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1.
Medicine (Baltimore) ; 99(33): e21546, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872001

RESUMO

INTRODUCTION: The efficacy of different timings of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites caused by peritoneal carcinomatosis of colorectal cancer (CRC) is not well defined. The study aims to investigate the clinical efficacy and safety of different timings of CRS with HIPEC for malignant ascites caused by peritoneal carcinomatosis from CRC. MATERIALS AND METHODS: This was a preliminary randomized controlled study performed at the Intracelom Hyperthermic Perfusion Therapy Center of the Cancer Hospital of Guangzhou Medical University (China) from December 2008 to December 2016. The patients were randomized to: CRS, followed by HIPEC (CRS+HIPEC; n = 14), and ultrasound-guided HIPEC, followed by CRS 1 to 2 weeks later (HIPEC+ delayed cytoreductive surgery (dCRS) group, n = 14). The endpoints were complete remission rate of ascites, successful complete CRS rate, and overall survival. RESULTS: Malignant ascites in all patients showed complete remission; the total effective rate was 100%. Complete CRS was not feasible in any patient. The median follow-up of the 2 groups was 41.9 and 42.3 months in the CRS+HIPEC and HIPEC+dCRS groups, respectively. Overall survival was 14.5 (95%CI: 7-19 months) and 14.3 months (95%CI: 4-21 months) (P > .05). The adverse effects of HIPEC were manageable. CONCLUSIONS: CRS+HIPEC and HIPEC+dCRS have the same efficacy in controlling malignant ascites caused by CRC and peritoneal carcinomatosis. The timing of CRS and HIPEC does not prolong the survival of patients with peritoneal carcinomatosis from CRC, even when a complete CRS is not feasible.


Assuntos
Ascite/etiologia , Ascite/terapia , Neoplasias Colorretais/complicações , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Adulto , Idoso , Ascite/mortalidade , China , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Ultrassonografia de Intervenção
2.
Medicine (Baltimore) ; 99(39): e22407, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991469

RESUMO

Colorectal cancer (CRC) is the third most common cancer in the world and is the second leading cause of cancer-related deaths. Several mutations are involved in the development of CRC. The prognostic significance of the KRAS mutation has been discussed in many studies. We aimed to investigate the prognostic significance of the number of KRAS mutations in metastatic CRC (mCRC).Patients with mutations in the KRAS gene were included in the study. They were divided into 2 groups as single mutation and multiple mutations in the KRAS gene.For the study, 425 CRC patients were screened. KRAS mutation was positive in 191 patients (45%). One hundred ninety-one patients were included in the study, 171 patients (90%) had single mutations and 20 patients (10%) had multiple mutations. Median progression-free survival was 12.8 months in patients with multiple mutations, while it was 8.8 months in patients with single mutations (P: .05). The median overall survival of patients with multiple mutations was 40.7 months, while it was 22.7 months for patients with single mutations (P = .01)We found that the presence of multiple mutations in KRAS mutant patients was associated with better overall survival and progression-free survival than a single mutation.


Assuntos
Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Turquia/epidemiologia , Adulto Jovem
3.
Medicine (Baltimore) ; 99(36): e21688, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899000

RESUMO

In this study, the National Health Insurance Research Database of Taiwan was used to examine the recurrence and death risk for stage 0 colorectal cancer patients. We examined stage 0 colorectal cancer patients to identify factors causing recurrence and death.This is a retrospective study, and stage 0 colorectal cancer patients that are registered in the Taiwan Cancer Registry of the Health Promotion Administration in 2007 to 2012 were included. The database was linked to the National Health Insurance Research Database, and subjects were followed up until the end of 2016. The mean follow-up period was 69 months. Bivariate analysis methods (log-rank test) and Cox proportional hazards model were used to evaluate the risk of recurrence and death and demographic characteristics, economic factors, environmental factors, health factors, treatment and hospitals, and absence/presence of postoperative tests were used to examine related risk factors.Our study showed that the 5-year recurrence rate and 5-year mortality rate for stage 0 colorectal cancer are 1.68% and 0.6%, respectively. For stage 0 colorectal cancer, age (61-74 years) is the only factor affecting recurrence in patients (hazard ratio (HR) = 2.44; 95% CI: 1.41-4.22), while age >75 years (HR = 4.35; 95% CI: 1.14-16.68) and Charlson Comorbidity Index >4 points (HR = 7.20, 95% CI: 2.60-19.94) can increase the risk of death. In contrast, patients who underwent one (HR = 0.27, 95% CI: 0.10-0.71) and two or more colonoscopies (HR = 0.26, 95% CI: 0.10-0.70) within 2 years after surgery can reduce the risk of death from stage 0 colorectal cancer. In addition, the risk of recurrence is higher in patients who underwent colonoscopic polypectomy (HR = 2.07, 95% CI: 0.98-4.33) and patients with rectal cancer (HR = 2.74, 95% CI: 0.96-7.83), but these differences are not statistically significant (P > .05).From this study, we can see that age and comorbidity index increase the risk of recurrence and death for stage 0 colorectal cancer, while postoperative colonoscopy can decrease the risk of death.


