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2.
Adv Exp Med Biol ; 1268: 39-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918213

RESUMO

Over the last several decades, extensive research on vitamin D and its role on cancer incidence, cancer survival (survival or mortality from cancer among individuals diagnosed with cancer), and cancer mortality (fatal cases occurring during the study period in an initially cancer-free population) has been conducted. A variety of study designs were implemented to explore vitamin D status, assessed by measuring sun exposure, vitamin D intake, and circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although not many randomized controlled trials have examined the relationship between vitamin D and cancer incidence, observational studies have consistently shown a protective association between vitamin D and cancer incidence, especially for colorectal cancer. In addition, randomized controlled trials and most observational studies suggested that vitamin D plays a role in reducing cancer mortality. The potential benefit of vitamin D on cancer mortality may operate during the pre-diagnostic stages by affecting late-stage tumor progression and metastatic seeding, during the treatment phase by complementing or enhancing effects of therapies, or during the post-diagnostic stages. However, further studies are needed to confirm these conclusions, establish the optimal dosage and timing of vitamin D intakes for the most benefit, find which cancer types are affected, and understand the underlying mechanisms.


Assuntos
Neoplasias/epidemiologia , Neoplasias/mortalidade , Vitamina D , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Progressão da Doença , Humanos , Incidência , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitaminas/administração & dosagem , Vitaminas/sangue
3.
Am J Hum Genet ; 107(3): 432-444, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758450

RESUMO

Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.


Assuntos
Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Genoma Humano/genética , Medição de Risco , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Teorema de Bayes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
4.
PLoS One ; 15(8): e0236569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756596

RESUMO

BACKGROUND: The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases. METHODS: Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. RESULTS: Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33). CONCLUSION: The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Carcinoembrionário/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Intervalo Livre de Progressão
5.
Ann R Coll Surg Engl ; 102(7): 504-509, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32799666

RESUMO

INTRODUCTION: The aim of the study was to establish the natural history of elderly patients with non-metastatic colorectal cancer who underwent non-operative management in comparison with those who underwent operative management. MATERIALS AND METHODS: A retrospective analysis of patients aged 80 years and above diagnosed with colorectal cancer between 2007 and 2015 in a tertiary care hospital in the Southwest of England was done. Patients were divided into non-operatively managed and operatively managed groups. Clinical demographics, Charlson Comorbidity Index, location of the tumour and overall survival between the two groups were compared. RESULTS: A total of 407 patients were studied; 132 were treated non-operatively and 275 operatively. The non-operative group included fewer right-sided colon cancers (28.7% vs 54.9%), but significantly more rectal cancers were managed non-operatively (43.9 vs 23.6%, respectively). The two and five year overall survival was 38.9% and 11.3% respectively in the non-operative group, significantly lower than patients in the operative group where the two and five year survival was 78.9% and 59.6% respectively (p = .0001). The median Charlson Comorbidity Index was 7.99 for the non-operative group and 7.49 in the operative group (p = 0.109). Patients treated non-operatively were deemed unfit without objective frailty assessment and only 43/132(32.6%) had formal anaesthetic assessment before being deemed unfit for surgery. CONCLUSION: The survival of octa- and nonagenarians with non-metastatic colorectal cancer managed conservatively is significantly less than counterparts managed operatively. Our present strategy of deciding and denying treatment of the elderly patient with colorectal cancer is arbitrary, highlighting the need for robust geriatric and frailty assessment.


