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1.
JAMA Netw Open ; 4(9): e2124483, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34495337

RESUMO

Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.


Assuntos
Neoplasias Colorretais/patologia , Controle de Doenças Transmissíveis/organização & administração , Aceitação pelo Paciente de Cuidados de Saúde , Carga Tumoral , Adulto , Idoso , Biomarcadores Tumorais/genética , COVID-19/epidemiologia , DNA Tumoral Circulante/sangue , Ensaios Clínicos Fase II como Assunto , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Estudos Controlados Antes e Depois , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
2.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360768

RESUMO

Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and extended surgery. The clinical usefulness of inflammation-related prognostic biomarkers available from routine blood examination has been reported in many types of cancer, e.g., neutrophil-lymphocyte ratio (NLR), lymphocyte-C-reactive protein ratio (LCR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and so on. Moreover, some scoring systems based on circulating blood cell counts and albumin concentration have been also reported to predict cancer patients' prognosis, such as the Glasgow prognostic score (GPS), systemic inflammation score (SIS), and prognostic nutritional index (PNI). The optimal biomarker and optimal cutoff value of the markers can be different depending on the cancer type. In this review, we summarize the prognostic impact of each inflammation-related marker in CRC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Contagem de Leucócitos , Avaliação Nutricional , Valor Preditivo dos Testes , Prognóstico
3.
Anticancer Res ; 41(7): 3615-3624, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230158

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the efficacy and safety of adjuvant chemotherapy in elderly patients with stage III colorectal cancer in a real-world setting. PATIENTS AND METHODS: A total of 165 patients of ≥70 years of age with stage III colorectal cancer who underwent a curative operation between 2008 and 2020 were enrolled in this study. RESULTS: Among septuagenarians, the relapse-free and overall survival rates in the single-agent therapy group and the combination therapy group were significantly better than those in the group treated by surgery alone. However, no significant differences were observed in the relapse-free and overall survival rates of the single-agent therapy group and the combination therapy group. Among octogenarians in whom all regimens were single-agent therapy, adjuvant chemotherapy tended to improve the relapse-free and overall survival rates but not the time to recurrence or cancer-specific survival. CONCLUSION: Single-agent adjuvant chemotherapy may be a useful treatment option for septuagenarians with stage III colorectal cancer. However, the efficacy of adjuvant chemotherapy in octogenarians was not shown in this study.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Taxa de Sobrevida
4.
Ann Ital Chir ; 92: 283-292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34312330

RESUMO

BACKGROUND/OBJECTIVE: In this study, we aimed to determine the relationship between HALP score and postoperative complications (According to Clavien-Dindo classification 3 and above), in patients with colo-rectal cancer who underwent curative surgical resection and to determine its clinical value in predicting prognosis. METHODS: 279 patients who underwent curative surgery for colorectal cancer between 2015-2018 were included in the study. The HALP value was calculated by dividing the product of hemoglobin (g/L), albumin (g/L), lymphocytes (/ L) by the number of platelets (/ L). In order to generate a cut off value for the HALP value, ROC analysis and ROC curve were created. The patients were divided into two groups according to survival, and cut off value was found by ROC analysis: Group 1 (Low HALP) and Group 2 (High HALP). Demographic, clinical characteristics, intraoperative , postoperative results and mean survival were compared between the groups. RESULTS: The patients were divided into two groups according to cut off value of 15.73. Group 1 consisted of 113 patients; Group 2 consisted of 166 patients. Average age was similar in the groups (62vs61, p:0.480). Patients in Group 1 received more neoadjuvant therapy (31%vs21%, p:0.064). CEA levels were higher in Group 1 (7.6vs4.3 p:0.034). Mucinous adenocarcinoma histological type was more common in Group 1 (24%vs13% ,p:0.040). Pathological grade poorly differentiated was more common in Group 1 (27%vs13%). Postoperative outcomes was similar to groups We found the HALP score as a risk factor for survival in multivariate analysis (HR=0.8552 95% (CI:0.6575-1.1125, p:0.007). If the HALP value is below 15.73, it is assumed that the average survival is 28 months with 45.4% sensitivity and 66.938% specificity. CONCLUSION: Our results showed that the HALP score is closely related to clinic pathological features and is an independent prognostic factor for survival. Its value in estimating mean survival is limited. KEY WORDS: Colorectal cancer, HALP score, Immunity, Nutrition.