Assuntos
Neoplasias Colorretais/mortalidade , Recidiva Local de Neoplasia/mortalidade , Fatores Etários , Idoso , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/cirurgia , Bases de Dados Factuais , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
4.
N Z Med J ; 133(1520): 15-26, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994590

RESUMO

AIMS: To explore variations in the use of and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand. METHODS: This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016. The first chemotherapy regime was identified from Pharmaceutical Collection dataset. Logistic regression model was used to estimate the adjusted odds ratio of having chemotherapy by subgroup after adjustment for other factors. RESULTS: 27.8% (6,737/24,217) of colon cancer patients and 43.8% (3,582/8,170) of rectal cancer patients received publicly funded chemotherapy. The uptake and timeliness of chemotherapy has been improving over time. Pacific people were the least likely to receive chemotherapy, followed by Maori and Asian. Younger patients, New Zealand European, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy in less than 10 weeks post-diagnosis. Over half of the advanced colorectal cancer patients who did not receive chemotherapy were aged 80+ years or had a short life expectancy. CONCLUSIONS: Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Maori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Tratamento Farmacológico/métodos , Disparidades em Assistência à Saúde/etnologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Tratamento Farmacológico/economia , Grupos Étnicos , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Expectativa de Vida/etnologia , Expectativa de Vida/tendências , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Nova Zelândia/etnologia , Fatores de Tempo
5.
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
6.
J Environ Pathol Toxicol Oncol ; 39(2): 101-111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749120

RESUMO

Long noncoding RNAs (lncRNAs) have been reported to be involved in cancer initiation and evolution, including colorectal cancer (CRC). Nuclear-enriched abundant transcript 1 (NEAT1) exerts important functions in multiple cancers; however, the specific modulatory mechanism in CRC demands in-depth exploration. The expression levels of NEAT1, microRNA-195-5p (miR-195-5p), and centrosomal protein 55 (CEP55) were examined using quantitative real-time polymerase chain reaction (qRT-PCR), and protein expression of CEP55 was detected by Western blot assay. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazole-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Transwell migration and invasion assays were applied to evaluate cell metastasis ability. Dual-luciferase reporter assay was used to analyze the correlation among NEAT1, miR-195-5p and CEP55. The expression of NEAT1 was up-regulated in CRC tissues and cells, and overall survival was lower with high expression of NEAT1. Knockdown of NEAT1 repressed cell proliferation, migration, and invasion, while inducing apoptosis in CRC cells. NEAT1 targeted miR-195-5p and inhibited the expression of miR-195-5p. Silence of NEAT1 inhibited CRC cell proliferation, migration, and invasion, and promoted apoptosis by up-regulating miR-195-5p. MiR-195-5p targeted and suppressed CEP55 expression, and CEP55 reverted the effects induced by miR-195-5p. NEAT1 regulated the expression of CEP55 through miR-195-5p. NEAT1 promotes colorectal cancer cellular processes by regulating CEP55 expression via the sponging of miR-195-5p. Therefore, NEAT1 might play a crucial role in CRC treatments.


