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1.
Lancet Oncol ; 21(12): 1620-1629, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33271092

RESUMO

BACKGROUND: A prospective, pooled analysis of six randomised phase 3 trials was done to investigate disease-free survival regarding non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer; non-inferiority was not shown. Here, we report the final overall survival results. METHODS: In this prospective, pooled analysis of six randomised phase 3 trials, we included patients with stage III colon cancer aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0-1 recruited between June 20, 2007, and Dec 31, 2015, across 12 countries in the CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, and HORG trials, who started any treatment (modified intention-to-treat). Patients in all trials were randomly assigned to 3 months or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks or capecitabine and oxaliplatin (CAPOX) in different doses and methods every 3 weeks, at the treating physician's discretion. The primary endpoint was disease-free survival (time to relapse, secondary colorectal primary tumour, or death due to all causes), and overall survival (time to death due to all causes) was the prespecified secondary endpoint. The non-inferiority margin for overall survival was set as a hazard ratio (HR) of 1·11. Pre-planned subgroup analyses included regimen and risk group. Non-inferiority was declared if the one-sided false discovery rate adjusted (FDRadj) p value was less than 0·025. FINDINGS: With median follow-up of 72·3 months (IQR 72·2-72·5), 2584 deaths among 12 835 patients were observed. 5064 (39·5%) patients received CAPOX and 7771 (60·5%) received FOLFOX. 5-year overall survival was 82·4% (95% CI 81·4-83·3) with 3 months of therapy and 82·8% (81·8-83·8) with 6 months of therapy (HR 1·02 [95% CI 0·95-1·11]; non-inferiority FDRadj p=0·058). For patients treated with CAPOX, 5-year overall survival was 82·1% (80·5-83·6) versus 81·2% (79·2-82·9; HR 0·96 [0·85-1·08]); non-inferiority FDRadj p=0·033), and for patients treated with FOLFOX 5-year overall survival was 82·6% (81·3-83·8) and 83·8% (82·6-85·0; HR 1·07 [0·97-1·18]; non-inferiority FDRadj p=0·34). Updated disease-free survival results confirmed previous findings (HR 1·08 [95% CI 1·02-1·15]; non-inferiority FDRadj p=0·25). Data on adverse events were not further recorded. INTERPRETATION: Non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer was not confirmed in terms of overall survival, but the absolute 0·4% difference in 5-year overall survival should be placed in clinical context. Overall survival results support the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies, and cost associated with a shorter treatment duration. FUNDING: US National Cancer Institute.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina/administração & dosagem , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
2.
Medicine (Baltimore) ; 99(46): e23024, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181667

RESUMO

Transforming growth factor-beta (TGF-ß2) is an important cytokine regulating immune cell function. However, whether TGF-ß2 controls the invasion of colorectal cancer (CRC) by immune cells is unknown. Therefore, we evaluated the expression of TGF-ß2 using multiple databases and determined the relationship between TGF-ß2 expression and tumor immune infiltration defined by a set of genetic markers. The analysis demonstrated that the expression of TGF-ß2 is closely related to the outcome of many cancers, and this correlation was particularly strong in CRC. In addition, the increased expression of TGF-ß2 was significantly associated with the expression of various markers of specific immune cell subpopulations, and overexpression of TGF-ß2 was closely related to the prognosis of colon cancer patients. Moreover, TGF-ß2 was related to the prognosis and infiltration of the tumor by immune cells in CRC patients. The obtained results indicate that TGF-ß2 is a critical factor regulating the recruitment of immune cells and controls their infiltration into colorectal tumors. Thus, high expression of TGF-ß2 not only facilitates the prognosis in CRC patients, but also may provide a new target for the treatment of CRC.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias Colorretais/mortalidade , Imunidade Celular/genética , Linfócitos/imunologia , Fator de Crescimento Transformador beta2/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Humanos , Estimativa de Kaplan-Meier , Prognóstico
3.
Nucleic Acids Res ; 48(21): 12234-12251, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33211885

RESUMO

Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment.


Assuntos
Neoplasias do Colo/tratamento farmacológico , DNA Glicosilases/genética , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Poli(ADP-Ribose) Polimerase-1/imunologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Dano ao DNA , DNA Glicosilases/antagonistas & inibidores , DNA Glicosilases/metabolismo , Reparo do DNA/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Guanina/análogos & derivados , Guanina/metabolismo , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Terapia de Alvo Molecular , Estresse Oxidativo , Poli(ADP-Ribose) Polimerase-1/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Arq Gastroenterol ; 57(2): 172-177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206858