Assuntos
Neoplasias Colorretais , Hemoglobinas/análise , Contagem de Linfócitos , Contagem de Plaquetas , Albumina Sérica/análise , Plaquetas , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Linfócitos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
5.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208547

RESUMO

BACKGROUND: Granulin is a secreted, glycosylated peptide-originated by cleavage from a precursor protein-which is involved in cell growth, tumor invasion and angiogenesis. However, the specific prognostic impact of granulin in human colorectal cancer has only been studied to a limited extent. Thus, we wanted to assess the expression of granulin in colorectal cancer patients to evaluate its potential as a prognostic biomarker. METHODS: Expressional differences of granulin in colorectal carcinoma tissue (n = 94) and corresponding healthy colon mucosa were assessed using qRT-PCR. Immunohistochemistry was performed in colorectal cancer specimens (n = 97), corresponding healthy mucosa (n = 47) and colorectal adenomas (n = 19). Subsequently, the results were correlated with histopathological and clinical patients' data. HCT-116 cells were transfected with siRNA for invasion and migration assays. RESULTS: Immunohistochemistry and qRT-PCR revealed tumoral over expression of granulin in colorectal cancer specimens compared to corresponding healthy colon mucosa and adenomas. Tumoral overexpression of granulin was associated with a significantly impaired overall survival. Moreover, downregulation of granulin by siRNA significantly diminished the invasive capacities of HCT-116 cells in vitro. CONCLUSION: Expression of granulin differs in colorectal cancer tissue, adenomas and healthy colon mucosa. Furthermore, granulin features invasive and migrative capabilities and overexpression of granulin correlates with a dismal prognosis. This reveals its potential as a prognostic biomarker and granulin could be a worthwhile molecular target for individualized anticancer therapy.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Granulinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Feminino , Expressão Gênica , Granulinas/genética , Células HCT116 , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
6.
J Surg Oncol ; 124(5): 791-800, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34196000

RESUMO

BACKGROUND: Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score. METHODS: A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS. RESULTS: Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p < .001). In the multivariate Cox model, a high OLGS was an independent predictor of 5-year OS (p < .001), and the hazard ratio (HR) of the OLGS-high group (HR = 7.171) was higher than that of the high clinical risk score group (HR = 4.337). CONCLUSION: The OLGS, a simple and handy scoring system, better predicts the 5-year OS of patients with CRLMs after hepatectomy and warrants prospective validation.


Assuntos
Neoplasias Colorretais/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Software , Taxa de Sobrevida
7.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202896

RESUMO

The human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic driver and a successful therapeutic target in several malignancies, such as breast and gastric cancers. HER2 alterations, including amplification and somatic mutations, have also been detected in a small but not negligible subset of patients affected by advanced colorectal cancer (aCRC). However, to date, there are no available oncotargets in this malignancy beyond RAS and BRAF that are available. Here we present an overview on the present predictive and prognostic role of HER2 expression in aCRC, as well as on its consequent potential therapeutic implications from preclinical investigations towards ongoing trials testing anti-HER2 agents in aCRC. While HER2's role as a molecular predictive biomarker for anti-EGFR therapies in CRC is recognized, HER2 prognostic value remains controversial. Moreover, thanks to the impressive and growing body of clinical evidence, HER2 is strongly emerging as a new potential actionable oncotarget in aCRC. In conclusion, in the foreseeable future, HER2-targeted therapeutic strategies may integrate the algorithm of aCRC treatment towards an increasingly tailored therapeutic approach to this disease.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/etiologia , Proteínas Proto-Oncogênicas B-raf/genética , Receptor ErbB-2/genética , Proteínas ras/genética , Animais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Prognóstico , Proteínas Proto-Oncogênicas B-raf/metabolismo , Receptor ErbB-2/metabolismo , Transdução de Sinais , Proteínas ras/metabolismo
8.
Anticancer Res ; 41(8): 3905-3915, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281853

