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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Cirugia is the property of Sociedad de Cirujanos de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: In Chile, a national colorectal cancer (CRC) screening program using immunochemical fecal occult blood tests and colonoscopy was started in 2012 as an international collaboration between Chile and Japan. In the present study, we quantified exosomes in the peripheral blood and evaluated the implication of the results for CRC screening. Methods: A total of 25 peripheral plasma samples from the participants of CRC screening in Punta Arenas, Chile, were analyzed for exosomes. Results: Plasma exosomes were obtained from 5 participants with adenocarcinoma (4 pTis and 1 pT1), 8 with high-grade adenoma, 4 with low-grade adenoma, 4 with hyperplastic polyps, and 4 with normal findings. Participants with adenocarcinoma had significantly higher amounts of plasma exosomes (2.1–3.2 fold) than participants with normal findings, hyperplastic polyps, or low-grade adenoma (p = 0.016, p = 0.0034, and p = 0.0042 respectively; Tukey's multiple comparisons test). The size of the representative lesion, the number of lesions, and the sum of those 2 factors in each participant correlated significantly with the exosome amounts (r = 0.56, r = 0.58, and r = 0.72, respectively; p < 0.01; Spearman's correlation coefficient test). Conclusions: This pilot study demonstrated that quantification of plasma exosomes is a potential alternative screening method for detecting individuals with a high risk of colorectal malignancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the correlation between clinical, fecal, endoscopic and histological activity in patients with ulcerative colitis (UC). METHODS: A correlational cross-sectional analysis was performed in patients with UC who underwent colonoscopy between February and December 2016. Clinical, endoscopic, fecal and histological activities were determined using the partial Mayo subscore, Mayo endoscopic subscore and modified Mayo endoscopic subscore, fecal calprotectin and Geboes score and the presence of basal plasmacytosis, respectively. Scores were analyzed using Spearman's rank correlation test. To determine the association between scores and some clinical variables and active UC, univariate and multivariate logistic regressions were used. RESULTS: Altogether 105 procedures (93 patients) were included. In 64.8% of the procedures, the mucosa was inflamed; however, 14.7% did not show histological inflammation. Endoscopic remission was observed in the other 35.2% of procedures; however, in biopsies 21.6% exhibited histological inflammation. Mayo endoscopic subscore and modified Mayo endoscopic score were well correlated but were only moderately correlated with clinical and histological scores. Furthermore, there was a moderate correlation between Mayo endoscopic score and Geboes score. Conversely, histological scores were poorly correlated with partial Mayo score. In multivariate analysis, Geboes score and basal plasmacytosis were predictive of active disease (OR 3.505, 95% CI 1.544-7.959 and OR 3.240, 95% CI 1.123-9.349, respectively), whereas biological therapy was found to be protective against UC (OR 0.021, 95% CI 0.000-0.641). CONCLUSION: Clinical, endoscopic and histological activities were moderately correlated, while Geboes score and basal plasmacytosis were predictive of endoscopically active UC. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a multistep process affecting several signaling pathways including EGFR (epidermal growth factor receptor), a therapeutic target for metastatic disease. Our aim was to characterize the mutational and expression profiles of the EGFR pathway in colorectal tumors and to integrate these results according to five previously defined groups. We screened seven genes for mutations (KRAS-BRAF-PIK3CA-PIK3R1-AKT1-MAP2K1-PTEN) and six proteins (EGFR-p110α-p85α-PTEN-phosphoAKT-phosphoMEK1) by immunohistochemistry, PTEN deletion, and MSI. At least one mutated gene was observed in 68% of tumors (KRAS 45%, PIK3CA 21%, BRAF 14%, and PTEN 7%). PTEN deletion was observed in 10.7% of tumors and 19.6% were MSI-High. In all, 54% of tumors showed a high EGFR expression, 48% p110α, 4.4% phosphoAKT, and 22% phosphoMEK1; and 43% showed low PTEN expression and 22% p85α. In total, five groups of tumors were defined based on MSI, BRAF, and KRAS mutations. Three groups gather mainly early-stage tumors, whereas a fourth group is mostly conformed by advanced tumors. We described here that 71.4% of tumors from one group have a mutated PI3K/PTEN pathway, in comparison to other groups having 32%, 27%, and 25%. In addition, the five groups are differentiated by molecular features such as EGFR, p85α, p110α, and PTEN, showing variable expression among tumor groups. In conclusion, alterations on the EGFR pathway were found in a high percentage of colorectal cancer patients. Using the integration of diverse molecular markers, we ratified previous classification in an ethnic group having relevant genetic differences and living in a different environmental background, adding complementary molecular targets related to therapy. [ABSTRACT FROM AUTHOR]