Assuntos
Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , Apoptose/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Mucosa Gástrica/citologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo
7.
Medicine (Baltimore) ; 99(30): e21368, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791745

RESUMO

Pulmonary metastasectomy is considered to be a feasible method for selected colorectal cancer (CRC) patients. This study aimed to optimize the individualized surgical strategy of pulmonary metastasectomy, especially in choice of surgery extent and systematic mediastinal lymph nodes dissection.Data of 267 CRC patients who underwent pulmonary metastasectomy from July 2011 to July 2017 in Shanghai Cancer Center Fudan University were reviewed. Recurrence-free survival (RFS), overall survival (OS) and other clinical characteristics were compared between patients who accepted different surgical strategy.A total of 93 (34.8%) patients underwent lobectomy, 162 (60.7%) wedge resection, and 12 (4.5%) segmentectomy. Mediastinal lymph nodes dissection or sampling was performed in 106 (39.7%) patients. The median follow-up phase was 32.5 months (range 7.2-104.7 months). Patients were divided into 2 groups according to the surgical extent, lobectomy group and sublobar resection group. The median RFS and OS were 46.4 and 76.5 months for patients underwent, respectively. In the patients whose tumor diameter was ≥ 1.5 cm, RFS (5-year; 44.9% vs 29.8%, log-rank P = .03; hazard ratio, 0.71; 95% CI 0.52-0.89, P = .026) was better in the lobectomy group; however, no difference was found in OS. Meanwhile, in the patients whose tumor size was <1.5 cm, no difference was observed in RFS, as well as in OS. In the patients with metastatic lesion size ≥1.5 cm, a trend towards better RFS was found in patients received lymph nodes dissection, but it did not reach statistical significance.Lobectomy has more curative significance for CRC patients with single pulmonary metastatic lesion ≥1.5 cm. Systematic mediastinal lymph nodes dissection did not improve clinical outcome for CRC patients occurred pulmonary metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Pneumonectomia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
PLoS One ; 15(8): e0238473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857807

RESUMO

BACKGROUND: Valid indicators are required to measure surgical quality. These ideally should be sensitive and selective while being easy to understand and adjust. We propose here the MTL30 quality indicator which takes into account 30-day mortality, transfer within 30 days, and a length of stay of 30 days as composite markers of an uneventful operative/postoperative course. METHODS: Patients documented in the StuDoQ|Colon and StuDoQ|Rectal carcinoma register of the German Society for General and Visceral Surgery (DGAV) were analyzed with regard to the effects of patient and tumor-related risk factors as well as postoperative complications on the MTL30. RESULTS: In univariate analysis, the MTL30 correlated significantly with patient and tumor-related risk factors such as ASA score (p<0.001), age (p<0.001), or UICC stage (p<0.001). There was a high sensitivity for the postoperative occurrence of complications such as re-operations (p<0.001) or subsequent bleeding (p<0.001), as well as a significant correlation with the CDC classification (p<0.001). In multivariate analysis, patient-related risk factors and postoperative complications significantly increased the odds ratio for a positive MTL30. A negative MTL30 showed a high specify for an uneventful operative and postoperative course. CONCLUSION: The MTL30 is a valid indicator of colorectal surgical quality.


Assuntos
Cirurgia Colorretal , Indicadores de Qualidade em Assistência à Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Transferência de Pacientes , Complicações Pós-Operatórias , Estudos Prospectivos , Sistema de Registros , Reoperação , Fatores de Risco , Fatores de Tempo , Adulto Jovem
9.
PLoS One ; 15(8): e0236799, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756574

RESUMO

INTRODUCTION: Numerous prior studies, even from countries with free access to care, have associated long travel time to care with poor survival in patients with colorectal cancer. METHODS: This is a data-linkage study of all 3718 patients with colorectal cancer, diagnosed between 2007 and 2013 in Northern Sweden, one of the most sparsely populated areas in Europe. Travel time to nearest hospital was calculated based on GPS coordinates and multivariable Cox regression was used to analyse possible associations between travel time and cause-specific survival. RESULTS: No association between travel time and survival was observed, either in univariable analysis (colon HR 1.00 [95% CI 0.998-1.003]; rectal HR 0.998; [95% CI 0.995-1.002]) or in multivariable Cox regression analysis (colon HR 0.999 [95% CI 0.997-1.002]; rectal HR 0.997 [95% CI 0.992-1.002]). CONCLUSIONS: In contrast to most other studies, no association between travel time and colorectal cancer survival was found; despite that longer travel time was associated with known risk factors for poorer outcome. In the Swedish health care setting, travel time does not appear to represent a barrier to care or to negatively influence outcomes.


