RESUMO
A national colorectal cancer (CRC) screening program began in Chile in 2012, which is an international collaboration between Japan and Chile and is based on a standardized protocol supported by Tokyo Medical and Dental University. We describe the results from the first 2 years of screening at one public hospital in Punta Arenas, Chile. Of 4124 asymptomatic individuals aged between 50 and 75 years, 485 participants with immunological fecal occult blood test values of at least 100 ng/ml and/or those with family histories of CRC underwent colonoscopies. Lesions were found in 291 participants, and 642 histologic samples were obtained. Chilean pathologists made the initial histologic diagnoses, and a Japanese pathologist reviewed the histologic slides and analyzed the results. Of the 291 participants with lesions, 60 (20.6%) were diagnosed with adenocarcinomas, of which 50 (83.3%) were early-phase adenocarcinomas (pTis or pT1), and 163 (56.0%) were diagnosed with conventional adenomas, of which 96 (58.9%) were high-risk adenomas. The cancer prevalence within the screened population was 1.5% (60 of 4124). The colonoscopy cancer detection rate was 12.4% (60 of 485). Notably, we detected one flat-depressed (0-IIc) lesion that measured 5 mm and had invaded the submucosa. The findings from this screening program are the first to show the histopathologic distributions of consecutive lesions and the high incidence of CRC in Chile. The high detection rates for high-risk adenomas and cancer support the feasibility of early CRC screening and its potential to reduce the mortality associated with CRC.
Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Cooperação Internacional , Programas de Rastreamento/estatística & dados numéricos , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adenocarcinoma/prevenção & controle , Idoso , Chile/epidemiologia , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Estudos de Viabilidade , Feminino , Humanos , Incidência , Japão , Masculino , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Sangue Oculto , PrevalênciaRESUMO
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: Colorectal Cancer Screening Programs (CRCSP) are widely accepted in developed countries. Unfortunately, financial restrictions, low adherence rate and variability on colonoscopy standardization hamper the implementation of CRCSP in developing countries. AIM: To analyze a multicentric pilot model of CRCSP in Chile. MATERIAL AND METHODS: A prospective model of CRCSP was carried out in three cities, from 2012 to 2015. The model was based on CRC risk assessment and patient education. Health care personnel were trained about logistics and protocols. The endoscopy team was trained about colonoscopy standards. A registered nurse was the coordinator in each center. We screened asymptomatic population aged between 50 and 75 years. Immunological fecal occult blood test (FIT) was offered to all participants. Subjects with positive FIT underwent colonoscopy. RESULTS: A total of 12,668 individuals were enrolled, with a FIT compliance rate of 93.9% and 2,358 colonoscopies were performed. Two hundred and fifty high-risk adenomas and 110 cancer cases were diagnosed. One patient died before treatment due to cardiovascular disease, 74 patients (67%) underwent endoscopic resection and 35 had surgical treatment. Ninety one percent of patients had an early stage CRC (0-I-II). Among colonoscopy indicators, 80% of cases had an adequate bowel preparation (Boston > 6), cecal intubation rate was 97.7%, adenoma detection rate was 36.5%, and in 94.5% of colonoscopies, withdrawal time was adequate (> 8 min). CONCLUSIONS: This CRCS pilot model was associated to a high rate of FIT return and colonoscopy quality standards. Most CRCs detected with the program were treated by endoscopic resection.