Assuntos
Neoplasias Colorretais/terapia , Tratamento Conservador/métodos , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências
6.
Yonsei Med J ; 61(7): 579-586, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32608201

RESUMO

PURPOSE: The impact of changes in body mass index and waist circumference on the development of metachronous colorectal neoplasia (CRN) after polypectomy has rarely been examined. We evaluated the association between changes in overall/abdominal obesity and metachronous CRN risk. MATERIALS AND METHODS: We studied patients who underwent ≥1 adenoma removal and surveillance colonoscopy. Patients were classified into the following four groups based on the changes in overall obesity from index to follow-up colonoscopy: non-obesity persisted (group 1), obesity to non-obesity (group 2), non-obesity to obesity (group 3), and obesity persisted (group 4). Patients were also divided into another four groups based on similar changes in abdominal obesity (groups 5-8). RESULTS: The number of patients in groups 1, 2, 3, and 4 was 5074, 457, 643, and 3538, respectively, and that in groups 5, 6, 7, and 8 was 4229, 538, 656, and 2189, respectively. Group 4 had a significantly higher risk of metachronous CRN compared to groups 1 and 2. However, metachronous advanced CRN (ACRN) risk was not different among groups 1, 2, 3, and 4. Metachronous CRN risk in group 8 (abdominal obesity persisted) was higher than that in groups 5 (non-abdominal obesity persisted) and 7 (non-abdominal obesity to abdominal obesity), and tended to be higher than that in group 6 (abdominal obesity to non-abdominal obesity). Additionally, group 8 had a significantly higher risk of metachronous ACRN compared to groups 5, 6, and 7. CONCLUSION: Changes in obesity affected the metachronous CRN risk. In particular, changes in abdominal obesity affected the metachronous ACRN risk.


Assuntos
Pólipos do Colo/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/patologia , Segunda Neoplasia Primária/patologia , Obesidade Abdominal/complicações , Obesidade/complicações , Adulto , Índice de Massa Corporal , Pólipos do Colo/epidemiologia , Pólipos do Colo/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/cirurgia , Obesidade/epidemiologia , Obesidade Abdominal/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Circunferência da Cintura/fisiologia
7.
Arq Gastroenterol ; 57(2): 182-187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609160

RESUMO

BACKGROUND: Colorectal cancer is a serious public health problem and one of the most common cancer worldwide. Countries around the world have shown different trends. While incidence and mortality rates for colorectal cancer are on an upward trend in developing countries, these rates have been on a downward trend in most developed countries. OBJECTIVE: To analyze the temporal trend of morbimortality by colorectal cancer in Brazil between 2002 and 2016. METHODS: Descriptive, time series research. Data were extracted from the national information systems for hospitalizations and deaths of the respective years. RESULTS: There were increasing trends in hospital morbidity and mortality from colorectal cancer in all regions of the country, with the very elderly individuals dying at a higher rate. Women (52.1%) were more affected than men, but death rates were higher for males aged 60 years or more. Regional disparities were evident, with almost 80% of deaths occurring in the South and Southeast, with the largest annual increase in the South and the lowest in the North. Regarding hospitalization, South and Southeast presented higher annual growths. CONCLUSION: These data add knowledge about the profile of public hospitalizations and deaths, reaffirming that colorectal cancer contributes to an important burden of disease and mortality in Brazil. These elements have implications for the review of colorectal cancer prevention and control strategies, as well as for public health investments.


Assuntos
Neoplasias Colorretais/epidemiologia , Saúde Pública , Idoso , Brasil/epidemiologia , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Morbidade
8.
Arq Gastroenterol ; 57(2): 193-197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609162

RESUMO

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) has emerged as a revolutionary method allowing resection of colorectal lesions without submucosal injection. Brazilian literature about this technique is sparse. OBJECTIVE: The aim of this study was evaluate the efficacy and safety of UEMR technique for removing non-pedunculated colorectal lesions in two Brazilian tertiary centers. METHODS: This prospective study was conducted between June 2016 and May 2017. Naïve and non-pedunculated lesions without signs of submucosal invasion were resected using UEMR technique. RESULTS: A total of 55 patients with 65 lesions were included. All lesions, except one, were successfully and completely removed by UEMR (success rate 98.5%). During UEMR, two cases of bleeding were observed (3.0%). One patient had abdominal pain on the day after resection without pneumoperitoneum. There was no perforation or delayed bleeding. CONCLUSION: This study supports the existing data indicating acceptable rates of technical success, and low incidence of adverse events with UEMR. The results of this Brazilian study were consistent with previous abroad studies.