RESUMO

BACKGROUND/AIM: Primary tumor location and RAS and BRAF V600E mutations are predictors of the efficacy of epidermal growth factor receptor (EGFR) inhibitors. However, there are limited reports on their effects on the outcomes of third-line chemotherapy with EGFR inhibitors in metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: We retrospectively collected the clinical data of KRAS exon 2 wild type (WT) mCRC patients treated with EGFR inhibitor monotherapy or EGFR inhibitor plus irinotecan as third-line chemotherapy. The association between primary tumor location, RAS (KRAS exon 3, 4 or NRAS), BRAF V600E, and PIK3CA mutational status, and treatment outcome was evaluated. RESULTS: A total of 72 patients were included in this study. In multivariate analysis, RAS (p=0.004) and BRAF mutations (p=0.00008) were independent factors for shorter PFS. Poor performance status (p=0.01) and BRAF mutation (p=0.00002) were independent factors for shorter OS, whereas primary tumor location and PIK3CA mutation did not influence survival. CONCLUSION: Additional analysis of RAS and BRAF mutations could contribute to the selection of patients who are likely to benefit from third-line EGFR inhibitors, regardless of primary tumor location.


Assuntos
Antineoplásicos/uso terapêutico , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais , Receptores ErbB/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Resultado do Tratamento
9.
Biomed Pharmacother ; 140: 111759, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091180

RESUMO

Colorectal cancer (CRC) is the third most fatal and fourth most frequently diagnosed neoplasm in the world. Numerous non-coding RNAs have been shown to contribute in the development of CRC. MicroRNAs (miRNAs) are among the mostly assessed non-coding RNAs in CRC. These transcripts influence expression and activity of TGF-ß, Wnt/ß-catenin, MAPK, PI3K/AKT and other CRC-related pathways. In the context of CRC, miRNAs interact with long non-coding RNAs to influence CRC course. Stool and serum levels of miRNAs have been used to distinguish CRC patients from healthy controls, indicating diagnostic roles of these transcripts in CRC. Therapeutic application of miRNAs in CRC has been assessed in animal models, yet has not been verified in clinical settings. In the current review, we have provided a recent update on the role of miRNAs in CRC development as well as diagnostic and prognostic approaches.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Humanos , Polimorfismo Genético , Prognóstico
10.
J Surg Oncol ; 124(4): 598-606, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34061356

RESUMO

BACKGROUND: Phosphorylated mammalian target of rapamycin (p-mTOR) plays a crucial role in the process of cancer progression. Common gene mutations of colorectal cancer lead to the activation of the PI3k/Akt/mTOR pathway. In this study, we determined whether p-mTOR expression in colorectal liver metastases is a predictive marker of prognosis following liver resection. METHODS: Eighty-one patients with colorectal liver metastases who had undergone curative resection were evaluated using immunohistochemistry of p-mTOR. Data regarding clinicopathological features and patient survival were analyzed. RESULTS: The p-mTOR expression in colorectal liver metastases was detected in 55 (67.9%) patients. Patients whose metastases had high p-mTOR expression showed a significantly lower overall survival rate after resection as compared to patients with low p-mTOR expression (p = 0.016), while there was no significant difference in the disease-free survival between the two groups. Repeat resection for recurrence was performed more frequently in patients with p-mTOR positive than others (p = 0.024). Multivariate analysis showed that p-mTOR expression was an independent prognostic factor of overall survival after liver resection (p = 0.019). CONCLUSIONS: mTOR was frequently activated in colorectal liver metastases, and the p-mTOR expression was a biological marker for predicting the overall survival of patients with colorectal liver metastases following liver resection.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Serina-Treonina Quinases TOR/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Fosforilação , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Serina-Treonina Quinases TOR/genética
11.
Nat Biomed Eng ; 5(7): 678-689, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34183802

