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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.
Assuntos
Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Exossomos , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenoma/sangue , Adenoma/patologia , Idoso , Chile , Colo/diagnóstico por imagem , Colo/patologia , Colonoscopia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Feminino , Humanos , Cooperação Internacional , Japão , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Projetos PilotoRESUMO
BACKGROUND: The molecular testing of KRAS mutation status in metastatic colorectal cancer patients is mandatory to identify patients eligible for anti-epidermal growth factor receptor monoclonal antibody therapy. AIM: To report the frequency of KRAS gene mutations in Chilean patients with colorectal cancer (CRC). MATERIAL AND METHODS: A cohort of 262 Chilean patients with CRC aged 26 to 90 years (53% males), was studied. KRAS mutation status was analyzed by real-time polymerase chain reaction and correlated with clinicopathological data. RESULTS: Ninety-eight patients (37%) were positive for KRAS mutations. G12D was the most common mutation with a frequency of 36.7%, followed by G12V (25.5%), G13D (17.3%), G12A (7.1%), G12C (6.1%), G12S (5.1%) and G12R (2%). The frequency of the mutation in left, right colon and rectal tumors was 37.8, 32.6 and 44.9%, respectively. Among tumors with mutations, 86.7% were well or moderately differentiated tumors and the rest were poorly differentiated. No significant associations between KRAS gene mutations and other clinicopathological features of the tumor were observed. CONCLUSIONS: The frequencies of KRAS mutations reported in this study are similar to frequencies reported for European and North-American populations, lower than in a Spanish study and higher than in a Peruvian study.
Assuntos
Neoplasias Colorretais/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Chile/etnologia , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , DNA de Neoplasias/genética , Fator de Crescimento Epidérmico/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras) , Reação em Cadeia da Polimerase em Tempo Real , Fatores SexuaisRESUMO
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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BACKGROUND: Total colectomy is the surgery of choice for colonic inertia (CI) when medical treatment has failed. Laparoscopic total colectomy has demonstrated to be a feasible technique. OBJECTIVE: Present our experience in patients with CI who underwent laparoscopic total colectomy (TC) + ileorectoanastomosis (IRA) and evaluate the functional results and medium-term follow-up after this surgery. MATERIAL AND METHODS: All patients with CI were included in a prospective laparoscopic surgical protocol, from 2002 to 2007. These patients had a complete work-up for chronic constipation (clinical records, barium enema, colonic transit time, defecography, anorectal manometry, small bowel follow through). All patients were evaluated with Wexner's score for constipation pre- and postoperatively, asked if they would recommend surgery to other patients, and if they were satisfied with the procedure (on a scale from 1 to 10). Statistical analysis was carried out using Student's T-test. RESULTS: In this period 20 patients were operated with diagnosis of CI. All patients were females with an average age of 41.5 years (range 18-52 years). Mean operative time was 248 min (range 170-360 min). One (5%) patient was converted to open surgery. The medium time to flatus per anum and feeding was 2 (range 1-6) and 3 (range 2-6) days, respectively. The medium postoperative stay was 7 days. Seven patients (35%) presented surgical postoperative complications (three postoperative ileus, one portal thrombosis, one rectal hemorrhage, one anastomotic leakage, and one hemoperitoneum). There was no postoperative mortality. The average follow-up was 25 months (range 1-60 months). Preoperative Wexner's constipation score was 22.3 (range 19-29 months) pre surgery and at the end of follow-up was 1.8 (range 0-6) (p < 0.01). The medium level of satisfaction was 8 (range 2-10) and only one patient would not recommend surgery to other patients. CONCLUSION: The laparoscopic access is a safe technique with satisfactory functional results after medium-term follow-up.