Aims and objectives To assess disease-related knowledge among patients with inflammatory bowel disease and to identify the factors that are possibly associated with the knowledge level. Background Disease-related knowledge can positively influence the acceptance of the disease, increase treatment compliance and improve the quality of life in patients with inflammatory bowel disease. Design An observational, cross-sectional study was conducted and prospectively included patients from the inflammatory bowel disease programme between October 2014-July 2015. Methods A Spanish-translated version of the 24-item Crohn's and Colitis Knowledge score was used to assess disease-related knowledge. Patients also completed a demographic and clinical questionnaire. Results A total of 203 patients were included, 62% were female, and 66% were diagnosed with ulcerative colitis; the median age was 34 years (range 18-79), and the median disease duration was four years. The median disease-related knowledge score was 9 (range 1-20). Only 29% of the patients answered more than 50% of the questions correctly. Lower disease-related knowledge was observed in questions related to pregnancy/fertility and surgery/complications. Patients older than 50 years, with ulcerative colitis, with disease durations less than five years and patients without histories of surgery exhibited lower disease-related knowledge. There was no association between the knowledge scores and the educational levels. Conclusions The patients who attended our inflammatory bowel disease programme exhibited poor disease-related knowledge that was similar to the knowledge levels that have been observed in developed countries. It is necessary to assess patient knowledge to develop educational strategies and evaluate the influences of these strategies on patient compliance and quality of life. Relevance to clinical practice These results will allow the inflammatory bowel disease team to develop educational programmes that account for the disease-related knowledge of each patient. Inflammatory bowel disease nurses should evaluate their interventions to provide evidence that educating our patients contributes to improving their treatment outcomes and overall health statuses. [ABSTRACT FROM AUTHOR]

Copyright of Revista Chilena de Cirugia is the property of Sociedad de Cirujanos de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Chilena de Cirugia is the property of Sociedad de Cirujanos de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Chilena de Cirugia is the property of Sociedad de Cirujanos de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Laparoscopic colorectal surgery (LCRS) has several advantages over open surgery, but LCRS has been associated with a higher rate of postoperative complications (POCs) among obese patients [body mass index (BMI), ≥30 kg/m]. The prevalence of obesity in Chile is increasing, up to 25.1 % in 2010, suggesting that a higher percentage of patients undergoing LCRS will be obese. This study compared POC rates between obese and nonobese patients undergoing LCRS. Methods: This study included case and control patients in a prospectively maintained LCRS database who underwent LCRS between July 2007 and June 2012 at Clinica Las Condes, Santiago, Chile. Obese and nonobese (BMI <30 kg/m) patients were paired by gender, age, American Society of Anesthesiologists class, preoperative diagnosis, and type of surgery. Intraoperative complications and POCs were documented up to 30 days. The severity of each POC was classified by Clavien-Dindo score. Results: In this study, 449 patients who underwent LCRS during the study period were identified. The study paired 53 obese patients (mean BMI 33.1 kg/m) with 53 nonobese patients (mean BMI 25.9 kg/m). The median age was 55 years in the obese group and 57 years in the nonobese group, and 60 % of the patients in both groups were men. The findings showed POCs in 13 obese (24.5 %) and 15 nonobese (28.3 %) patients ( p = 0.66). Stratified by severity of POCs, the two groups were similar ( p = 0.62). The two groups did not differ in terms of the median time to the first feeding (1 day each) or the hospital length of stay (4 days each). Similar percentages of patients in the two groups required reoperation ( p = 0.4), intensive care unit (ICU) admission ( p = 0.77), and readmission to the hospital ( p = 0.65) because of POCs. Conclusion: The frequency of POCs after LCRS was no higher among the obese patients than among the nonobese patients. [ABSTRACT FROM AUTHOR]

Copyright of Revista Chilena de Cirugia is the property of Sociedad de Cirujanos de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PURPOSE:. Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer. METHODS:. This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test. RESULTS:. Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489). CONCLUSIONS:. The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival. [ABSTRACT FROM AUTHOR]

Keywords: colorectal cancer; cancer associated fibroblasts; interleukin 33; desmoplasia; epithelial-mesenchymal transition DR and SS performed the immunohistochemistry staining of TMA, JR validated Aperio algorithms and performed histological characterization of TMAs. Colorectal cancer, cancer associated fibroblasts, interleukin 33, desmoplasia, epithelial-mesenchymal transition. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) in the treatment of perineal Crohn's disease (PCD).

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. [ABSTRACT FROM AUTHOR]