RESUMO

BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage. OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center. METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI). RESULTS: Of 2,279 colorectal cancer cases analyzed, 58.4% were in the colon. The 5-year overall survival rate for colorectal cancer patients was 63.5% (65.6% and 60.6% for colonic and rectal malignancies, respectively). The risk of death was elevated for patients in the 50-74-year (HR=1.24, 95%CI =1.02-1.51) and ≥75-year (HR=3.02, 95%CI =2.42-3.78) age groups, for patients with rectal cancer (HR=1.37, 95%CI =1.11-1.69) and for those whose treatment was started >60 days after diagnosis (HR=1.22, 95%CI =1.04-1.43). The risk decreased for patients diagnosed in recent time periods (2005-2009 HR=0.76, 95%CI =0.63-0.91; 2010-2013 HR=0.69, 95%CI =0.57-0.83). CONCLUSION: Better survival of patients with colorectal cancer improves with early stage and started treatment within 60 days of diagnosis. Age over 70 years old was an independent factor predictive of a poor prognosis. The overall survival increased to all patients treated in the period 2000-2004 to 2010-2013.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias Colorretais/mortalidade , Neoplasias Retais/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Brasil/epidemiologia , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Sobrevida , Análise de Sobrevida , Taxa de Sobrevida
5.
Medicine (Baltimore) ; 99(40): e22447, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019430

RESUMO

The aim of this study was to investigate the relationship between textbook outcome and survival in patients with surgically treated colon cancer. A total of 804 surgical cases were enrolled between June 1, 2010 and December 31, 2014. Textbook outcome was defined as patients who had colon cancer surgery and met the six healthcare parameters of surgery within 6 weeks, radical resection, lymph node (LN) yield ≥12, no ostomy, no adverse outcome and colonoscopy before/after surgery within 6 months. The effect of textbook outcome on 5-year disease-specific survival (DSS) was calculated using the Kaplan-Meier method. A Cox regression model was used to find significant independent variables and stratified analysis used to determine whether text-book outcome had a survival benefit. A textbook outcome was achieved in 59.5% of patients undergoing colon cancer surgery. Important obstacles to achieving textbook outcome were no stomy, no adverse outcome and LN yield ≥12. Patients with text-book outcome had statistically significant better 5-year DSS compared to those with-out (80.1% vs. 58.3%). Multivariate analyses indicated that colon cancer patients with textbook outcome had better 5-year DSS after adjusting for various confounders ([aHR], 0.44; 95% CI, 0.34-0.57). Thus, besides being an index of short-term quality of care, textbook outcomes could be used as a prognosticator of long-term outcomes, such as 5-year survival rates.


Assuntos
Neoplasias do Colo/cirurgia , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Idoso , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
6.
JAMA Netw Open ; 3(10): e2020425, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33074326

RESUMO

Importance: In the pivotal Bevacizumab-Avastin Adjuvant (AVANT) trial, patients with high-risk stage II colon cancer (CC) had 5-year and 10-year overall survival (OS) rates of 88% and 75%, respectively, with adjuvant fluorouracil and oxaliplatin-based chemotherapy; however, the trial did not demonstrate a disease-free survival (DFS) benefit of adding bevacizumab to oxaliplatin-based chemotherapy in stage III CC and suggested a detrimental effect on OS. The Long-term Survival AVANT (S-AVANT) study was designed to collect extended follow-up for patients in the AVANT trial. Objective: To explore the efficacy of adjuvant bevacizumab combined with oxaliplatin-based chemotherapy in patients with high-risk, stage II CC. Design, Setting, and Participants: This prespecified secondary end point analysis of the AVANT and S-AVANT studies included 573 patients with curatively resected high-risk stage II CC and at least 1 of the following criteria: stage T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age younger than 50 years, or fewer than 12 nodes analyzed. The AVANT study was a multicenter randomized stage 3 clinical trial. Data were collected from December 2004 to February 2019, and data for this study were analyzed from March to September 2019. Intervention: Patients were randomly assigned to receive 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4), FOLFOX4 with bevacizumab, or capecitabine and oxaliplatin (XELOX) with bevacizumab. Main Outcomes and Measures: The primary end points of this secondary analysis were DFS and OS in patients with high-risk stage II CC. Results: The AVANT study included 3451 patients, of whom 573 (16.6%) had high-risk stage II CC (192 [33.5%] randomized to FOLFOX4 group; 194 [33.9%] randomized to FOLFOX4 with bevacizumab group; 187 [32.6%] randomized to XELOX with bevacizumab group). With a median (interquartile range) age of 57.0 (47.2-65.7) years, the study population comprised 325 men (56.7%) and 248 women (43.3%). After a median (interquartile range) follow-up of 6.9 (6.1-11.3) years, the 3-year DFS and 5-year OS rates were 88.2% (95% CI, 83.7%-93.0%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 group, 86.6% (95% CI, 81.8%-91.6%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 with bevacizumab group, and 86.7% (95% CI, 81.8%-91.8%) and 93.2% (95% CI, 89.6%-97.0%) in the XELOX with bevacizumab group, respectively. The DFS hazard ratio was 0.94 (95% CI, 0.59-1.48; P = .78) for FOLFOX4 with bevacizumab vs FOLFOX4 and 1.07 (95% CI, 0.69-1.67; P = .76) for XELOX with bevacizumab vs FOLFOX4. The OS hazard ratio was 0.92 (95% CI, 0.55-1.55; P = .76) for FOLFOX4 with bevacizumab vs FOLFOX4 and 0.85 (95% CI, 0.50-1.44; P = .55) for XELOX with bevacizumab vs FOLFOX4. Conclusions and Relevance: In this secondary analysis of data from the AVANT trial, adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II CC. The findings suggest that the definition of high-risk stage II CC needs to be revisited. Trial Registration: ClinicalTrial.gov Identifiers: AVANT (NCT00112918); S-AVANT (NCT02228668).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Oxaloacetatos/uso terapêutico , Idoso , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Modelos de Riscos Proporcionais , Resultado do Tratamento
7.
PLoS One ; 15(10): e0240715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064784