Assuntos
Adenoma/diagnóstico , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Avaliação de Programas e Projetos de Saúde , Medição de Risco/métodos , Adenoma/patologia , Idoso , Análise de Variância , Chile , Colonoscopia/normas , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Sangue Oculto , Educação de Pacientes como Assunto , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
Background: Colorectal Cancer Screening Programs (CRCSP) are widely accepted in developed countries. Unfortunately, financial restrictions, low adherence rate and variability on colonoscopy standardization hamper the implementation of CRCSP in developing countries. Aim: To analyze a multicentric pilot model of CRCSP in Chile. Material and Methods: A prospective model of CRCSP was carried out in three cities, from 2012 to 2015. The model was based on CRC risk assessment and patient education. Health care personnel were trained about logistics and protocols. The endoscopy team was trained about colonoscopy standards. A registered nurse was the coordinator in each center. We screened asymptomatic population aged between 50 and 75 years. Immunological fecal occult blood test (FIT) was offered to all participants. Subjects with positive FIT underwent colonoscopy. Results: A total of 12,668 individuals were enrolled, with a FIT compliance rate of 93.9% and 2,358 colonoscopies were performed. Two hundred and fifty high-risk adenomas and 110 cancer cases were diagnosed. One patient died before treatment due to cardiovascular disease, 74 patients (67%) underwent endoscopic resection and 35 had surgical treatment. Ninety one percent of patients had an early stage CRC (0-I-II). Among colonoscopy indicators, 80% of cases had an adequate bowel preparation (Boston > 6), cecal intubation rate was 97.7%, adenoma detection rate was 36.5%, and in 94.5% of colonoscopies, withdrawal time was adequate (> 8 min). Conclusions: This CRCS pilot model was associated to a high rate of FIT return and colonoscopy quality standards. Most CRCs detected with the program were treated by endoscopic resection.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/diagnóstico , Avaliação de Programas e Projetos de Saúde , Adenoma/diagnóstico , Colonoscopia/métodos , Medição de Risco/métodos , Detecção Precoce de Câncer/métodos , Neoplasias Colorretais/patologia , Adenoma/patologia , Chile , Projetos Piloto , Estado Nutricional , Educação de Pacientes como Assunto , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Análise de Variância , Colonoscopia/normas , Detecção Precoce de Câncer/normas , Sangue OcultoRESUMO
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.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptores ErbB/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Chile , Análise Mutacional de DNA , Feminino , Genes erbB-1 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Transdução de Sinais/genética , Análise Serial de Tecidos , TranscriptomaRESUMO
BACKGROUND: In Chile, mortality from colorectal cancer (CRC) has increased rapidly. To help address this issue, the Prevention Project for Neoplasia of the Colon and Rectum (PRENEC) program was initiated in 2012 with intensive support from Tokyo Medical and Dental University (TMDU) in Tokyo, Japan, as part of an international collaboration. METHODS: From June 2012 to July 2014, a total of 10,575 asymptomatic participants were enrolled in PRENEC. Participants with positive immunochemical fecal occult blood test (iFOBT) results or a family history of CRC underwent colonoscopy. The colonoscopy results from a similar, previous project in Chile (PREVICOLON) were compared with those from PRENEC. Furthermore, the initial colonoscopies of 1562 participants in PRENEC were analyzed according to whether the colonoscopists were from TMDU or Chile. RESULTS: The complete colonoscopy, adenoma detection, and cancer detection rates were 88.0%, 26.7%, and 1.1%, respectively, in PREVICOLON, while the corresponding values were 94.4%, 41.8%, and 6.0%, respectively, in PRENEC. In PRENEC, 107 cases of CRC were detected, amounting for 1.0% of all participants. Considering initial colonoscopies in PRENEC, the complete colonoscopy, adenoma detection, and cancer detection rates were 97.4%, 45.3%, and 9.3%, respectively, for physicians at TMDU and 93.3%, 41.5%, and 5.1%, respectively for Chilean physicians. The detection rates of intramucosal cancer were 7.3% and 3.7%, respectively, for TMDU and Chilean physicians. CONCLUSIONS: Quality indicators of colonoscopy substantially improved from PREVICOLON to PRENEC. The assessments made by Chilean physicians alone were improved in PRENEC, but remained better in the TMDU group. Moreover, physicians from TMDU detected more CRCs than Chilean physicians, especially at earlier stages.
Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Chile , Comportamento Cooperativo , Detecção Precoce de Câncer/métodos , Feminino , Saúde Global , Humanos , Cooperação Internacional , Japão , Masculino , Programas de Rastreamento , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: Several lines of clinical evidence support the concept that the reduction of blood pressure may be useful in the prevention of diabetic kidney disease. In young diabetic spontaneously hypertensive rats (SHR), prevention of hypertension reduces several early renal abnormalities including albuminuria. However, the contribution of nephrin loss to albuminuria in this early stage of experimental diabetes is unknown. Therefore, we investigated whether elevation of albuminuria in young diabetic SHR is associated with nephrin loss, and if prevention of hypertension, with or without inhibition of the renin-angiotensin system, precludes these abnormalities. METHODS: Diabetes was induced by streptozotocin injection in 4-week-old still normotensive SHR and their genetically normotensive control, Wistar-Kyoto rats. Diabetic SHR were randomized for no treatment, or treatment with captopril, losartan, or triple therapy (hydrochlorothiazide, reserpine and hydralazine) for 20 days. RESULTS: The increase in systolic blood pressure was equally prevented by all treatments. Albuminuria was higher in diabetic SHR and similarly reduced (p < 0.05) by captopril, losartan, and triple therapy. Glomerular expression of nephrin was significantly reduced in diabetic SHR in comparison with non-diabetic controls. The antihypertensive treatment prevented the reduction in glomerular expression of nephrin. CONCLUSIONS: These results demonstrate that the loss of nephrin is associated with albuminuria in a model of genetic hypertension and diabetes, and that the prevention of development of hypertension restores nephrin and prevents albuminuria. This finding suggests a crucial role of blood pressure in diabetes as determinant of nephrin expression and albuminuria.