RESUMO

Assays for cancer diagnosis via the analysis of biomarkers on circulating extracellular vesicles (EVs) typically have lengthy sample workups, limited throughput or insufficient sensitivity, or do not use clinically validated biomarkers. Here we report the development and performance of a 96-well assay that integrates the enrichment of EVs by antibody-coated magnetic beads and the electrochemical detection, in less than one hour of total assay time, of EV-bound proteins after enzymatic amplification. By using the assay with a combination of antibodies for clinically relevant tumour biomarkers (EGFR, EpCAM, CD24 and GPA33) of colorectal cancer (CRC), we classified plasma samples from 102 patients with CRC and 40 non-CRC controls with accuracies of more than 96%, prospectively assessed a cohort of 90 patients, for whom the burden of tumour EVs was predictive of five-year disease-free survival, and longitudinally analysed plasma from 11 patients, for whom the EV burden declined after surgery and increased on relapse. Rapid assays for the detection of combinations of tumour biomarkers in plasma EVs may aid cancer detection and patient monitoring.


Assuntos
Neoplasias Colorretais/diagnóstico , Técnicas Eletroquímicas/métodos , Vesículas Extracelulares/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Molécula de Adesão da Célula Epitelial/sangue , Molécula de Adesão da Célula Epitelial/metabolismo , Vesículas Extracelulares/imunologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Recidiva , Adulto Jovem
12.
Am J Surg Pathol ; 45(7): 969-978, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34105518

RESUMO

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly have an independent impact on patient prognosis. We reclassified a large single-center cohort of 1004 CRCs spanning 2 decades for adjusted WHO grade (low vs. high), tumor budding (Bd1/Bd2/Bd3), and CRC subtype (adenocarcinoma not otherwise specified, micropapillary, mucinous, serrated, medullary, adenoma-like, signet-ring cell, mixed adenoneuroendocrine carcinoma/neuroendocrine carcinoma, undifferentiated) according to the criteria of the 2019 WHO classification. We investigated the interaction of these parameters, their connection to stage/microsatellite status, and their significance for patient survival in the different subgroups. Specific subtypes other than adenocarcinoma not otherwise specified represented one third of all CRCs and were unevenly distributed throughout stage and microsatellite subgroups. Subtypes, WHO grade and tumor budding profoundly impacted all survival parameters (P<0.001 for all analyses), with CRC subtypes and tumor budding-but not WHO grade-being stage-independent prognosticators for all survival comparisons. WHO grade had very limited prognostic value in CRC subtypes, while tumor budding retained its strong prognostic impact in most scenarios. Accurate delineation of CRC subtypes introduced in the 2019 WHO classification provides strong stage-independent prognostic information, arguing that they should be considered in pathology reports and in clinical trials. Of the morphology-based grading schemes included in the 2019 WHO, tumor budding outperforms WHO grade.


Assuntos
Carcinoma/patologia , Movimento Celular , Neoplasias Colorretais/patologia , Idoso , Biópsia , Carcinoma/classificação , Carcinoma/mortalidade , Carcinoma/cirurgia , Colectomia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Organização Mundial da Saúde
13.
Nutrients ; 13(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064893

RESUMO

The prognostic nutritional index (PNI) has been reported to be associated with postoperative complications and prognosis in cancer surgery. However, few studies have evaluated the association between preoperative PNI and postoperative acute kidney injury (AKI) in colorectal cancer patients. This study evaluated association of preoperative PNI and postoperative AKI in patients who underwent colorectal cancer surgery. This study retrospectively analyzed 3543 patients who underwent colorectal cancer surgery between June 2008 and February 2012. The patients were classified into four groups by the quartile of PNI: Q1 (≤43.79), Q2 (43.79-47.79), Q3 (47.79-51.62), and Q4 (≥51.62). Multivariate regression analysis was performed to assess the risk factors for AKI and 1-year mortality. AKI was defined according to Kidney Disease Improving Global Outcomes classification (KDIGO) criteria. Additionally, we assessed surgical outcomes such as hospital stay, ICU admission, and postoperative complications. The incidence of postoperative AKI tended to increase in the Q1 group (13.4%, 9.2%, 9.4%, 8.8%). In the multivariate analysis, high preoperative PNI was significantly associated with low risk of postoperative AKI (adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93-0.99, p = 0.003) and low 1-year mortality (OR: 0.92, 95% CI: 0.86-0.98, p = 0.011). Male sex, body mass index, diabetes mellitus, and hypertension were risk factors for AKI. The Q1 (≤43.79) group had poor surgical outcomes, such as postoperative AKI (OR: 1.52, 95% CI: 1.18-1.95, p = 0.001), higher rates of ICU admission (OR: 3.13, 95% CI: 1.82-5.39, p < 0.001) and higher overall mortality (OR: 3.81, 95% CI: 1.86-7.79, p < 0.001). In conclusion, low preoperative PNI levels, especially in the Q1 (≤43.79), were significantly associated with postoperative AKI and surgical outcomes, such as hospital stay, postoperative ICU admission, and mortality.