Assuntos
Neoplasias Colorretais/mortalidade , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Escolaridade , Feminino , Humanos , Armazenamento e Recuperação da Informação , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Fatores de Tempo
10.
APMIS ; 128(10): 543-551, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32794608

RESUMO

The Hippo pathway is a tumor suppressive pathway regulating Yes-associated protein-TEA domain-containing sequence-specific transcription factor (YAP-TEAD) complex. VGLL (Vestigial-like) proteins are transcriptional cofactors competing with YAP for TEAD binding and interfering oncogenic activity of YAP-TEAD complex. We evaluated the expression of VGLL4, YAP, and TEAD4 and assessed their correlations with clinicopathologic factors and prognostic effects in 295 colorectal cancers. VGLL4 was positive in 164 (55.6%) cases and correlated with small tumor size, low pT classification, and absence of lymph node metastasis. YAP and TEAD4 were highly expressed in 138 (46.8%) cases and 144 (48.8%) cases, respectively, and high expressions were associated with presence of lymphovascular invasion and lymph node metastasis, or distant metastasis. VGLL4 expression was significantly correlated with low YAP expression (p < 0.001) and had significantly better overall survival than negative expression (p < 0.001). High YAP (HR, 2.108; 95% confidence interval, 1.239-3.584; p = 0.006) and TEAD4 (1.724; 1.021-2.912; p = 0.042) expressions were associated with poor overall survivals. The combined VGLL4pos YAPlow expression showed the best overall survival than other groups (p < 0.001). VGLL4 expression (0.381; 0.212-0.683; p = 0.001) and combined VGLL4pos YAPlow expression (0.227; 0.108-0.475; p < 0.001) were independent good prognostic factors in colorectal cancers. The expressions of VGLL4, YAP, and TEAD4 can be used as prognostic markers in colorectal cancer patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Fatores de Transcrição/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Proteínas de Ligação a DNA/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/biossíntese , Prognóstico , Análise de Sobrevida
11.
Yonsei Med J ; 61(7): 572-578, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32608200

RESUMO

PURPOSE: Wnt and mammalian target of rapamycin (mTOR) are major molecular signaling pathways associated with the development and progression of tumor, as well as the maintenance and proliferation of cancer stem cells (CSCs), in colorectal cancer (CRC). Identifying patients at risk of poor prognosis is important to determining whether to add adjuvant treatment in stage II CRC and thus improve survival. In the present study, we evaluated the prognostic value of Wnt, mTOR, and CSC markers as survival predictors in stage II CRC. MATERIALS AND METHODS: We identified 148 cases of stage II CRC and acquired their tumor tissue. Tissue microarrays for immunohistochemical staining were constructed, and the expressions of CD166, CD44, EphB2, ß-catenin, pS6 were evaluated using immunohistochemical staining. RESULTS: The expressions of CD166 (p=0.045) and pS6 (p=0.045) and co-expression of pS6/CD166 (p=0.005), pS6/CD44 (p=0.042), and pS6/CD44/CD166 (p=0.013) were negatively correlated with cancer-specific survival. Cox proportional hazard analysis showed the combination of CD166/pS6 [hazard ratio, 9.42; 95% confidence interval, 2.36-37.59; p=0.002] to be the most significant predictor related with decreased cancer-specific survival. In addition, co-expression of CD44/CD166 (p=0.017), CD166/ß-catenin (p=0.036), CD44/ß-catenin (p=0.001), and CD44/CD166/ß-catenin (p=0.001) were significant factors associated with liver metastasis. CONCLUSION: Specific combinations of CSC markers and ß-catenin/mTOR signaling could be a significant predictor of poor survival in stage II CRC.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/análise , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Serina-Treonina Quinases TOR/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Receptores de Hialuronatos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/transplante , Prognóstico , Transdução de Sinais , Serina-Treonina Quinases TOR/análise , beta Catenina
12.
Am Surg ; 86(5): 499-507, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32684032

