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.

Calidad del sueño en pacientes con enfermedad inflamatoria intestinal / Sleep quality in inflammatory bowel disease patients

Although inflammatory bowel disease (IBD) etiology is still unknown, genetic, environmental and immunological factors are implicated. Studies have considered quality of sleep as a risk factor in IBD course. Objective: To determine sleep quality in IBD patients, irritable bowel syndrome (IBS) patients and healthy controls (HC). Methods: Cross sectional study assessing sleep quality in adult patients with IBD, IBS and HC. All patients answered a validated Spanish version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire in order to evaluate sleep quality. A PSQI global score > 5 is indicative of poor sleep quality. Demographic and clinical variables were assessed. Results: The study included 276 patients, 111 with IBD, 85 with IBS and 80 HC. A PSQI score > 5 was observed in 67 percent of IBD and IBS patients and 55 percent of HC. IBD and IBS patients exhibited poorer sleep quality than HC, although results did not reach statistical significance (p = 0.069 and p = 0.076, respectively). In IBD patients, an association between disease activity and sleep quality was observed (p = 0.025). However, when analyzing separately patients with ulcerative colitis (UC) and Crohn ́s Disease (CD), only in UC patients sleep quality was related with disease activity. The use of sleep medications was significantly higher in IBD and IBS patients compared with healthy controls (p = 0.021 and p = 0.009, respectively). Conclusion: Sleep disturbances are frequent in IBD, IBS patients and even healthy controls. Additionally, IBD patients with active disease, particularly those with UC, exhibit worse sleep quality.

Aunque la etiología de la enfermedad inflamatoria intestinal (EII) es aún desconocida, factores genéticos, ambientales e inmunológicos estarían implicados. Estudios han considerado la calidad del sueño como un factor de riesgo en la evolución de la EII. Objetivo: Determinar la calidad del sueño en pacientes con enfermedad inflamatoria intestinal (EII), síndrome intestino irritable (SII) y controles sanos (CS). Métodos:Estudio transversal en pacientes adultos con EII, SII y CS. Se evaluó la calidad del sueño mediante el Índice de Calidad del Sueño de Pittsburgh (ICSP), siendo una puntuación global > 5 indicativa de mala calidad del sueño. Variables demográficas y clínicas fueron evaluadas. Resultados:Se incluyeron 276 pacientes, 111 con EII, 85 SII y 80 CS. ICSP > 5 fue observado en 67 por ciento de los pacientes con EII y SII, y 55 por ciento de los CS. Los pacientes con EII y SII mostraron una peor calidad del sueño comparado con CS sin alcanzar significancia estadística (p: 0,069 y p: 0,076, respectivamente). En los pacientes con EII, se observó una asociación entre actividad de la enfermedad y calidad del sueño (p: 0,025). Sin embargo, al analizar por diagnóstico específico, sólo pacientes con colitis ulcerosa (CU) presentaron esta asociación. El uso de medicamentos para dormir fue significativamente mayor en los pacientes con EII y SII comparado con CS (p: 0,021 y p: 0,009, respectivamente). Conclusión:Los trastornos del sueño son frecuentes en pacientes con EII, SII e incluso CS. Pacientes con EII activa, en particular aquellos con CU, presentaron una peor calidad del sueño.