RESUMO

PURPOSE: This study aimed to determine the probability and prognostic factors of colon cancer-specific mortality (CCSM) and noncancer-specific mortality (NCSM) for patients with stage I/II colon cancer and evaluate the association of age on cause-specific mortality. MATERIALS AND METHODS: From Surveillance, Epidemiology, and End Results (SEER) database, we identified 33152 patients with stage I/II colon cancer undergoing surgery between 2004 and 2011. The cumulative incidence of CCSM and NCSM was calculated, and competing risk analysis was performed to investigate prognostic factors for cause-specific mortality. RESULTS: In patients <50, 50-75, and >75 years of age, 5-year cumulative incidence of CCSM was 5.7%, 7.8%, and 16.1%, respectively (overall, 10.6%); 5-year cumulative incidence of NCSM was 2.2%, 7.1%, and 26.9%, respectively (overall, 13.8%). The probability of CCSM and NCSM increased with advanced age. The 5-year cumulative incidence of CCSM was higher than NCSM in patients <50 years of age, whereas lower in patients >75 years of age. The probability of CCSM and NCSM was similar in patients 50-75 years of age. Competing-risk multivariable analysis demonstrated that increasing age was a strong predictor of CCSM (per year increase, SHR 1.03,95% confidence interval [CI]: 1.03-1.04). Age was most predictive of NCSM: (per year increase, SHR 1.08, 95% CI: 1.08-1.08). CONCLUSION: Age was significantly associated with an increased cumulative incidence of CCSM and NCSM of patients with stage I/II colon cancer underwent surgery. NCSM was a significant competing event and should be adequately considered when performing survival analysis.


Assuntos
Causas de Morte , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Fatores Etários , Idoso , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Medição de Risco
8.
Am J Surg Pathol ; 44(12): 1685-1698, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32868525

RESUMO

Grade 3 (G3, poorly differentiated) is an important treatment-decision factor in stage II colon cancer, but no unified diagnostic criteria are established. According to previous studies, an intratumoural poorly differentiated area with no glandular formation (POR) that fills the microscopic field of a ×40 objective lens was an essential factor that defined G3. We aimed to prospectively validate this in a randomized controlled study of adjuvant chemotherapy (SACURA trial). We enrolled 991 patients with stage II colon cancer. POR was graded according to the ×40 objective lens rule and the intensity of poorly differentiated clusters (Grade), and its prognostic power was compared with that of the conventional tumor grade on the basis of predominant histology rule (Grade). According to Grade, 313, 526, and 152 tumors were classified as G1, G2, and G3, respectively, and the 5-year relapse-free survival (RFS) rates were 91.1%, 82.9%, and 74.7%, respectively (P<0.0001). When G3 and G3 were alternatively added to the prognostic model consisting of 8 conventional factors, only G3 was a significant factor for RFS (P=0.040, Wald test). The adverse impact of G3 on RFS was greater in the microsatellite stable/microsatellite instability-low subset than that in the full analysis set. In the microsatellite stable/microsatellite instability-low subset, the 5-year RFS rate of patients with G3 tumors in the chemotherapy group achieved greater improvement (9.1%) than the surgery-alone group. The least differentiation policy with the ×40 objective lens rule may be highlighted as the diagnostic criterion for G3 because of its validated prognostic value.


Assuntos
Adenocarcinoma/patologia , Diferenciação Celular , Neoplasias do Colo/patologia , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Idoso , Quimioterapia Adjuvante , Colectomia , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Intervalo Livre de Doença , Feminino , Humanos , Japão , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
9.
Cancer Sci ; 111(10): 3873-3880, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32885537