Assuntos
Neoplasias Colorretais/epidemiologia , Ressecção Endoscópica de Mucosa/métodos , Brasil , Colonoscopia , Humanos , Mucosa Intestinal , Estudos Prospectivos , Resultado do Tratamento
9.
Arq Bras Cir Dig ; 33(1): e1500, 2020 Jul 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32667530

RESUMO

BACKGROUND: One of the most important concerns on health is the increased rates of obesity in population and the speed in which this number is increasing. This number translates a serious public health problem, since it also increases the risk of several other diseases associated with obesity resulting in significant morbidity and mortality. Among them, it seems to be connected to several neoplasms, such as colorectal carcinoma. AIM: To evaluate the impact of obesity as a risk factor for colorectal carcinoma through the detection of adenoma, and to discuss the mechanisms that could establish a link between obesity and neoplasm. METHODS: Patients who underwent colonoscopy were included. Personal and anthropometric data, clinical history, and results of the tests were analyzed in order to verify the correlation of BMI and the presence of adenomatous polyps. RESULTS: A total of 142 patients were studied, which a mean age of 62 years. Of the patients, 74 (52.1%) were men and 68 (47.9%) were. Obesity was identified in 16.2% of the patients. Polyps were found in 61 (42.9%), mostly smaller than 1 cm. Obese individuals were 1.56 times more likely to present colorectal adenoma than patients with normal weight. CONCLUSION: This study, although showing the greater presence of colorectal adenomas in obese individuals, did not show a significant difference in the occurrence of pre-malignant lesions.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Pólipos Adenomatosos , Pólipos do Colo , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Fatores de Risco
10.
Am J Gastroenterol ; 115(7): 1103-1109, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618661

RESUMO

INTRODUCTION: Diabetes mellitus (DM) and colorectal cancer (CRC) share some risk factors, including lifestyle and metabolic disturbances. We aimed to provide in-depth information on the association of CRC risk, especially early-onset CRC, with DM, family history of CRC, and age at DM diagnosis. METHODS: A nationwide cohort study was conducted using Swedish family cancer data sets, inpatient, and outpatient registers (follow-up: 1964-2015), including all individuals born after 1931 and their parents (12,614,256 individuals; 559,375 diabetic patients; 162,226 CRC patients). RESULTS: DM diagnosis before the age of 50 years was associated with a 1.9-fold increased risk of CRC before the age of 50 years (95% CI for standardized incidence ratio: 1.6-2.3) vs 1.3-fold risk of CRC at/after the age of 50 years (1.2-1.4). DM diagnosis before the age of 50 years in those with a family history of CRC was associated with 6.9-fold risk of CRC before the age of 50 years (4.1-12) and 1.9-fold risk of CRC at/after the age of 50 years (1.4-2.5). Diabetic patients had a similar lifetime risk of CRC before the age of 50 years (0.4%, 95% CI: 0.3%-0.4%) to those with only a family history of CRC (0.5%, 0.5%-0.5%), double that of the population (0.2%, 0.2%-0.2%). DISCUSSION: Our large cohort with valid information on DM and family history of cancer showed that DM is associated with increased risk of CRC in a magnitude close to having family history of CRC. Associations of DM and CRC family history with increased CRC risk were most prominent in young adults. These findings warrant further studies on harms, benefits, and cost-effectiveness of CRC screening in patients with diabetes, especially type 2, at earlier ages than in the general population.