Assuntos
Colectomia , Constipação Intestinal/cirurgia , Laparoscopia , Adolescente , Adulto , Anastomose Cirúrgica , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Íleo/cirurgia , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Reto/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Background: The molecular testing of KRAS mutation status in metastatic colorectal cancer patients is mandatory to identify patients eligible for anti-epidermal growth factor receptor monoclonal antibody therapy. Aim: To report the frequency of KRAS gene mutations in Chilean patients with colorectal cancer (CRC). Material and Methods: A cohort of 262 Chilean patients with CRC aged 26 to 90 years (53% males), was studied. KRAS mutation status was analyzed by real-time polymerase chain reaction and correlated with clinicopathological data. Results: Ninety-eight patients (37%) were positive for KRAS mutations. G12D was the most common mutation with a frequency of 36.7%, followed by G12V (25.5%), G13D (17.3%), G12A (7.1%), G12C (6.1%), G12S (5.1%) and G12R (2%). The frequency of the mutation in left, right colon and rectal tumors was 37.8, 32.6 and 44.9%, respectively. Among tumors with mutations, 86.7% were well or moderately differentiated tumors and the rest were poorly differentiated. No significant associations between KRAS gene mutations and other clinicopathological features of the tumor were observed. Conclusions: The frequencies of KRAS mutations reported in this study are similar to frequencies reported for European and North-American populations, lower than in a Spanish study and higher than in a Peruvian study.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Colorretais/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Fatores Etários , Chile/etnologia , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , DNA de Neoplasias/genética , Fator de Crescimento Epidérmico/genética , Invasividade Neoplásica/genética , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Fatores SexuaisRESUMO
Introducción: En la actualidad hay consenso en la seguridad oncológica en la cirugía laparoscópica para el tratamiento del cáncer de colon, sin embargo, en el cáncer de recto (CR) los resultados a largo plazo, continúan siendo objeto de estudio. El objetivo de este trabajo es analizar la sobrevida a largo plazo en pacientes operados por adenocarcinoma de recto por vía laparoscópica. Material y Métodos: Desde la base de datos prospectiva de cirugía colorrectal laparoscópica se seleccionaron los pacientes operados por CR en el periodo entre octubre 2000 y diciembre 2009. Se excluyó a los pacientes con cáncer colorrectal hereditario. Se analizaron los datos de seguimiento los cuales son obtenidos mediante registros clínicos y datos del registro civil. Se realizó un análisis de sobrevida con el método de Kaplan-Meier. Resultados: En el periodo mencionado, 60 pacientes fueron operados por CR, 2 (3,4%) pacientes fallecieron en el postoperatorio temprano y fueron excluidos en el análisis de sobrevida, por tanto, 58 pacientes fueron incluidos en el seguimiento. El 41% eran sexo femenino y la edad promedio fue de 60 ± 11,6 años. Los tumores se encontraban localizados en el recto superior, medio e inferior en un 28%, 28% y 44% respectivamente. Las cirugías realizadas fueron resección abdominoperineal, resección anterior ultrabaja interesfintérica, resección anterior ultrabaja y resección anterior baja en un 8%, 28%, 5% y 59% de los pacientes, respectivamente. El 50% de los pacientes recibieron neoadyuvancia. Tras la estadificación postoperatoria 4% fueron clasificados estadio 0, 38% estadio I, 17% estadio II, 28% estadio III y 13% estadio IV. El recuento de linfonodos de la pieza operatoria fue de 12,3 en promedio. A un seguimiento de 42,6 meses (r: 17 a 103 meses) la sobrevida global estimada a 5 años es de 85%. Según estadios la sobrevida estimada a 5 años fue de 100% para el estadio 0 y I, 88% para el estadio II, 74% para el estadio III... (TRUNCADO)
Background: Currently there is a consensus in oncological safety for laparoscopic surgery for colon cancer; however, in rectal cancer long term outcomes are still a subject of debate. The aim is to analyze long term survival in patients who underwent laparoscopic surgery for rectal cancer. Material and Methods: From the prospective database of laparoscopic colorectal surgery, we selected patients operated on between October 2000 and December 2009. Patients with hereditary colorectal cancer were excluded. Follow-up data was obtained by medical records and national vital records. Survival was analyzed using the Kaplan-Meier method. Results: In this period, 60 patients were operated on for rectal cancer. Two died in the early postoperative period and were excluded from the analysis; therefore, 58 patients were included in follow-up. Forty-one percent were female and mean age was 60±11.6 years old. Tumors were localized in the upper, mid and lower rectum in 28%, 28% and 44%, respectively. Surgeries performed were abdominoperineal resection, ultra-low intersphincteric resection, ultralow anterior resection and low anterior resection in 8%, 28%, 5% and 59% of patients, respectively. Fifty percent received neoadjuvant treatment. After postoperative staging 4% were classified as stage 0,17% as stage I, 28% as stage II, 28% as stage III, and 13% as stage IV. At a mean 42.6 month follow-up (r: 17-103 months) estimated overall 5-year survival was 85%. When analyzed according to stage, estimated overall 5-year survival was 100% for stages 0 and I, 88% for stage II, 74% for stage III, and 57% for stage IV. Conclusion: Long term survival in patients undergoing laparoscopic surgery for rectal cancer is satisfactory and is within the values reported by international centers.