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MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29 years (range 31-71) and 49.90 years (range 27-87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.
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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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Screening programs for colorectal cancer (CRC) are standard in most developed countries because they reduce mortality and are cost-effective. Within them, colonoscopy allows to directly visualize the colon and remove neoplastic lesions. However, it is an expensive exam with low adherence in asymptomatic individuals. The fecal occult blood test (FOBT) is a low-cost and risk-free method for the user, which results in a high rate of adherence, explaining its use in most screening programs. This article analyzes the effectiveness of different fecal occult blood tests in screening programs. The main conclusions are that the sensitivity of the guaiac-based chemical test for the detection of colorectal cancer is lower than that observed with qualitative and quantitative immunological tests. Automated quantitative methods allow objective readings independent of the operator and the reaction reading time, necessary for the analysis of large numbers of samples. The participation rate with immunological FOBTs is higher than with chemical ones, which is why they are preferred by the different countries that have screening programs. The use of quantitative tests allows stratification of symptomatic and asymptomatic patients at higher risk, in the screening programs.
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Neoplasias Colorretais , Sangue Oculto , Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Guaiaco , Humanos , Programas de RastreamentoRESUMO
Colorectal cancer (CRC) is the second most frequent neoplasm in Chile and its mortality rate is rising in all ages. However, studies characterizing CRC according to the age of onset are still lacking. This study aimed to identify clinical, pathological, and molecular features of CRC in Chilean patients according to the age of diagnosis: early- (≤50 years; EOCRC), intermediate- (51-69 years; IOCRC), and late-onset (≥70 years; LOCRC). The study included 426 CRC patients from Clinica Las Condes, between 2007 and 2019. A chi-square test was applied to explore associations between age of onset and clinicopathological characteristics. Body Mass Index (BMI) differences according to age of diagnosis was evaluated through t-test. Overall (OS) and cancer-specific survival (CSS) were estimated by the Kaplan-Meier method. We found significant differences between the age of onset, and gender, BMI, family history of cancer, TNM Classification of Malignant Tumors stage, OS, and CSS. EOCRC category was characterized by a family history of cancer, left-sided tumors with a more advanced stage of the disease but better survival at 10 years, and lower microsatellite instability (MSI), with predominant germline mutations. IOCRC has shown clinical similarities with the EOCRC and molecular similarities to the LOCRC, which agrees with other reports.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Chile/epidemiologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Metilação de DNA , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Hereditariedade , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
Colorectal cancer (CRC) is one of the most common cancers worldwide. As with other cancers, CRC is a multifactorial disease due to the combined effect of genetic and environmental factors. Most cases are sporadic, but a small proportion is hereditary, estimated at around 5-10%. In both, the tumor interacts with heterogeneous cell populations, such as endothelial, stromal, and immune cells, secreting different signals (cytokines, chemokines or growth factors) to generate a favorable tumor microenvironment for cancer cell invasion and metastasis. There is ample evidence that inflammatory processes have a role in carcinogenesis and tumor progression in CCR. Different profiles of cell activation of the tumor microenvironment can promote pro or anti-tumor pathways; hence they are studied as a key target for the control of cancer progression. Additionally, the intestinal mucosa is in close contact with a microorganism community, including bacteria, bacteriophages, viruses, archaea, and fungi composing the gut microbiota. Aberrant composition of this microbiota, together with alteration in the diet-derived microbial metabolites content (such as butyrate and polyamines) and environmental compounds has been related to CRC. Some bacteria, such as pks+ Escherichia coli or Fusobacterium nucleatum, are involved in colorectal carcinogenesis through different pathomechanisms including the induction of genetic mutations in epithelial cells and modulation of tumor microenvironment. Epithelial and immune cells from intestinal mucosa have Pattern-recognition receptors and G-protein coupled receptors (receptor of butyrate), suggesting that their activation can be regulated by intestinal microbiota and metabolites. In this review, we discuss how dynamics in the gut microbiota, their metabolites, and tumor microenvironment interplays in sporadic and hereditary CRC, modulating tumor progression.
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Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Suscetibilidade a Doenças , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Microbiota , Microambiente Tumoral , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Neoplasias Colorretais/patologia , Dieta , Metabolismo Energético , Microbioma Gastrointestinal , HumanosRESUMO
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.
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Humanos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Período Pós-Operatório , Seguimentos , Resultado do TratamentoRESUMO
Screening programs for colorectal cancer (CRC) are standard in most developed countries because they reduce mortality and are cost-effective. Within them, colonoscopy allows to directly visualize the colon and remove neoplastic lesions. However, it is an expensive exam with low adherence in asymptomatic individuals. The fecal occult blood test (FOBT) is a low-cost and risk-free method for the user, which results in a high rate of adherence, explaining its use in most screening programs. This article analyzes the effectiveness of different fecal occult blood tests in screening programs. The main conclusions are that the sensitivity of the guaiac-based chemical test for the detection of colorectal cancer is lower than that observed with qualitative and quantitative immunological tests. Automated quantitative methods allow objective readings independent of the operator and the reaction reading time, necessary for the analysis of large numbers of samples. The participation rate with immunological FOBTs is higher than with chemical ones, which is why they are preferred by the different countries that have screening programs. The use of quantitative tests allows stratification of symptomatic and asymptomatic patients at higher risk, in the screening programs.
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Humanos , Neoplasias Colorretais/diagnóstico , Sangue Oculto , Programas de Rastreamento , Colonoscopia , Detecção Precoce de Câncer , GuaiacoRESUMO
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.
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Carcinogênese/genética , Instabilidade Cromossômica/genética , Neoplasias Colorretais/genética , Instabilidade de Microssatélites , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Chile/epidemiologia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Metilação de DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
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.
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Colorectal (CRC) is one of the most common types of cancer worldwide. Most tumors develop from an adenoma in a period of 10 to 15 years, but some may appear without previous adenomatous lesions. Seventy-five percent of colorectal cancers are sporadic, 20% have a family component (first or second-degree relatives with CRC) and 5% have a hereditary predisposition with a Mendelian pattern. The epidemiological evolution in the recent years in Chile has a worrisome evolution and the treatment costs of advanced stages are a burden for the healthcare system. We herein highlight the main Chilean medical and scientific contributions on the pathogenesis, early diagnosis, and treatment of CRC, which lead to its better understanding, and therefore better management, based on local evidence.