Psychological distress and quality of life following positive fecal occult blood testing in colorectal cancer screening.
- 作者列表："Vermeer NCA","van der Valk MJM","Snijders HS","Vasen HFA","van der Hoop AG","Guicherit OR","Liefers GJ","van de Velde CJH","Stiggelbout AM","Peeters KCMJ
OBJECTIVE:This study aimed to assess psychological functioning, quality of life, and regret about screening after a positive FIT and subsequent colonoscopy, and to evaluate changes over time. METHODS:This is a prospective cohort study. Individuals aged 55-75 with a positive Fecal Immunochemical Test (FIT) that were referred for colonoscopy between July 2017 and November 2018, were invited to complete questionnaires related to psychological distress and health-related quality of life at three pre-defined time points: before colonoscopy, after histopathology result notification, and after 6 months. Four questionnaires were used: the Psychological Consequences Questionnaire (PCQ), the 6-item Cancer Worry Scale (CWS), the Decision Regret Scale (DRS), and the 36-item Short-Form (SF-36). RESULTS:A total of 1066 participants out of 2151 eligible individuals were included. Patients with cancer showed a significant increase in psychological dysfunction (P = 0.01) and cancer worry (P = 0.008) after colonoscopy result notification, and a decline to pre-colonoscopy measurements after six months. In the no-cancer groups, psychological dysfunction and cancer worry significantly decreased over time (P < 0.05) but there was no ongoing decline. After six months, 17% of participants with no cancer experienced high level of cancer worry (CWS ≥ 10). Yet, only 5% reported high level of regret about screening participation (DRS > 25). A good global quality of life was reported in participants with no cancer. CONCLUSION:Some psychological distress remains up to six months after colonoscopy in participants who tested false-positive in the Dutch bowel cancer screening program. This article is protected by copyright. All rights reserved.
目的: 本研究旨在评估积极配合和随后结肠镜检查后的心理功能、生活质量和对筛查的遗憾，并评估随时间的变化。 方法: 这是一项前瞻性队列研究。2017年7月至 2018年11月期间转诊接受结肠镜检查的粪便免疫化学试验 (FIT) 阳性的 55-75 岁个体,被邀请在三个预定的时间点完成与心理困扰和健康相关生活质量相关的问卷调查: 结肠镜检查前、组织病理学结果通知后和 6 个月后。采用四份问卷: 心理后果问卷 (PCQ) 、 6 项癌症担忧量表 (CWS) 、决策后悔量表 (DRS) 、和 36 项的短形式 (SF-36)。 结果: 共纳入 1066 例合格个体中的 2151 例参与者。癌症患者在结肠镜检查结果通知后，心理功能障碍 (P = 0.01) 和癌症担忧 (P = 0.008) 显著增加,六个月后结肠镜检查前测量值下降。在非癌症组中，心理功能障碍和癌症担忧随时间显著下降 (P <0.05)，但没有持续下降。六个月后，17% 没有癌症的参与者经历了高水平的癌症担忧 (cws ≥ 10)。然而，只有 5% 的人报告了对筛查参与的高度遗憾 (drs> 25)。在没有癌症的参与者中报告了良好的全球生活质量。 结论: 在荷兰肠癌筛查项目中检测假阳性的参与者在结肠镜检查后 6 个月仍存在一些心理困扰。本文受版权保护。保留所有权利。
METHODS::Aims: Radiotherapy is predominantly used as one of the treatment modalities to treat local tumor in colorectal cancer (CRC). Hindrance in disease treatment can be attributed to radio-tolerance of cancer stem cells (CSCs) subsistence in the tumor. Understanding the radio-resistant property of CSCs might help in the accomplishment of targeted radiotherapy treatment and increased disease-free survival. Telomeric RAP1 contributes in modulation of various transcription factors leading to aberrant cell proliferation and tumor cell migration. Therefore, we investigated the role of RAP1 in maintaining resistance phenotype and acquired stemness in radio-resistant cells.Main Methods: Characterization of HCT116 derived radio-resistant cell (HCT116RR) was performed by cell survival and DNA damage profiling. RAP1 silenced cells were investigated for DNA damage and expression of CSC markers through western blotting and Real-time PCR post-irradiation. Molecular docking and co-immunoprecipitation study were performed to investigate RAP1 and KLF4 interaction followed by RAP1 protein status profiling in CRC patient.Key findings: We established radio-resistant cells, which showed tolerance to radiotherapy and elevated expression of CSC markers along with RAP1. RAP1 silencing showed enhanced DNA damage and reduced expression of CSC markers post-irradiation. We observed strong physical interaction between RAP1 and KLF4 protein. Furthermore, higher RAP1 expression was observed in the tumor of CRC patients. Dataset analysis also revealed that high expression of RAP1 expression is associated with poor prognosis.Significance: We conclude that higher expression ofRAP1 implicates its possible role in promoting radio-resistance in CRC cells by modulating DNA damage and CSC phenotype.
METHODS::Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 μM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.
METHODS:OBJECTIVES:Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial. MATERIALS AND METHODS:Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA. RESULTS:Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes. CONCLUSIONS:Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.