high colorectal cancer incidence. Moreover, participants in their 60s and 70s had a higher incidence of colorectal cancer than those in their 50s. These results suggest that intensive screening of the high-risk population can help in improving the detection of colorectal cancer, whereas higher consumption of cereals or fibers can be effective in preventing its onset.

Corrigendum: Interleukin 33/ST2 Axis Components Are Associated to Desmoplasia, a Metastasis-Related Factor in Colorectal Cancer.

[This corrects the article DOI: 10.3389/fimmu.2019.01394.].

Interleukin 33/ST2 Axis Components Are Associated to Desmoplasia, a Metastasis-Related Factor in Colorectal Cancer.

In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) are the most abundant component from the tumor microenvironment (TM). CAFs facilitate tumor progression by inducing angiogenesis, immune suppression and invasion, thus altering the organization/composition of the extracellular matrix (i.e., desmoplasia) and/or activating epithelial-mesenchymal transition (EMT). Soluble factors from the TM can also contribute to cell invasion through secretion of cytokines and recently, IL-33/ST2 pathway has gained huge interest as a protumor alarmin, promoting progression to metastasis by inducing changes in TM. Hence, we analyzed IL-33 and ST2 content in tumor and healthy tissue lysates and plasma from CRC patients. Tissue localization and distribution of these molecules was evaluated by immunohistochemistry (using localization reference markers α-smooth muscle actin or α-SMA and E-cadherin), and clinical/histopathological information was obtained from CRC patients. In vitro experiments were conducted in primary cultures of CAFs and normal fibroblasts (NFs) isolated from tumor and healthy tissue taken from CRC patients. Additionally, migration and proliferation analysis were performed in HT29 and HCT116 cell lines. It was found that IL-33 content increases in left-sided CRC patients with lymphatic metastasis, with localization in tumor epithelia associated with abundant desmoplasia. Although ST2 content showed similarities between tumor and healthy tissue, a decreased immunoreactivity was observed in left-sided tumor stroma, associated to metastasis related factors (advanced stages, abundant desmoplasia, and presence of tumor budding). A principal component analysis (including stromal and epithelial IL-33/ST2 and α-SMA immunoreactivity with extent of desmoplasia) allowed us to distinguish clusters of low, intermediate and abundant desmoplasia, with potential to develop a diagnostic signature with benefits for further therapeutic targets. IL-33 transcript levels from CAFs directly correlated with CRC cell line migration induced by CAFs conditioned media, with rhIL-33 inducing a mesenchymal phenotype in HT29 cells. These results indicate a role of IL-33/ST2 in tumor microenvironment, specifically in the interaction between CAFs and epithelial tumor cells, thus contributing to invasion and metastasis in left-sided CRC, most likely by activating desmoplasia.

Resultados a largo plazo de pacientes con adenocarcinoma de recto inferior tratados con resección anterior ultrabaja interesfintérica / Long-term results of patients with adenocarcinoma of the lower rectum treated with anterior intersphinteric ultra-low-resection

INTRODUCCIÓN: La resección anterior ultrabaja interesfintérica (RAUBIE), permite preservar la función esfinteriana en pacientes seleccionados con cáncer de recto (CR). No obstante, puede producir alteraciones en la función evacuatoria y esfinteriana. OBJETIVO: Analizar los resultados oncológicos y funcionales luego de una RAUBIE. MATERIAL Y MÉTODO: Estudio observacional, analítico, transversal, durante el período 2007 a 2016. Criterios de inclusión: Pacientes sometidos a RAUBIE por CR con intención curativa. Todos los pacientes tuvieron un seguimiento el año 2017. Para la evaluación funcional se usó la escala de Jorge-Wexner, LARS y Kirwan. Análisis estadístico: Estadística descriptiva y método de Kaplan-Meier. RESULTADOS: De 21 pacientes; catorce (67%) fueron varones, edad promedio: 59 años. Ubicación tumoral: 4 cm (2-6 cm) del margen anal. Dieciocho (85,7%) pacientes recibieron neoadyuvancia. Todos los márgenes quirúrgicos distales y radiales fueron negativos. Un paciente (4,8%) tuvo metástasis a distancia y no hubo recurrencia locorregional. Con una mediana de seguimiento de 76,3 (9,8-126,8) meses, la sobrevida global y libre de enfermedad a 5 años fue de: 100% y 95% (IC: 90,1-99,9%), respectivamente. Con una mediana de seguimiento de 90 meses (21,7-124,2); se realizó la evaluación funcional a 15/21 pacientes. El puntaje de Jorge-Wexner tuvo una mediana de 13 (4-17) puntos, la escala de LARS de 34 puntos y en la escala de Kirwan, cuatro pacientes (26,7%) mostraron una buena función (Kirwan I-II). CONCLUSIÓN: Si bien los resultados oncológicos de los pacientes sometidos a una RAUBIE son satisfactorios, se debería tomar en cuenta los resultados funcionales al momento de proponer esta alternativa quirúrgica.