RESUMO

OBJECTIVE: We aimed to explore the prognostic value of primary tumor and specific metastases excision on survival among patients with stage IV colorectal cancer (CRC) in the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients with stage IV CRC were selected using SEER database between 2010 and 2013. Survival rate was calculated according to the Kaplan-Meier method, and differences between curves were tested by the log-rank test. Cox proportional hazards model was used in the multivariable analysis. RESULTS: Included in this study were 27 878 patients with distant metastatic CRC. Among the single organ site of metastatic CRC, patients with solitary metastasis of lung showed the highest median overall survival (OS). Both primary and metastatic sites surgical resection for patients with liver, lung, and simultaneous liver and lung metastases had better median OS. Age younger than 65 years, Asian and Pacific Islander, distal colon and rectum, and palliative primary tumor and metastatic lesions resection were associated with better OS after multivariate analysis. Palliative primary tumor and metastatic lesions resection had a significant survival benefit compared with nonsurgical group in selected patients. CONCLUSION: These findings support the use of preemptive surgery in the management of highly selected metastatic CRC patients.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Metastasectomia , Idoso , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida
13.
S Afr Med J ; 110(5): 382-388, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32657722

RESUMO

BACKGROUND: The Colorectal Cancer South Africa (CRCSA) study is an observational cohort of patients with colorectal cancer (CRC) in Johannesburg, South Africa (SA). We found that the mean age at the time of CRC diagnosis was 56.6 years, consistent with studies from SA and sub-Saharan Africa. In high-income settings, comorbidity adversely affects CRC survival, and patients are substantially older at the time of CRC diagnosis. Given the younger age at CRC diagnosis in the CRCSA cohort, we hypothesised that comorbidity may be less prevalent and have little impact on CRC survival. OBJECTIVES: To determine the prevalence of comorbidity and whether comorbidity adversely affects overall survival (OS) of CRC patients. METHODS: Patients enrolled in the CRCSA study between January 2016 and July 2018 were included. The cohort comprised a convenience sample of adults with histologically confirmed CRC, treated at the University of the Witwatersrand Academic Teaching Hospital Complex. Demographic, clinical and histological variables were collected at baseline and participants were followed up for OS. The Charlson comorbidity index (CCI) scoring system was used to classify participants as 'no comorbidity' (CCI score 0) and '1 or more comorbidities' (CCI score ≥1). A descriptive analysis of the cohort was undertaken, while survival across comorbidity groups was compared by the Kaplan-Meier method and Cox proportional hazards (PH) regression models. Multivariable Cox PH regression was performed to examine the effect of comorbidity on survival (unadjusted) and then adjusted for variables. RESULTS: There were 424 participants, and the mean (standard deviation) age was 56.6 (14.1) years (range 18 - 91). Only 19.1% of participants had ≥1 comorbidities, of which diabetes mellitus was most frequent (12.3%), followed by chronic obstructive pulmonary disease (4.7%) and cardiovascular disease (3.1%). There was no significant difference in unadjusted and adjusted risk of death for the group with ≥1 comorbidities compared with those with no comorbidity. However, an incidental finding showed a significantly increased risk of death for those receiving potentially curative treatment later than 40 days after CRC diagnosis. CONCLUSIONS: In the CRCSA cohort from Johannesburg, comorbidity is uncommon, with no significant adverse effect on OS. If potentially curative treatment is initiated within 40 days of CRC diagnosis, OS could be improved. To fully understand the epidemiology of CRC in SA, population-based registries are essential, and future research should aim to identify health system failures that lead to delays in intervention beyond 40 days in patients with CRC.


Assuntos
Neoplasias Colorretais/mortalidade , Comorbidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Colorretais/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Amostragem , África do Sul/epidemiologia , Adulto Jovem
14.
Anticancer Res ; 40(7): 4157-4163, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620665

RESUMO

BACKGROUND/AIM: The efficacy of trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) plus bevacizumab as later-line treatment for metastatic colorectal cancer (mCRC) has been demonstrated. However, little is known about the impact of a usage history of bevacizumab in front-line treatment on the clinical benefit of combining bevacizumab with FTD/TPI. PATIENTS AND METHODS: A total of 62 patients with mCRC treated with FTD/TPI±bevacizumab was enrolled and assessed for chemotherapeutic efficacy and adverse events. RESULTS: Regardless of the usage history of bevacizumab in front-line treatment, the FTD/TPI plus bevacizumab group had a significantly better progression-free survival rate than the FTD/TPI monotherapy group, and no significant differences in the safety profile were observed between the two groups. CONCLUSION: Combining bevacizumab with FTD/TPI improves the survival outcomes with manageable toxicity, regardless of the usage history of bevacizumab in front-line treatment, in patients with mCRC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Pirrolidinas/uso terapêutico , Timidina Fosforilase/antagonistas & inibidores , Trifluridina/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Uracila/uso terapêutico , Adulto Jovem
15.
Anticancer Res ; 40(7): 4165-4171, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620666