Assuntos
Neoplasias Colorretais/genética , Diabetes Mellitus/genética , Adulto , Idoso , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Fatores de Risco , Suécia/epidemiologia
11.
Zhonghua Wai Ke Za Zhi ; 58(8): 561-585, 2020 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-32727186

RESUMO

Colorectal cancer (CRC) is one of the most common malignant tumors in China. In recent years, the incidence and mortality of CRC in China have been on the rise. According to the China cancer statistics report in 2018, the incidence and mortality of CRC in China ranked the third and fifth among all malignant tumors, with 376,000 new cases and 191,000 deaths. China has become the country with the highest number of new cases and deaths of CRC every year in the world, which seriously threatens the health of Chinese residents. In 2010, the National Ministry of Health organized colorectal cancer expertise of the Chinese Medical Association to write the Chinese Protocol of Diagnosis and Treatment of Colorectal Cancer (2010 edition) and publish it publicly. Since 2010, the National Health and Family Planning Commission has organized experts to revise the protocol in 2015 and 2017, while the National Health Commission revised it in 2020. The revised part of Chinese Protocol of Diagnosis and Treatment of Colorectal Cancer (2020 edition) involves new progress in the field of imaging examination, pathological evaluation, surgery, chemotherapy and radiotherapy. The 2020 edition of the protocol not only referred to the contents of the international guidelines, but also combined with the specific national conditions and clinical practice in China, and also included many evidence-based clinical data in China recently. The 2020 edition of the protocol would further promote the standardization of diagnosis and treatment of CRC in China, improve the survival and prognosis of patients, and benefit millions of CRC patients and their families.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Guias de Prática Clínica como Assunto , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Humanos
12.
Tumour Biol ; 42(7): 1010428320938492, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32635826

RESUMO

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.


Assuntos
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)/genética
13.
Am Surg ; 86(5): 480-485, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32684047

RESUMO

BACKGROUND: CD24 is a sialoglycoprotein anchored to the cell surface via glycosylphosphatidylinositol and is involved in intracellular signaling processes. It plays an important role in the early stages of the multistep process of colorectal carcinogenesis. Several single nucleotide polymorphisms in the CD24 gene are reported to exert a diverse effect on cancer risk. We aimed to elucidate whether CD24 TG/del genetic variants are associated with susceptibility to colorectal cancer (CRC). METHODS: The study included 179 subjects, 36 with CRC (prior to surgery) and 143 healthy control subjects. Deoxyribonucleic acid was purified from peripheral blood leukocytes, and by using restriction fragment length polymorphism analysis, the CD24 gene was genotyped for the specific genetic variant, TG deletion. Additionally, CD24 protein expression levels were determined by Western blotting analysis. RESULTS: The incidence of the TG/del was higher among the CRC patients compared with healthy controls, 14% and 10%, respectively (P = .54). CD24 protein levels were significantly higher among CRC patients. There were no significant differences in CD24 expression between CRC patients at different stages of the disease or between patients who carry the mutation and those who did not. CONCLUSIONS: CD24 genetic variant might be of clinical value for risk assessment as part of cancer prevention programs. Further study on larger populations is needed to validate the importance of this dinucleotide deletion in CRC development. Overexpression of CD24 protein occurs early along the multistep process of CRC carcinogenesis, and a simple blood sample based on CD24 expression on peripheral blood leukocytes can contribute to early diagnosis.


Assuntos
Antígeno CD24/genética , Neoplasias Colorretais/genética , Deleção de Genes , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Feminino , Variação Genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
14.
PLoS One ; 15(7): e0235409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726314