RESUMO

In 1955, an outbreak of arsenic poisoning caused by the ingestion of arsenic-contaminated Morinaga Dry Milk occurred in western Japan. This study aimed to assess the mortality and cancer incidence risk among Japanese individuals who were poisoned during this time as infants. In total, 6223 survivors (mean age at enrollment, 27.5 y) who had ingested contaminated milk when they were aged ≤ 2 y participated in this study. Follow-up was conducted from 1982 to 2018 (mean follow-up duration, 30.3 y). Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare mortality and cancer incidence rates of subjects with the respective Japanese population rates, and 95% confidence intervals (95% CIs) of the SMR and SIR were also calculated. In total, 561 deaths and 524 new cancer cases were observed. A statistically significant increase in mortality rate was observed for all causes (SMR, 1.15; 1.01-1.19), nervous system disease (2.83, 1.62-4.19), respiratory disease (2.02, 1.37-2.62), genitourinary system disease (2.25, 1.10-3.73), and traffic accident (2.03, 1.14-3.04). In contrast, a significant decrease in cancer incidence rate was observed for all cancers (SIR, 0.96; 0.84-0.99), stomach cancer (0.77, 0.57-0.92), colon cancer (0.63, 0.41-0.85), rectum cancer (0.69, 0.43-0.95), and breast cancer (0.72, 0.52-0.89). Liver cancer showed a high mortality rate (SMR, 1.68; 1.06-2.31). In this study, after the long-term follow-up we revealed overall and cause-specific mortality and cancer incidence risk among survivors who ingested arsenic-contaminated dry milk as infants.


Assuntos
Intoxicação por Arsênico/mortalidade , Neoplasias Hepáticas/mortalidade , Leite/efeitos adversos , Pós/efeitos adversos , Adulto , Animais , Intoxicação por Arsênico/patologia , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/mortalidade , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/mortalidade , Feminino , Humanos , Lactente , Neoplasias Hepáticas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/induzido quimicamente , Neoplasias Retais/mortalidade , Risco , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/mortalidade , Sobreviventes
10.
Dis Colon Rectum ; 63(10): 1383-1392, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32969881

RESUMO

BACKGROUND: Prognostic and pathologic risk factors typically guide clinicians and patients in their choice of surveillance or adjuvant chemotherapy when managing high-risk stage II colon cancer. However, variations in treatment and outcomes in patients with stage II colon cancer remain. OBJECTIVE: This study aimed to assess the survival benefits of treatments concordant with suggested therapeutic options from Watson for Oncology, a clinical decision support system. DESIGN: This is a retrospective observational study of concordance between actual treatment and Watson for Oncology therapeutic options. SETTING: This study was conducted at a top-tier cancer center in China. PATIENTS: Postoperative treatment data were retrieved from the electronic health records of 306 patients with high-risk stage II colon adenocarcinoma. MAIN OUTCOME MEASURES: The primary outcomes measured were the treatment patterns plus 3- and 5-year overall and disease-free survival for concordant and nonconcordant cases. RESULTS: Overall concordance was 90%. Most nonconcordant care resulted from adjuvant chemotherapy use (rather than surveillance) in patients with high-level microsatellite instability and ≥70 years old. No difference in overall survival (p = 0.56) or disease-free survival (p = 0.19) was observed between concordance groups. Patients receiving adjuvant chemotherapy had significantly higher 5-year overall survival than those undergoing surveillance (94% vs 84%, p = 0.01). LIMITATIONS: This study was limited by the use of retrospective cases drawn from patients presenting for surgery, the lack of complete follow-up data for 58% of patients who could not be included in the analysis, and a survival analysis that assumes no unmeasured correlation between survival and censoring. CONCLUSIONS: Watson for Oncology produced therapeutic options highly concordant with human decisions at a top-tier cancer center in China. Treatment patterns suggest that Watson for Oncology may be able to guide clinicians to minimize overtreatment of patients with high-risk stage II colon cancer with chemotherapy. Survival analyses suggest the need for further investigation to specifically assess the association between surveillance, single-agent and multiagent chemotherapy, and survival outcomes in this population. See Video Abstract at http://links.lww.com/DCR/B291. APOYO A LA DECISIÓN CLÍNICA DEL CÁNCER DE COLON EN ESTADIO II DE ALTO RIESGO: UN ESTUDIO DEL MUNDO REAL SOBRE LA CONCORDANCIA DEL TRATAMIENTO Y LA SUPERVIVENCIA: Los factores de riesgo pronósticos y patológicos generalmente guían a los médicos y pacientes en su elección de vigilancia o quimioterapia adyuvante cuando se trata el cáncer de colon en estadio II de alto riesgo. Sin embargo, las variaciones en el tratamiento y los resultados en pacientes con cáncer de colon en estadio II permanecen.Evaluar los beneficios de supervivencia de los tratamientos concordantes con las opciones terapéuticas sugeridas por "Watson for Oncology" (Watson para la oncología), un sistema de apoyo a la decisión clínica.Estudio observacional retrospectivo de concordancia entre el tratamiento real y las opciones terapéuticas de Watson para oncología.Un centro oncológico de primer nivel en China.Datos de tratamiento postoperatorio de registros de salud electrónicos de 306 pacientes con adenocarcinoma de colon en estadio II de alto riesgo.Patrones de tratamiento más supervivencia global y libre de enfermedad a 3 y 5 años para casos concordantes y no concordantes.La concordancia general fue del 90%. La mayoría de la atención no concordante resultó del uso de quimioterapia adyuvante (en lugar de vigilancia) en pacientes de alto nivel con inestabilidad de microsatélites y pacientes ≥70 años. No se observaron diferencias en la supervivencia global (p = 0,56) o la supervivencia libre de enfermedad (p = 0,19) entre los grupos de concordancia. Los pacientes que recibieron quimioterapia adyuvante tuvieron una supervivencia global a los 5 años significativamente más alta que los que fueron sometidos a vigilancia (94% frente a 84%, p = 0,01).Uso de casos retrospectivos extraídos de pacientes que se presentan para cirugía, falta de datos de seguimiento completos para el 58% de los pacientes que no pudieron ser incluidos en el análisis, y análisis de supervivencia que asume que no exite una correlación no medida entre supervivencia y censura.Watson para Oncología produjo opciones terapéuticas altamente concordantes con las decisiones humanas en un centro oncológico de primer nivel en China. Los patrones de tratamiento sugieren que Watson para Oncología puede guiar a los médicos para minimizar el sobretratamiento de pacientes con cáncer de colon en estadio II de alto riesgo con quimioterapia. Los análisis de supervivencia sugieren la necesidad de realizar mas investigaciónes para evaluar específicamente la asociación entre la vigilancia, la quimioterapia con uno solo o múltiples agentes y los resultados de supervivencia en esta población. Consulte Video Resumen en http://links.lww.com/DCR/B291. (Traducción-Dr. Gonzalo Hagerman).