RESUMO

BACKGROUND/AIM: The Geriatric Nutritional Risk Index (GNRI) is a prognostic indicator for several cancers; however, the association between the GNRI and colorectal liver metastasis (CRLM) remains unknown. PATIENTS AND METHODS: Eighty patients who underwent hepatectomy for synchronous CRLM were divided into two groups based on the GNRI. RESULTS: The preoperative CA19-9 levels were significantly higher in the low (GNRI ≤98; n=30) than the normal GNRI group (GNRI >98; n=50). Patients in the low GNRI group had poorer outcomes than those in the normal GNRI group. A low GNRI was an independent prognostic factor for recurrence-free survival and overall survival. Among 50 patients who experienced recurrence, only 16 of 22 patients (72.7%) in the low GNRI group could receive intensive treatment and 27 of 28 patients (96.4%) in the normal GNRI group. CONCLUSION: The GNRI is a simplified prognostic factor for patients with CRLM.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Estado Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Avaliação Geriátrica , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
16.
Medicine (Baltimore) ; 99(28): e21224, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664176

RESUMO

A great many circular RNAs (circRNAs) exist in different types of mammalian cells. Previous studies have verified that a low level of hsa_circ_0002320 is present in gastric cancer and that it might represent a good prognostic indicator. However, its value in colorectal cancer (CRC) is unclear. The aim of this research was to explore the value of hsa_circ_0002320 as a potential diagnostic biomarker for CRC prognosis.Plasma samples, CRC tissues, and adjacent normal tissues were obtained from 50 patients with CRC, before any treatment, and 100 plasma samples were acquired from healthy individuals. Hsa_circ_0002320 levels in these samples were analyzed by reverse transcription-quantitative polymerase chain reaction. Correlations between hsa_circ_0002320, clinicopathological characteristics, and overall survival (OS) of CRC patients were also investigated. Receiver-operating characteristic (ROC) curve analysis was used to assess the value of hsa_circ_0002320 for CRC diagnosis. Finally, a bioinformatics analysis was performed to verify the effect of hsa_circ_0002320 on CRC prognosis.Expression levels of hsa_circ_0002320 were significantly decreased in CRC plasma (P < .05). The expression level of hsa_circ_0002320 was significantly correlated with OS time (P < .05). Higher hsa_circ_0002320 reflected significantly greater OS; the HR of high hsa_circ_0002320 was 0.161 (95% CI, 0.066-0.393; P = .000). The area under the ROC curve of hsa_circ_0002320 in CRC was 0.823, which was higher than for the carcinoembryogenic antigen (area under the curve = 0.764). Kaplan-Meier analysis showed that CRC patients with low expression of hsa_circ_0002320 exhibited poorer OS times than those with high expression.Hsa_circ_0002320 could be a novel, noninvasive diagnostic blood biomarker for CRC prognosis.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , RNA Circular/sangue , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Ann Surg ; 272(2): 342-351, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675548

RESUMO

BACKGROUND: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. METHOD: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. RESULTS: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. CONCLUSION: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Linfócitos/metabolismo , Adulto , Idoso , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
Ann Surg ; 272(2): 352-356, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675549

RESUMO

OBJECTIVE: To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). BACKGROUND: Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. METHODS: Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. RESULTS: Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors. CONCLUSION: Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
19.
Life Sci ; 257: 118126, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32707053