RESUMO

OBJECTIVES: To identify inequalities in cancer survival rates for patients with a history of severe psychiatric illness (SPI) compared to those with no history of mental illness and explore differences in the provision of recommended cancer treatment as a potential explanation. DESIGN: Population-based retrospective cohort study using linked cancer registry and administrative data at ICES. SETTING: The universal healthcare system in Ontario, Canada. PARTICIPANTS: Colorectal cancer (CRC) patients diagnosed between April 1st, 2007 and December 31st, 2012. SPI history (schizophrenia, schizoaffective disorders, other psychotic disorders, bipolar disorders or major depressive disorders) was determined using hospitalization, emergency department, and psychiatrist visit data and categorized as 'no history of mental illness, 'outpatient SPI history', and 'inpatient SPI history'. MAIN OUTCOME MEASURES: Cancer-specific survival, non-receipt of surgical resection, and non-receipt of adjuvant chemotherapy or radiation. RESULTS: 24,507 CRC patients were included; 482 (2.0%) had an outpatient SPI history and 258 (1.0%) had an inpatient SPI history. Individuals with an SPI history had significantly lower survival rates and were significantly less likely to receive guideline recommended treatment than CRC patients with no history of mental illness. The adjusted HR for cancer-specific death was 1.69 times higher for individuals with an inpatient SPI (95% CI 1.36-2.09) and 1.24 times higher for individuals with an outpatient SPI history (95% CI 1.04-1.48). Stage II and III CRC patients with an inpatient SPI history were 2.15 times less likely (95% CI 1.07-4.33) to receive potentially curative surgical resection and 2.07 times less likely (95% CI 1.72-2.50) to receive adjuvant radiation or chemotherapy. These findings were consistent across multiple sensitivity analyses. CONCLUSIONS: Individuals with an SPI history experience inequalities in colorectal cancer care and survival within a universal healthcare system. Increasing advocacy and the availability of resources to support individuals with an SPI within the cancer system are warranted to reduce the potential for unnecessary harm.


Assuntos
Transtorno Bipolar/terapia , Neoplasias Colorretais/terapia , Transtorno Depressivo Maior/terapia , Esquizofrenia/terapia , Adulto , Transtorno Bipolar/complicações , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/patologia , Sobreviventes de Câncer/psicologia , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/patologia , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Pacientes Internados/psicologia , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Esquizofrenia/patologia
15.
PLoS One ; 15(7): e0235038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609729

RESUMO

Lynch syndrome (LS) is an autosomal dominant condition caused by pathogenic variants in mismatch repair (MMR) genes that predispose individuals to different malignancies, such as colorectal cancer (CRC) and endometrial cancer. Current guidelines recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. Economic evaluations in support of such approach, however, are not available in Italy. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the Italian National Health System. Three testing strategies: the sequencing of all MMR genes without prior tumor analysis (Strategy 1), a sequential IHC and MS-MLPA analysis (Strategy 2), and an age-targeted strategy with a revised Bethesda criteria assessment before IHC and methylation-specific MLPA for patients ≥ than 70 years old (Strategy 3) were analyzed and compared to the "no testing" strategy. Quality Adjusted Life Years (QALYs) in relatives after colonoscopy, aspirin prophylaxis and an intensive gynecological surveillance were estimated through a Markov model. Assuming a CRC incidence rate of 0.09% and a share of patients affected by LS equal to 2.81%, the number of detected pathogenic variants among CRC cases ranges, in a given year, between 910 and 1167 depending on the testing strategy employed. The testing strategies investigated, provided one-time to the entire eligible population (CRC patients), were associated with an overall cost ranging between €1,753,059.93-€10,388,000.00. The incremental cost-effectiveness ratios of the Markov model ranged from €941.24 /QALY to €1,681.93 /QALY, thus supporting that "universal testing" versus "no testing" is cost-effective, but not necessarily in comparison with age-targeted strategies. This is the first economic evaluation on different testing strategies for LS in Italy. The results might support the introduction of cost-effective recommendations for LS screening in Italy.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais/diagnóstico , Testes Genéticos/economia , Neoplasias Colorretais/economia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/economia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Análise Custo-Benefício , Reparo de Erro de Pareamento de DNA , Testes Genéticos/métodos , Humanos , Itália/epidemiologia , Proteína 1 Homóloga a MutL/genética , Linhagem , Probabilidade , Anos de Vida Ajustados por Qualidade de Vida
16.
Eur J Endocrinol ; 183(4): D1-D13, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698136

RESUMO

The literature on an association between acromegaly and cancer is particularly abundant on either colorectal cancer or thyroid cancer, and an endless debate is ongoing whether patients with acromegaly should be submitted to specific oncology screening and surveillance protocols. The aim of the present work is to review the most recent data on the risk of either colorectal cancer or thyroid cancer in acromegaly and discuss the opportunity for specific screening in relation to the accepted procedures in the general population.