Assuntos
Injúria Renal Aguda/etiologia , Neoplasias Colorretais , Avaliação Nutricional , Injúria Renal Aguda/mortalidade , Idoso , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Incidência , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
14.
Int J Cancer ; 149(8): 1553-1563, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34164808

RESUMO

There are limited population-based survival data for colorectal cancer (CRC) in sub-Saharan Africa. Here, 1707 persons diagnosed with CRC from 2005 to 2015 were randomly selected from 13 population-based cancer registries operating in 11 countries in sub-Saharan Africa. Vital status was ascertained from medical charts or through next of kin. 1-, 3- and 5-year overall and relative survival rates for all registries and for each registry were calculated using the Kaplan-Meier estimator. Multivariable analysis was used to examine the associations of 5-year relative survival with age at diagnosis, stage and country-level Human Development Index (HDI). Observed survival for 1448 patients with CRC across all registries combined was 72.0% (95% CI 69.5-74.4%) at 1 year, 50.4% (95% CI 47.6-53.2%) at 3 years and 43.5% (95% CI 40.6-46.3%) at 5 years. We estimate that relative survival at 5 years in these registry populations is 48.2%. Factors associated with poorer survival included living in a country with lower HDI, late stage at diagnosis and younger or older age at diagnosis (<50 or ≥70 years). For example, the risk of death was 1.6 (95% CI 1.2-2.1) times higher for patients residing in medium-HDI and 2.7 (95% CI 2.2-3.4) times higher for patients residing in low-HDI compared to those residing in high-HDI countries. Survival for CRC remains low in sub-Saharan African countries, though estimates vary considerably by HDI. Strengthening health systems to ensure access to prevention, early diagnosis and appropriate treatment is critical in improving outcomes of CRC in the region.


Assuntos
Neoplasias Colorretais/mortalidade , Sistema de Registros/estatística & dados numéricos , África ao Sul do Saara/epidemiologia , Fatores Etários , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida
15.
Cancer Sci ; 112(9): 3732-3743, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34118099

RESUMO

Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular-based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating ß-catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/ß-catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Progressão da Doença , Receptores de Dopamina D2/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , beta Catenina/metabolismo , Idoso , Animais , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Antagonistas de Dopamina/farmacologia , Feminino , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Pimozida/farmacologia , Interferência de RNA , Receptores de Dopamina D2/genética , Transdução de Sinais , Taxa de Sobrevida , Transfecção , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Medicine (Baltimore) ; 100(20): e25793, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011041

RESUMO

ABSTRACT: Preoperative pulmonary function assessment is applied to select surgical candidates and predict the occurrence of postoperative complications. This present study enrolled 2323 colorectal cancer patients. Forced vital capacity (FVC) and maximal voluntary ventilation (MVV) were measured as predicted values. Associations between patient pulmonary function and both prognosis and postoperative complications was analyzed. The value of FVC and MVV optimal cutoff was 98.1 (P < .001) and 92.5 (P < .001), respectively. Low FVC and low MVV were associated with higher rates of postoperative fever (23.8% vs 13.9%, P < .001; 17.8% vs 13.3%, P = .049, respectively) and with higher rates of pneumonia (3.75% vs 1.73%, P = .002; 3.00% vs 1.71%, P = .009, respectively), pleural effusion (3.00% vs 1.57%, P = .033; 3.18% vs 1.42%, P = .006, respectively), and poor patient prognosis (5-year overall survival: 80.0% vs 90.3%, P < .001; 71.7% vs 91.9%, P < .001, respectively). In addition, low FVC was closely related to the higher rate of anastomosis leak (4.31% vs 2.29%, P = .013), low MVV was correlated with the higher rate of uroschesis (2.38% vs 0.65%, P < .001). In subgroup analyses, the predictive value of FVC and MVV in patients with different tumor stage was analyzed. Both low FVC and MVV were independent risk factors for poor prognosis in stage II and III, indicating that low FVC and MVV are predictive of poorer prognosis and higher risk of postoperative complications in colorectal cancer patients.