RESUMO

AIMS: Rab31, a Rab5 subfamily member, has emerged as a modulator of membrane trafficking. Our study serves to clarify the role and mechanism of Rab31 in colorectal carcinoma (CRC) pathogenesis. MATERIALS AND METHODS: The differential expression of Rab31 was examined in paired normal and cancerous colonic tissues by quantitative PCR, western blot and immunochemistry. The prognostic significance of Rab31 was analysed by univariate and multivariate survival analyses. We also investigated the effects of Rab31 on tumour growth in vitro. KEY FINDINGS: We observed that Rab31, which is related to histological differentiation in CRC, was markedly overexpressed in CRC cells. Moreover, patients who showed higher Rab31 levels had a shortened survival period relative to those with low Rab31 levels. Rab31 knockdown significantly downregulated cyclin D1, p-mTOR, and p-p70S6K expression. Moreover, the expression of Rab31-induced p-p70S6K was almost inhibited by rapamycin, a well-established inhibitor of mTOR. Similarly, rapamycin also significantly decreased the stimulatory effect of Rab31 on the expression of cyclin D1. SIGNIFICANCE: These findings suggested that Rab31 enhanced proliferation, promoted cell cycle progression, and inhibited apoptosis of colorectal carcinoma cells through the mTOR pathway.


Assuntos
Neoplasias Colorretais/metabolismo , Ciclina D1/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Idoso , Apoptose , Western Blotting , Células CACO-2 , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sobrevida , Regulação para Cima
20.
Lancet Oncol ; 21(8): 1023-1034, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702310

RESUMO

BACKGROUND: Since a national lockdown was introduced across the UK in March, 2020, in response to the COVID-19 pandemic, cancer screening has been suspended, routine diagnostic work deferred, and only urgent symptomatic cases prioritised for diagnostic intervention. In this study, we estimated the impact of delays in diagnosis on cancer survival outcomes in four major tumour types. METHODS: In this national population-based modelling study, we used linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15-84 years, diagnosed with breast, colorectal, and oesophageal cancer between Jan 1, 2010, and Dec 31, 2010, with follow-up data until Dec 31, 2014, and diagnosed with lung cancer between Jan 1, 2012, and Dec 31, 2012, with follow-up data until Dec 31, 2015. We use a routes-to-diagnosis framework to estimate the impact of diagnostic delays over a 12-month period from the commencement of physical distancing measures, on March 16, 2020, up to 1, 3, and 5 years after diagnosis. To model the subsequent impact of diagnostic delays on survival, we reallocated patients who were on screening and routine referral pathways to urgent and emergency pathways that are associated with more advanced stage of disease at diagnosis. We considered three reallocation scenarios representing the best to worst case scenarios and reflect actual changes in the diagnostic pathway being seen in the NHS, as of March 16, 2020, and estimated the impact on net survival at 1, 3, and 5 years after diagnosis to calculate the additional deaths that can be attributed to cancer, and the total years of life lost (YLLs) compared with pre-pandemic data. FINDINGS: We collected data for 32 583 patients with breast cancer, 24 975 with colorectal cancer, 6744 with oesophageal cancer, and 29 305 with lung cancer. Across the three different scenarios, compared with pre-pandemic figures, we estimate a 7·9-9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis, corresponding to between 281 (95% CI 266-295) and 344 (329-358) additional deaths. For colorectal cancer, we estimate 1445 (1392-1591) to 1563 (1534-1592) additional deaths, a 15·3-16·6% increase; for lung cancer, 1235 (1220-1254) to 1372 (1343-1401) additional deaths, a 4·8-5·3% increase; and for oesophageal cancer, 330 (324-335) to 342 (336-348) additional deaths, 5·8-6·0% increase up to 5 years after diagnosis. For these four tumour types, these data correspond with 3291-3621 additional deaths across the scenarios within 5 years. The total additional YLLs across these cancers is estimated to be 59 204-63 229 years. INTERPRETATION: Substantial increases in the number of avoidable cancer deaths in England are to be expected as a result of diagnostic delays due to the COVID-19 pandemic in the UK. Urgent policy interventions are necessary, particularly the need to manage the backlog within routine diagnostic services to mitigate the expected impact of the COVID-19 pandemic on patients with cancer. FUNDING: UK Research and Innovation Economic and Social Research Council.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias Colorretais/mortalidade , Infecções por Coronavirus/epidemiologia , Neoplasias Esofágicas/mortalidade , Neoplasias Pulmonares/mortalidade , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Pandemias , Análise de Sobrevida , Adulto Jovem
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