Assuntos
Acromegalia/complicações , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Programas de Rastreamento , Monitorização Fisiológica , Neoplasias da Glândula Tireoide/diagnóstico , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/terapia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Endocrinologia/métodos , Endocrinologia/normas , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Oncologia/métodos , Oncologia/normas , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Vigilância da População/métodos , Guias de Prática Clínica como Assunto/normas , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/epidemiologia
17.
PLoS One ; 15(7): e0235490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628708

RESUMO

Mutations in KRAS, NRAS, and BRAF (RAS/BRAF) genes are the main predictive biomarkers for the response to anti-EGFR monoclonal antibodies (MAbs) targeted therapy in metastatic colorectal cancer (mCRC). This retrospective study aimed to report the mutational status prevalence of these genes, explore their possible associations with clinicopathological features, and build and validate a predictive model. To achieve these objectives, 500 mCRC Mexican patients were screened for clinically relevant mutations in RAS/BRAF genes. Fifty-two percent of these specimens harbored clinically relevant mutations in at least one screened gene. Among these, 86% had a mutation in KRAS, 7% in NRAS, 6% in BRAF, and 2% in both NRAS and BRAF. Only tumor location in the proximal colon exhibited a significant correlation with KRAS and BRAF mutational status (p-value = 0.0414 and 0.0065, respectively). Further t-SNE analyses were made to 191 specimens to reveal patterns among patients with clinical parameters and KRAS mutational status. Then, directed by the results from classical statistical tests and t-SNE analysis, neural network models utilized entity embeddings to learn patterns and build predictive models using a minimal number of trainable parameters. This study could be the first step in the prediction for RAS/BRAF mutational status from tumoral features and could lead the way to a more detailed and more diverse dataset that could benefit from machine learning methods.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Modelos Estatísticos , Taxa de Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Redes Neurais de Computação , Estudos Retrospectivos
18.
Public Health ; 185: 153-158, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32634606

RESUMO

OBJECTIVES: Colorectal cancer (CRC) remains a major health burden. Although screening is recommended and considered beneficial, further data on its positive effects are needed for worldwide implementation. STUDY DESIGN: The aim of our national multicentre prospective observational study was to reveal and document clinicopathological differences in CRC diagnosed by screening and presented by disease symptoms as well as assess the efficiency of the screening programme in the Czech Republic. METHODS: Between March 2013 and September 2015, a total of 265 patients were enrolled in 12 gastroenterology centres across the Czech Republic. Patients were divided into screening and symptomatic groups and compared for pathology status and clinical characteristics. Screening was defined as a primary screening colonoscopy or a colonoscopy after a positive faecal occult blood test in an average-risk population. RESULTS: The distribution of CRC stages was significantly (statistically and clinically) favourable in the screening group (predominance of stages 0, I and II) compared with the non-screening group (P < 0.001). The presence of distant and local metastases was significantly less frequent in the screening group than in the symptomatic group (P < 0.001). Patients in the screening group had a higher probability of radical surgery (R0) than those diagnosed based on symptoms (P < 0.001). Systemic palliative treatment was indicated in two patients in the screening group compared with 23 patients in the non-screening group (P = 0.018). CONCLUSION: CRC diagnosed by screening disclosed less advanced clinicopathological characteristics and results in patients with a higher probability of radical surgery (R0) than diagnoses established based on symptoms, with subsequent management differing accordingly between both groups. These results advocate the implementation of a suitable worldwide screening programme.


Assuntos
Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer , Programas de Rastreamento/métodos , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , República Tcheca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença
19.
Medicine (Baltimore) ; 99(22): e20185, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481383