INTRODUCTION: Intersphinteric resection (ISR) allows preserve sphincter function in selected patients with rectal cancer (RC). Notwithstanding, it can produce alterations in defecation. AIM: To analyze the oncological and functional results after an ISR. MATERIAL AND METHOD: Observational, analytical, cross-sectional study, in the period 2007-2016. Inclusion criteria: Patients submitted to ISR by RC with curative intention. All the patients had a follow-up in 2017. Analysis of functional evaluation were performed by Jorge-Wexner, LARS and Kirwan scale. Statistical analysis: Descriptive statistics and Kaplan-Meier method. RESULTS: Of 21 patients; Fourteen (67%) were male, average age: 59 years. Tumor location: 4 cm (2-6 cm) from anal verge. Eighteen (85.7%) patients received neoadjuvant therapy. All distal and radial margins were negative. One patient (4.8%) had distant metastases and there was no locoregional recurrence. With a median follow-up of 76.3 (9.8-126.8) months, the 5-year global and disease-free survival was: 100% and 95% (CI: 90.1-99.9%), respectively. With a median follow-up of 90 months (21.7-124.2); Functional evaluation was performed on 15/21 patients. The Jorge-Wexner score had a median of 13 (4-17) points, the LARS scale of 34 points and in Kirwan scale, four patients (26.7%) showed good function (Kirwan I-II). CONCLUSION: The oncological results of patients undergoing ISR are satisfactory, however, functional results should be taken into account when proposing this surgical procedure.

[Environmental risk factors in the development and evolution of inflammatory bowel disease]. / Factores ambientales en el desarrollo y evolución de la enfermedad inflamatoria intestinal.

Environmental factors may influence the development of Inflammatory Bowel Disease and modify its natural history. The objective of this review is to evaluate current evidence about environmental factors associated with the disease. A better knowledge about the pathogenesis of the disease can lead to better treatment strategies and suggestions to prevent the disease.

Factores ambientales en el desarrollo y evolución de la enfermedad inflamatoria intestinal / Environmental risk factors in the development and evolution of inflammatory bowel disease

Environmental factors may influence the development of Inflammatory Bowel Disease and modify its natural history. The objective of this review is to evaluate current evidence about environmental factors associated with the disease. A better knowledge about the pathogenesis of the disease can lead to better treatment strategies and suggestions to prevent the disease.

Histopathologic study from a colorectal cancer screening in Chile: results from the first 2 years of an international collaboration between Chile and Japan.

A national colorectal cancer (CRC) screening program began in Chile in 2012, which is an international collaboration between Japan and Chile and is based on a standardized protocol supported by Tokyo Medical and Dental University. We describe the results from the first 2 years of screening at one public hospital in Punta Arenas, Chile. Of 4124 asymptomatic individuals aged between 50 and 75 years, 485 participants with immunological fecal occult blood test values of at least 100 ng/ml and/or those with family histories of CRC underwent colonoscopies. Lesions were found in 291 participants, and 642 histologic samples were obtained. Chilean pathologists made the initial histologic diagnoses, and a Japanese pathologist reviewed the histologic slides and analyzed the results. Of the 291 participants with lesions, 60 (20.6%) were diagnosed with adenocarcinomas, of which 50 (83.3%) were early-phase adenocarcinomas (pTis or pT1), and 163 (56.0%) were diagnosed with conventional adenomas, of which 96 (58.9%) were high-risk adenomas. The cancer prevalence within the screened population was 1.5% (60 of 4124). The colonoscopy cancer detection rate was 12.4% (60 of 485). Notably, we detected one flat-depressed (0-IIc) lesion that measured 5 mm and had invaded the submucosa. The findings from this screening program are the first to show the histopathologic distributions of consecutive lesions and the high incidence of CRC in Chile. The high detection rates for high-risk adenomas and cancer support the feasibility of early CRC screening and its potential to reduce the mortality associated with CRC.

The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer.

A complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma chemokine levels involved in macrophage recruitment with tumor-associated macrophage profile markers and clinicopathological features such as tumor-node-metastases stage, desmoplasia, tumor necrosis factor-α, and vascular endothelial growth factor plasma content. Plasma and tumor/healthy mucosa were obtained from Chilean patients undergoing colon cancer surgery. Chemokines were evaluated from tissue lysates (CCL2, CCL3, CCL4, CCL5, and CX3CL1) by Luminex. Statistical analysis was performed using Wilcoxon match-paired test ( p < 0.05). Macrophage markers (CD68, CD163, and iNOS) were evaluated by immunohistochemistry samples derived from colorectal cancer patients. Correlation analysis between chemokines and macrophage markers and clinicopathological features were performed using Spearman's test. Plasmatic levels of chemokines and inflammatory mediators' vascular endothelial growth factor and tumor necrosis factor-α were evaluated by Luminex. Tumor levels of CCL2 (mean ± standard deviation = 530.1 ± 613.9 pg/mg), CCL3 (102.7 ± 106.0 pg/mg), and CCL4 (64.98 ± 48.09 pg/mg) were higher than those found in healthy tissue (182.1 ± 116.5, 26.79 ± 22.40, and 27.06 ± 23.69 pg/mg, respectively p < 0.05). The tumor characterization allowed us to identify a positive correlation between CCL4 and the pro-tumor macrophages marker CD163 ( p = 0.0443), and a negative correlation of iNOS with desmoplastic reaction ( p = 0.0467). Moreover, we identified that tumors with immature desmoplasia have a higher CD163 density compared to those with a mature/intermediated stromal tissue ( p = 0.0288). Plasmatic CCL4 has shown a positive correlation with inflammatory mediators (tumor necrosis factor-α and vascular endothelial growth factor) that have previously been associated with poor prognosis in patients. In conclusion High expression of CCL4 in colon cancer could induce the infiltration of tumor-associated macrophages and specifically a pro-tumor macrophage profile (CD163+ cells). Moreover, plasmatic chemokines could be considered inflammatory mediators associated to CRC progression as well as tumor necrosis factor-α and vascular endothelial growth factor. These data reinforce the idea of chemokines as potential therapeutic targets or biomarker in CRC.