Assuntos
Colectomia/efeitos adversos , Neoplasias Colorretais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Protectomia/efeitos adversos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Febre/epidemiologia , Febre/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Ventilação Voluntária Máxima , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Derrame Pleural/epidemiologia , Derrame Pleural/etiologia , Pneumonia/epidemiologia , Pneumonia/etiologia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Capacidade Vital , Adulto Jovem
17.
Biomed Pharmacother ; 140: 111721, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34015582

RESUMO

Circular RNAs (circRNAs) comprise a group of noncoding RNAs with a circular conformation being constructed by either classic spliceosome-mediated or lariat-kind of splicing. They have tissue and temporal specificity and are involved in different biological functions. A vast body of literature has demonstrated critical roles of circRNAs in the formation or progression of neoplasms. Hsa_circ_0066631, hsa_circ_0082096, ciRS-7, circMAT2B, circ_052666, circMBOAT2, circPACRGL and circ_0128846 are among up-regulated circRNAs in CRC. Instead, expression levels of circTADA2A, circ_022743, circ_004452, circ-FBXW7, circ0106714, circFNDC3B and circ_cse1 have been decreased in CRC samples. Finally, expression levels of circRNA-100876, hsa_circ_0002320, circNOL10, circ_0056618, circ_0060745, circ-0004277, hsa_circRNA_102958, circPPP1R12A, hsa_circ_0007534, circ_0079993 and hsa_circ_0005075 can be used for prediction of clinical outcome of patients CRC.


Assuntos
Neoplasias Colorretais/genética , RNA Circular , Animais , Neoplasias Colorretais/mortalidade , Regulação para Baixo , Humanos , Prognóstico , Regulação para Cima
18.
JAMA ; 325(19): 1978-1998, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34003220

RESUMO

Importance: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US. Objective: To systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021. Study Selection: English-language studies conducted in asymptomatic populations at general risk of CRC. Data Extraction and Synthesis: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted. Main Outcomes and Measures: Colorectal cancer incidence and mortality, test accuracy in detecting cancers or adenomas, and serious adverse events. Results: The review included 33 studies (n = 10 776 276) on the effectiveness of screening, 59 (n = 3 491 045) on the test performance of screening tests, and 131 (n = 26 987 366) on the harms of screening. In randomized clinical trials (4 trials, n = 458 002), intention to screen with 1- or 2-time flexible sigmoidoscopy vs no screening was associated with a decrease in CRC-specific mortality (incidence rate ratio, 0.74 [95% CI, 0.68-0.80]). Annual or biennial guaiac fecal occult blood test (gFOBT) vs no screening (5 trials, n = 419 966) was associated with a reduction of CRC-specific mortality after 2 to 9 rounds of screening (relative risk at 19.5 years, 0.91 [95% CI, 0.84-0.98]; relative risk at 30 years, 0.78 [95% CI, 0.65-0.93]). In observational studies, receipt of screening colonoscopy (2 studies, n = 436 927) or fecal immunochemical test (FIT) (1 study, n = 5.4 million) vs no screening was associated with lower risk of CRC incidence or mortality. Nine studies (n = 6497) evaluated the test accuracy of screening computed tomography (CT) colonography, 4 of which also reported the test accuracy of colonoscopy; pooled sensitivity to detect adenomas 6 mm or larger was similar between CT colonography with bowel prep (0.86) and colonoscopy (0.89). In pooled values, commonly evaluated FITs (14 studies, n = 45 403) (sensitivity, 0.74; specificity, 0.94) and stool DNA with FIT (4 studies, n = 12 424) (sensitivity, 0.93; specificity, 0.85) performed better than high-sensitivity gFOBT (2 studies, n = 3503) (sensitivity, 0.50-0.75; specificity, 0.96-0.98) to detect cancers. Serious harms of screening colonoscopy included perforations (3.1/10 000 procedures) and major bleeding (14.6/10 000 procedures). CT colonography may have harms resulting from low-dose ionizing radiation. It is unclear if detection of extracolonic findings on CT colonography is a net benefit or harm. Conclusions and Relevance: There are several options to screen for colorectal cancer, each with a different level of evidence demonstrating its ability to reduce cancer mortality, its ability to detect cancer or precursor lesions, and its risk of harms.