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Sistemas de Apoio a Decisões Clínicas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Quimioterapia Adjuvante , China , Colectomia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
11.
Dis Colon Rectum ; 63(10): 1372-1382, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32969880

RESUMO

BACKGROUND: Global experience with splenic flexure cancer is limited because of its low incidence. Both limited (segmental) and extended resections are performed, because agreement on which is the adequate procedure has not been reached. OBJECTIVE: The purpose of this study was to investigate whether segmental resection is as safe and effective as extended resection. DESIGN: This nationwide retrospective cohort study included all consecutive resections of splenic flecure cancer between January 2006 and December 2016 using data from the National Colorectal Cancer Network of the Italian Society of Surgical Oncology following the guidelines set out in the STROBE statement. SETTING: Data were obtained for 31 Italian Referral Centers for Colorectal Surgery. PATIENTS: A total of 1304 patients were submitted to resection of the splenic flexure (n = 791, 60.7%) or extended procedures (extended right and left colectomies; n = 513, 39.3%). MAIN OUTCOME MEASURES: We evaluated Clavien-Dindo ≥3 postoperative complications and oncological (number of lymph nodes removed, length of free proximal and distal margins, rate of R0 resections) and survival outcomes. RESULTS: The 2 arms were well balanced in regard to sex, BMI, ASA and Eastern Cooperative Oncology Group scores, and disease stage. Limited resection was performed more frequently using a minimally invasive approach (62.1% vs 50.9%, p < 0.001) and with shorter operation times than extended procedures (165 vs 189 minutes, p < 0.001), but the same Clavien-Dindo ≥3 postoperative complications (6.44% vs 6.43%, p = 0.99), 30-day mortality (0.63% vs 0.38%), oncological outcomes, and survival rates (5-year overall survival 0.84 vs 0.83, 5-year progression-free survival 0.85 vs 0.84). LIMITATIONS: There are limitations inherent to the retrospective nature of the study and a potential lack of consistency in treatment across centers over time. Indications as to why a specific operation was chosen were based mostly on surgeons' beliefs. CONCLUSIONS: Segmental resection is a safe and effective treatment option for cancer of the splenic flexure. See Video Abstract at http://links.lww.com/DCR/B307. LA RESECCIÓN DE COLON SEGMENTARIA ES UNA OPCIÓN DE TRATAMIENTO SEGURA Y EFICAZ PARA EL CÁNCER DE COLON DE LA FLEXIÓN ESPLÉNICA: UN ESTUDIO RETROSPECTIVO A NIVEL NACIONAL DE LA SOCIEDAD ITALIANA DE ONCOLOGÍA QUIRÚRGICA - GRUPO COLABORATIVO RED DE CÁNCER COLORRECTAL: La experiencia global con el cáncer de flexión esplénica es limitada debido a su baja incidencia. Se realizan resecciones limitadas (segmentarias) y extendidas, ya que no se ha llegado a un acuerdo sobre cuál es el procedimiento adecuado.El propósito de este estudio fue investigar si la resección segmentaria es tan segura y efectiva como la resección extendida.Este estudio de cohorte retrospectivo a nivel nacional incluyó todas las resecciones consecutivas de cáncer de flecura esplénica entre enero de 2006 y diciembre de 2016 utilizando datos de la Red Nacional de Cáncer Colorrectal de la Sociedad Italiana de Oncología Quirúrgica siguiendo las pautas establecidas en la declaración STROBE.Se obtuvieron datos para 31 centros de referencia italianos para cirugía colorrectal.Un total de 1304 pacientes fueron sometidos a resección de la flexión esplénica (n = 791, 60.7%) o procedimientos extendidos (colectomías extendidas derecha e izquierda; n = 513, 39.3%).Evaluamos Clavien-Dindo ≥3 complicaciones postoperatorias y oncológicas (número de ganglios linfáticos extirpados, longitud de márgenes proximales y distales libres, tasa de resecciones R0) y resultados de supervivencia.Los dos brazos estaban bien equilibrados en cuanto a sexo, IMC, ASA y puntajes ECOG, y etapa de la enfermedad. La resección limitada se realizó con mayor frecuencia utilizando un enfoque mínimamente invasivo (62.1% versus 50,9%, p < 0.001) y con tiempos de operación más cortos que los procedimientos extendidos (165 min versus 189 min, p <0.001), pero el mismo Clavien-Dindo ≥3 complicaciones postoperatorias (6,44% versus 6,43%, p = 0.99), mortalidad a los 30 días (0,63% versus 0,38%), resultados oncológicos y tasas de supervivencia (5-y OS 0,84 versus 0,83, 5-PFS 0,85 versus 0,84).Existen limitaciones inherentes a la naturaleza retrospectiva del estudio y una posible falta de consistencia en el tratamiento entre centros a lo largo del tiempo. Las indicaciones de por qué se eligió una operación específica se basaron principalmente en crieterios de los cirujanos.La resección segmentaria es una opción de tratamiento segura y efectiva para el cáncer de la flexión esplénica. Consulte Video Resumen en http://links.lww.com/DCR/B307. (Traducción-Dr. Adrian Ortega).


