Background: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP (Rev Med Chile 2017; 145: 419-430)

Introduction: Colorectal cancer (CRC) represents a major health problem worldwide, ranking third among the most frequent cancers and fourth in cancer mortality. In Chile CRC is the third leading cause of cancer death. CRC is a heterogeneous disease, and three carcinogenic pathways have been described to determine the molecular profile: The microsatellite instability (MSI), chromosomal instability (CIN) and methylator phenotype (CIMP). Several studies have tried to propose CRC molecular subgroups based on the 3ways described above since CIN, MSI and CIMP are not mutually exclusive and overlapping of the 3 ways is still unclear. The most recent subtyping of CRC was in 2015, where four molecular subtypes consensus (CMS 1 to 4) were established according to clinicopathological features, molecular pathways involved and mutational status of KRAS, BRAF and PI3KCA genes in order to encourage clinical translation. 21% of tumors failed to be categorized into these subtypes. This classification allows us to understand and determine the clinical, pathological and biological characteristics of CCR to provide customized therapies to patients. Aim: To describe the molecular profile of carcinogenic pathways CIN, MSI CIMP in Chilean patients with sporadic CRC. Material and Methods: Prospective analytical study of 56 patients operated between 2010-2016 at Clinica Las Condes, without neo-adjuvant treatment. DNA was extracted from normal and tumor tissue of each patient and using PCR amplification of several markers CIN, MSI and CIMP were defined. By combining the 3 variables analyzed, tumors were classified in Group-A (MSI-high), Group-B (MSI-low / CIMP-high / CIN-high), Group-C (MSI-low / CIMP-high / CIN-low), Group-D (MSI-low / CIMP-low / CIN-high) and Group-E (MSI- neg / CIMP-neg / CIN-neg). Results: In this study, tumors in Group-A (17%) are located on the right side in patients older than 60 years and early stages. Tumors Group-B / C (18,9%) occur in patients older than 60 years and BMI>25 kg / m2, with wall invasion pT3-T4 and late stages. Tumors of Group-D / E (54,7%) are the most frequent, located on the left side, without vascular invasion and moderately differentiated. Conclusions: This study allowed to classify Chilean patients in 3 subgroups considering the 3 main routes described for carcinogenesis development: CIN, MSI and CIMP, which are consistent with the percentages described by the global consortium. Studies that analyze MSI and CIMP or MSI and CIN have consistently shown that patients with MSI-high tumors have a better prognosis (in our case 17%). Despite therapeutic advances based on this molecular characterization, both the heterogeneity of tumors and the different combinations of pathways involved have shown that the response to therapy varies depending on the individual profile of each patient, therefore in clinical practice it would be important to establish that profile for each of them. Fondecyt 1140012 Citation Format: Ana Maria Wielandt, Cynthia Villarroel, Claudia Hurtado, Daniela Simian, Diego Zamorano, Maripaz Martinez, Magdalena Castro, Maria Teresa Vial, Udo Kronberg, Francisco Lopez-Kostner. Determination of the molecular profile of Chilean patients with sporadic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3943. doi:10.1158/1538-7445.AM2017-3943

Anastomotic leakage (AL) is a major cause of morbidity and mortality after colorectal surgery, but the mechanism behind this complication is still not fully understood. Despite the advances in surgical techniques and perioperative care, the complication rates have remained steady. Recently, it has been suggested that colon microbiota may be involved in the development of complications after colorectal surgery. The aim of this study was to evaluate the association of gut microbiota in the development of colorectal AL and their possible virulence strategies to better understand the phenomenon. Using 16S rRNA sequencing of samples collected on the day of surgery and the sixth day following surgery, we analyzed the changes in tissue-associated microbiota at anastomotic sites created in a model of rats with ischemic colon resection. We discovered a trend for lower microbial diversity in the AL group compared to non-leak anastomosis (NLA). There were no differences in relative abundance in the different types of microbial respiration between these groups and the high abundance of the facultative anaerobic Gemella palaticanis is a marker species that stands out as a distinctive feature.

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