RESUMO

The risk of colorectal cancer associated to antidepressant use remains unclear. The purpose of this meta-analysis was to investigate the risk of colorectal cancer associated to antidepressant use.Medline, Embase, Web of Science, and Cochrane Database were accessed from the dates of their establishment to October 2018, to collect study of antidepressant use and colorectal cancer morbidity and mortality. Then a meta-analysis was conducted using Stata 12.0 software.A total of 11 publications involving 109,506 participants were included. The meta-analysis showed that antidepressant use was not associated with colorectal cancer morbidity (relevant risk (RR): 0.97; 95% confidence interval (CI): 0.94-1.01) and mortality (RR: 1.08; 95% CI: 0.99-1.17). Subgroup analysis showed selective serotonin reuptake inhibitor (RR: 0.99; 95% CI: 0.96-1.03) or serotonin norepinephrine reuptake inhibitor (RR: 1.04; 95% CI: 0.86-1.26) were not associated with colorectal cancer risk; however, TCA was associated with colorectal cancer risk decrement (RR: 0.92; 95% CI: 0.87-0.98). Furthermore, the results also showed that antidepressant use was not associated with colorectal cancer risk in Europe and North America (RR: 0.97; 95% CI: 0.92-1.02) and Asia (RR: 1.00; 95% CI: 0.95-1.26). Additionally, a dose-response showed per 1 year of duration of antidepressant use incremental increase was not associated with colorectal cancer risk (RR: 0.96; 95% CI: 0.87-1.09).Evidence suggests that antidepressant use was not associated with colorectal cancer morbidity and mortality. The cumulative duration of antidepressant use did not utilized played critical roles.


Assuntos
Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Neoplasias Colorretais/epidemiologia , Transtorno Depressivo/tratamento farmacológico , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/psicologia , Relação Dose-Resposta a Droga , Humanos , Fatores de Risco , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos
20.
Medicine (Baltimore) ; 99(21): e20238, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481300

RESUMO

OBJECTS: The present study aimed to identify the clinicopathological characteristics of colorectal cancer (CRC) with invasive micropapillary components (IMPCs) and the relationship between different amounts of micropapillary components and lymph node metastasis. METHODS: A cohort of 363 patients with CRC who underwent surgical treatment in the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2013 and December 2016 were retrospectively reviewed. We compared the clinicopathological characteristics, including survival outcomes and immunohistochemical profiles (EMA, MUC1, MLH1, MSH2, MSH6, and PMS2), between CRC with IMPCs and those with conventional adenocarcinoma (named non-IMPCs in this study). Logistic regression was used to identify the association between IMPCs and lymph node invasion. A multivariate analysis was performed using the Cox proportional hazard model to evaluate significant survival predictors. RESULTS: Among 363 patients, 76 cases had IMPCs, including 22 cases with a lower proportion of IMPCs (≤5%, IMPCs-L) and 54 cases with a higher proportion (>5%, IMPCs-H). Compared to the non-IMPC group, the IMPC group (including both IMPC-L and IMPC-H) had a lower degree of tumor differentiation (P = .000), a higher N-classification (P = .000), more venous invasion (P = .019), more perineural invasion (P = .025) and a later tumor node metastasis (TNM) stage (P = .000). Only tumor differentiation (P = .031) and tumor size (P = .022) were different between IMPCs-L and IMPCs-H. EMA/MUC1 enhanced the characteristic inside-out staining pattern of IMPCs, whereas non-IMPCs showed luminal staining patterns. The percentage of mismatch repair deficiency (dMMR) in the non-IMPC group was much higher than that in the IMPC group (14.7% vs 4.7%). The overall survival time of patients with IMPCs was significantly less than that of patients with non-IMPCs (P = .002), then that of IMPCs-H was lower than that of IMPCs-L (P = .030). Logistic regression revealed that patients with IMPCs were associated with lymph metastasis, regardless of the proportion of IMPCs. Multivariate analysis demonstrated both IMPCs-L and IMPCs-H as negative prognostic factors. CONCLUSIONS: IMPCs are significantly associated with lymph node metastasis and poor outcome, and even a minor component (≤5%) may render significant information and should therefore be part of the pathology report.


Assuntos
Neoplasias Colorretais/secundário , Neoplasias Colorretais/cirurgia , Linfonodos/patologia , Metástase Linfática/patologia , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias/métodos , Síndromes Neoplásicas Hereditárias/epidemiologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
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