Assuntos
Colectomia/métodos , Colo Transverso/cirurgia , Neoplasias do Colo/cirurgia , Idoso , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Humanos , Itália , Excisão de Linfonodo , Masculino , Margens de Excisão , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Estudos Retrospectivos , Taxa de Sobrevida
12.
Dis Colon Rectum ; 63(10): 1455-1465, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32969889

RESUMO

BACKGROUND: An oxaliplatin-based chemotherapy regimen improves the survival outcomes of patients with stage III colon cancer. However, its complications are well-known. OBJECTIVE: The purpose of this study was to distinguish between the survival outcomes of patients who underwent curative resection for stage III colon cancer with oxaliplatin chemotherapy and those who underwent such resection without oxaliplatin chemotherapy. DESIGN: This was a retrospective analytical study based on prospectively collected data. SETTINGS: This study used data on patients who underwent surgery at our hospital between January 2010 and December 2014. PATIENTS: A cohort of 254 consecutive patients who underwent curative resection for stage III colon cancer was included in this study. The patients were divided into 2 groups: patients with isolated pericolic lymph node metastasis (n = 175) and those with extrapericolic lymph node metastasis (n = 79). MAIN OUTCOME MEASURES: Clinicopathologic features and 3-year survival outcomes were analyzed with and without oxaliplatin therapy in the pericolic lymph node group. RESULTS: The pericolic lymph node group showed significantly improved overall survival compared with the extrapericolic lymph node group at a median follow-up of 48.5 months (95.8% vs 77.8%; p < 0.001). In contrast, there was no significant difference in overall survival (99.0% vs 92.0%; p = 0.137) and disease-free survival (89.1% vs 88.2%; p = 0.460) between the oxaliplatin and nonoxaliplatin subgroups of the pericolic lymph node group. Multivariate analysis showed that the administration of oxaliplatin chemotherapy to the pericolic lymph node group did not lead to a significant difference in the overall survival (p = 0.594). LIMITATIONS: The study was limited by its retrospective design and single institutional data analysis. CONCLUSIONS: This study suggests that the anatomic extent of metastatic lymph nodes could affect patient prognosis, and the effect of oxaliplatin-based adjuvant chemotherapy may not be prominent in stage III colon cancer with isolated pericolic lymph node metastasis.


Assuntos
Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Metástase Linfática/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Fluoruracila , Humanos , Leucovorina , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos , Oxaloacetatos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
14.
Int J Clin Oncol ; 25(12): 2075-2082, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32785799

RESUMO

BACKGROUND: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan. METHODS: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy. RESULTS: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13). CONCLUSION: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Oxaliplatina/efeitos adversos , Esplenopatias/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Japão , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem , Prognóstico , Esplenopatias/diagnóstico por imagem
15.
Surgery ; 168(5): 786-792, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32771298

RESUMO

BACKGROUND: Bladder invasion by colon cancer is rare; however, its management is still controversial. Our objective was to report outcomes and identify risk factors for local recurrence in colon cancer with clinically suspected bladder invasion. METHODS: We conducted a retrospective study in 23 centers in France. All patients who underwent colon surgery with bladder resection (2010-2017) were included. Metastatic and recurrent colon cancers were excluded. RESULTS: One hundred and seventeen patients (men = 73) were included. Partial cystectomy occurred in 108 patients (92.3%), with a total cystectomy occurring in 9 patients (7.7%). Neoadjuvant treatment was given to 31 patients (26.5%). Major morbidity was 20.5%. R0 resection rates were 87.2%. Histologically confirmed bladder invasion was present in 47%. Thirty-four patients were pN+, while 60 patients (51.3%) received adjuvant chemotherapy. Mean follow-up was 33.8 months. Three-year overall survival and disease-free survival were 82.9% and 59.5%. Rates of local recurrence and distant recurrence were 14.5% and 18.8%, respectively; the local recurrences (11/17; 65%) were in the bladder, while 4 of these patients had a bladder recurrence despite not having histologically confirmed bladder invasion at the index surgery. The rate of bladder recurrence after histologic bladder invasion was 13% (7/55), while the rate of bladder recurrence without primary bladder invasion was 7% (4/62) (P = .343). Neoadjuvant therapy, type of cystectomy, and adjuvant therapy did not influence local recurrence (P > .445 each). R1 bladder resections, when compared with a R0 bladder resections, were associated with an increased rate of local recurrence (63% vs 10%; P < .0001). CONCLUSION: Clinically suspected bladder invasion increases local recurrence even in the absence of histologically confirmed bladder invasion. Only complete resections with R0 margins decrease local recurrence. Careful, detailed postoperative surveillance is required, even without pathologic bladder invasion.