Assuntos
Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Sangue Oculto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Colonoscopia/métodos , Neoplasias Colorretais/mortalidade , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Risco , Sigmoidoscopia , Tomografia Computadorizada por Raios X
19.
Cancer Epidemiol ; 73: 101937, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33941483

RESUMO

OBJECTIVE: To evaluate the impact of a colorectal cancer (CRC) risk predicting system on CRC mortality rates. METHOD: An organized population screening program targeted at all the subjects (n = 102,076) at age 40-74 in nine towns of Jiashan county, China was conducted from 2007 to 2012. All of the screening participants were first triaged into high-risk & low-risk groups by a questionnaire and two fecal immunuochemical tests, only the high-risk subjects were subject to colonocopy. The screening participants were surveyed death caused by CRC for a total of six years after the enrollment. The CRC mortality in subgroups of the screening population was analyzed. RESULTS: A total of 82,184 (80.51 % of the targeted population) screening participants were identified. CRC death were recorded for 142 subjects (28.819 per 105 person-years). The age-adjusted relative risk(RR) of CRC death in the high-risk subjects (n = 12862, 84.48 per 105 person-years) was 3.92 (95 % CI = 2.81-5.49) compared with the low-risk subjects (n = 69322, 18.52 per 105 person-years). In the high-risk group, the age-adjusted RR of CRC death for those accepted colonoscopies (51.44 per 105 person-years) compared with those refused colonoscopies (187.94 per 105 person-years, P < 0.0001) was 0.34 (95 % CI = 0.21-0.56). The first three years after screening has seen the largest difference of CRC death hazard in both comparing groups. CONCLUSION: The high-risk subjects triaged by the risk predicting system have a higher CRC mortality rate than the low-risk subjects, especially in the first three years after screening. Refusal of colonoscopy is risky behavior for the high-risk subject.


Assuntos
Colonoscopia , Neoplasias Colorretais , Detecção Precoce de Câncer , Vigilância da População , Adulto , Idoso , China/epidemiologia , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/mortalidade , Detecção Precoce de Câncer/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Medição de Risco
20.
Cancer Epidemiol ; 73: 101962, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34051687

RESUMO

BACKGROUND: It is established that comorbidities negatively influence colorectal cancer (CRC)-specific survival. Only few studies have used the relative survival (RS) setting to estimate this association, although RS has been proven particularly useful considering the inaccuracy in death certification. This study aimed to investigate the impact of non-cancer comorbidities at CRC diagnosis on net survival, using cancer registry data. METHODS: We included 1076 CRC patients diagnosed between 2000 and 2001 in the canton of Zurich. The number and severity of comorbidities was expressed using the Charlson Comorbidity Index (CCI). Multiple imputation was performed to account for missing information and 10-year net survival was estimated by modeling the excess hazards of death due to CRC, using flexible parametric models. RESULTS: After imputation, approximately 35 % of the patients were affected by comorbidities. These appeared to decrease the 10-year net survival; the estimated excess hazard ratio for patients with one mild comorbidity was 2.14 (95 % CI 1.60-2.86), and for patients with one more severe or more than one comorbidity was 2.43 (95 % CI 1.77-3.34), compared to patients without comorbidities. CONCLUSIONS: Our analysis suggested that non-cancer comorbidities at CRC diagnosis significantly decrease the 10-year net survival. Future studies should estimate net survival of CRC including comorbidities as prognostic factor and use a RS framework to overcome the uncertainty in death certification.


Assuntos
Neoplasias Colorretais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Comorbidade , Humanos , Análise de Sobrevida
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