Assuntos
Neoplasias do Colo/patologia , Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia
16.
Ann Surg ; 272(5): 738-743, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833768

RESUMO

OBJECTIVE: The purpose of this population-based study was to compare decompressing stoma (DS) as bridge to surgery (BTS) with emergency resection (ER) for left-sided obstructive colon cancer (LSOCC) using propensity-score matching. SUMMARY BACKGROUND DATA: Recently, an increased use of DS as BTS for LSOCC has been observed in the Netherlands. Unfortunately, good quality comparative analyses with ER are scarce. METHODS: Patients diagnosed with nonlocally advanced LSOCC between 2009 and 2016 in 75 Dutch hospitals, who underwent DS or ER in the curative setting, were propensity-score matched in a 1:2 ratio. The primary outcome measure was 90-day mortality, and main secondary outcomes were 3-year overall survival and permanent stoma rate. RESULTS: Of 2048 eligible patients, 236 patients who underwent DS were matched with 472 patients undergoing ER. After DS, more laparoscopic resections were performed (56.8% vs 9.2%, P < 0.001) and more primary anastomoses were constructed (88.5% vs 40.7%, P < 0.001). DS resulted in significantly lower 90-day mortality compared to ER (1.7% vs 7.2%, P = 0.006), and this effect could be mainly attributed to the subgroup of patients over 70 years (3.5% vs 13.7%, P = 0.027). Patients treated with DS as BTS had better 3-year overall survival (79.4% vs 73.3%, hazard ratio 0.36, 95% confidence interval 0.20-0.65) and fewer permanent stomas (23.4% vs 42.4%, P < 0.001). CONCLUSIONS: In this nationwide propensity-score matched study, DS as a BTS for LSOCC was associated with lower 90-day mortality and better 3-year overall survival compared to ER, especially in patients over 70 years of age.


Assuntos
Neoplasias do Colo/cirurgia , Colostomia , Obstrução Intestinal/cirurgia , Idoso , Neoplasias do Colo/mortalidade , Descompressão Cirúrgica , Procedimentos Cirúrgicos Eletivos , Emergências , Feminino , Humanos , Obstrução Intestinal/mortalidade , Masculino , Países Baixos , Complicações Pós-Operatórias/mortalidade , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
17.
Cancer Invest ; 38(7): 406-414, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32762373

RESUMO

BACKGROUND: Programmed death 1 (PD-1) and its ligand PD-L1 play a key dysfunction of T lymphocytes. The purpose of this study was to assess and compare the prognostic role of tumor- TILs and its relationship with PD-L1 expression in stage II and III colon cancer. METHODS: Immunohistochemisty was used to assess the densities of CD8+, CD4+, and FOXP3+ cells, and PD-L1 expression in intraepithelial tumor site from 58 stage II and III colon cancers. These were evaluated for association with histopathologic features and overall survival. RESULTS: PD-L1-positive tumors contained a higher number of CD8+ TILs with statistical significance (p = 0.001). CD4+ TILs showed positive correlation with PD-L1 expression (p = 0.034). There were no associations between PD-L1 expression and FOXP3+ TILs. Microsatellite instability (MSI)-high status (p = 0.001; Odd ration 18.0; 95% CI = 4.3-74.8) was the strongest prognostic factor along with mucinous/poor cell differentiation, CD8 and right tumor location was associated with PD-L1 expression (p = 0.024, 0.035 and 0.033, respectively). CONCLUSION: This study demonstrated that PD-L1 expression was associated with MSI-high, increased CD8+ TILs, mucinous and poor cell differentiation, and right-sided tumor location.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Sobrevida
18.
Am J Surg ; 220(6): 1605-1612, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32680623

RESUMO

AIM: Surgery with or without chemotherapy represent the only curative option for patients with colon cancer. However, some patients refuse treatment despite the recommendation. This study aims to identify the incidence, risk factors and impact on survival associated with refusal. METHODS: A National Cancer Data Base (NCDB) analysis between 1998 and 2012 was performed. We identified 924,290 patients with potentially treatable colon cancer. Patients who underwent treatment were compared with patients that refused. RESULTS: 7152 patients refused surgery. On multivariable analysis, patients were more likely to refuse if they were older (OR = 1.14; 95% CI 1.14-1.15), female (OR = 1.20; 95% CI 1.12-1.28), African American (vs White, OR = 2.30; 95% CI 2.10-2.51) or on Medicaid (vs private, OR = 3.06; 95% CI 2.49-43.77). Overall survival was worse in patients that refused surgery [median survival 6.8 vs 24 months, Cox hazard ratio (HR) 3.41; 95%CI 3.12-3.60]. Furthermore, 11,334 patients with path. stage III disease refused adjuvant chemotherapy. CONCLUSIONS: Refusal of treatment affects survival and is independently associated with several variables (gender, race, insurance status), therefore raising the concern that socioeconomic factors may drive decisions.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
19.
Sci Rep ; 10(1): 11951, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686693

RESUMO

Transcobalamin (TCN1) is a vitamin B12 (cobalamin)-binding protein that regulates cobalamin homeostasis. Recent studies and bioinformatic analyses have found that TCN1 is highly expressed in cancer tissues and is associated with tumour aggressiveness and poor prognosis. The present study aimed to detect TCN1 as a novel biomarker for prognosis and chemosensitivity of colon cancer. Next-generation sequencing showed that TCN1 was one of several upregulated mRNAs in colon cancer, which was verified by further bioinformatics analyses. Western blotting (n = 9) and quantitative real time polymerase chain reaction (qRT-PCR, n = 30) revealed that TCN1 was highly expressed in colon cancer tissues at both the protein and mRNA level. A total of 194 cases of colon cancer were examined by immunohistochemistry and revealed that TCN1 expression level was related to advanced stages (P < 0.005). Kaplan-Meier analysis verified that patients with lower TCN1 expression usually had longer overall survival (P = 0.008). In addition, TCN1 was highly expressed in pulmonary metastatic tumour tissues (n = 37, P = 0.025) and exhibited higher levels in right-sided colon cancer than in left-sided colon cancer (P = 0.029). TCN1 expression in specimens that had received neoadjuvant chemotherapy decreased compared with that in colonoscopy biopsy tissues (n = 42, P = 0.009). Further bioinformatics analyses verified that apoptosis pathways might have a role in high TCN1 expression. All the studies revealed that TCN1 expression in colon cancer was significantly associated with malignant biological behaviour. Therefore, TCN1 could be used as a novel biomarker for colon cancer aggressiveness and prognosis and might also be a potential biomarker for predicting neoadjuvant chemosensitivity.


Assuntos
Biomarcadores Tumorais , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica , Transcobalaminas/genética , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Transcobalaminas/metabolismo
20.
Mayo Clin Proc ; 95(11): 2429-2441, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32713607

RESUMO

OBJECTIVE: To inform potential guideline development, we investigated nonlinear associations between television viewing time (TV time) and adverse health outcomes. METHODS: From 2006 to 2010, 490,966 UK Biobank participants, aged 37 to 73 years, were recruited. They were followed from 2006 to 2018. Nonlinear associations between self-reported TV time (hours per day) and outcomes explored using penalized cubic splines in Cox proportional hazards adjusted for demographics and lifestyle. Population-attributable and potential impact fractions were calculated to contextualize population-level health outcomes associated with different TV time levels. Nonlinear isotemporal substitution analyses were used to investigate substituting TV time with alternative activities. Primary outcomes were mortality: all-cause, cardiovascular disease (CVD) and cancer; incidence: CVD and cancer; secondary outcomes were incident myocardial infarction, stroke, and heart failure and colon, lung, breast, and prostate cancer. RESULTS: Those with noncommunicable disease (109,867 [22.4%]), CVD (32,243 [6.6%]), and cancer (37,81 [7.7%]) at baseline were excluded from all-cause mortality, CVD, and cancer analyses, respectively. After 7.0 years (mortality) and 6.2 years (disease incidence) mean follow-up, there were 10,306 (2.7%) deaths, 24,388 (5.3%) CVD events, and 39,121 (8.7%) cancer events. Associations between TV time and all-cause and CVD mortality were curvilinear (Pnon-linear ≤.003), with lowest risk observed <2 hours per day. Theoretically, 8.64% (95% confidence interval [CI], 6.60-10.73) of CVD mortality is attributable to TV time. Limiting TV time to 2 hours per day might have prevented, or at least delayed, 7.97% (95% CI, 5.54-10.70) of CVD deaths. Substituting TV time with sleeping, walking, or moderate or vigorous physical activity was associated with reduced risk for all outcomes when baseline levels of substitute activities were low. CONCLUSION: TV time is associated with numerous adverse health outcomes. Future guidelines could suggest limiting TV time to less than 2 hours per day to reduce most of the associated adverse health events.


Assuntos
Nível de Saúde , Tempo de Tela , Televisão , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/etiologia , Neoplasias do Colo/mortalidade , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Neoplasias da Próstata/mortalidade , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Televisão/estatística & dados numéricos , Reino Unido/epidemiologia
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