Clinical Correlates of Health Preference and Generic Health-related Quality of Life in Patients with Colorectal Neoplasms

Background: The aims of the study were to assess the health preference and health-related quality of life (HRQOL) in patients with colorectal neoplasms (CRN), and to determine the clinical correlates that significantly influence the HRQOL of patients. Methods: Five hundred and fifty-four CRN patients, inclusive of colorectal polyp or cancer, who attended the colorectal specialist outpatient clinic at Queen Mary Hospital in Hong Kong between October 2009 and July 2010, were included. Patients were interviewed with questionnaires on socio-demographic characteristics, and generic and health preference measures of HRQOL using the SF-12 and SF-6D Health Surveys, respectively. Clinical information on stage of disease at diagnosis, time since diagnosis, primary tumour site was extracted from electronic case record. Mean HRQOL and health preference scores of CRN patients were compared with age-sex matched controls from the Chinese general population using independent t-test. Multiple linear regression analyses were conducted to explore the associations of clinical characteristics with HRQOL measures with the adjustment of socio-demographic characteristics. Results: Cross-sectional data of 515 eligible patients responded to the whole questionnaires were included in outcome analysis. In comparison with age-sex matched normative values, CRN patients reported comparable physical-related HRQOL but better mental-related HRQOL. Amongst CRN patients, time since diagnosis was positively associated with health preference score whilst patients with rectal neoplasms had lower health preference and physical-related HRQOL scores than those with sigmoid neoplasms. Health preference and HRQOL scores were significantly lower in patients with stage IV colorectal cancer than those with other less severe stages, indicating that progressive decline from low-risk polyp to stage IV colorectal cancer was observed in HRQOL scores. Conclusion: In CRN patients, a more advanced stage of disease was associated with worse HRQOL scores. Despite potentially adverse effect of disease on physical-related HRQOL, the mental-related HRQOL of CRN patients were better than that of Chinese general population. © 2013 Wong et al.published_or_final_versio

Laparoscopic colorectal resections with and without routine mechanical bowel preparation: a comparative study

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Health-related quality of life and risk of colorectal cancer recurrence and All-cause death among advanced stages of colorectal cancer 1-year after diagnosis

Background: The study aimed to examine the association between health-related quality of life (HRQOL) assessed with overall survival (OS) and recurrence after diagnosis of colorectal cancer (CRC). Methods: Overall 160 patients with advanced stage CRC were recruited in an observational study and completed the generic and condition-specific HRQOL questionnaires at the colorectal specialist outpatient clinic in Hong Kong, between 10/2009 and 07/2010. Socio-demographic and clinical characteristics including duration since diagnosis, primary tumor location and treatment modality, were collected to serve as predictor variables in regression models. All-cause death or CRC recurrence was the event of interest. Association between HRQOL with OS was assessed using Cox regression. Association between HRQOL and CRC recurrence was further modeled by competing-risks regression adjusted for the competing-risks of death from any cause. Results: After a median follow-up of 23 months, there were 22 (16.1%) incidents of CRC recurrence and 15 (9.4%) deaths. Decreased physical functioning (hazard ratios, HR = 0.917, 95%CI:0.889-0.981) and general health of domains in SF-12 (HR = 0.846, 95%CI:0.746-0.958) or SF-6D scores (HR = 0.010, 95%CI:0.000-0.573) were associated with an increased risk of death, with adjustment of patients' characteristics. Increased vitality (HR = 1.151, 95%CI:1.027-1.289) and mental health (HR = 1.128, 95%CI:1.005-1.265) were associated with an increased likelihood of death. In models adjusted for competing-risk of death, those with worse HRQOL was not associated with increased risk of CRC recurrence. Conclusions: Although self-reported HRQOL was not a significant prognostic factor for CRC recurrence, the HRQOL provided independent prognostic value about mortality in patients with advanced stage of CRC.published_or_final_versio

Psychometric assessment of the Chinese version of the Supportive Care Needs Survey short-form (SCNS-SF34-C) among Hong Kong and Taiwanese Chinese colorectal cancer patients

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Plasma Bmil mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

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The clinicopathological significance of miR-133a in colorectal cancer

This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient's clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson's method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (γ=-0.23), whereas CAV1 exhibited a significant positive correlation (γ=0.27), and a stronger correlation was found in patients who developed distant metastases (γ=0.42). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis. © 2014 Timothy Ming-Hun Wan et al.published_or_final_versio

Preclinical analysis of the anti-tumor and anti-metastatic effects of Raf265 on colon cancer cells and CD26(+) cancer stem cells in colorectal carcinoma

© 2015 Chow et al.Background: In colorectal carcinoma (CRC), activation of the Raf/MEK/ERK signaling pathway is commonly observed. In addition, the commonly used 5FU-based chemotherapy in patients with metastatic CRC was found to enrich a subpopulation of CD26+ cancer stem cells (CSCs). As activation of the Raf/MEK/ERK signaling pathway was also found in the CD26+ CSCs and therefore, we hypothesized that an ATP-competitive pan-Raf inhibitor, Raf265, is effective in eliminating the cancer cells and the CD26+ CSCs in CRC patients. Methods: HT29 and HCT116 cells were treated with various concentrations of Raf265 to study the anti-proliferative and apoptotic effects of Raf265. Anti-tumor effect was also demonstrated using a xenograft model. Cells were also treated with Raf265 in combination with 5FU to demonstrate the anti-migratory and invasive effects by targeting on the CD26+ CSCs and the anti-metastatic effect of the combined treatment was shown in an orthotopic CRC model. Results: Raf265 was found to be highly effective in inhibiting cell proliferation and tumor growth through the inhibition of the RAF/MEK/ERK signaling pathway. In addition, anti-migratory and invasive effect was found with Raf265 treatment in combination with 5FU by targeting on the CD26+ cells. Finally, the anti-tumor and anti-metastatic effect of Raf265 in combination with 5FU was also demonstrated. Conclusions: This preclinical study demonstrates the anti-tumor and anti-metastatic activity of Raf265 in CRC, providing the basis for exploiting its potential use and combination therapy with 5FU in the clinical treatment of CRC.published_or_final_versio

Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer

Aberrant levels of circulating microRNAs are potential biomarkers for the early detection of colorectal cancer. The aim of this study was to study miR-139-3p and miR-622 in serum as a non-invasive biomarker for colorectal cancer diagnosis. We applied quantitative polymerase chain reaction to determine the levels of miR-139-3p and miR-622 in 42 pairs of tumor and adjacent non-tumor tissues, and in serum samples of 117 patients and 90 control subjects. Our results showed that miR-139-3p was silenced whereas miR-622 was overexpressed in colorectal cancer. Similarly, serum miR-139-3p level was significantly lower in colorectal cancer patients than in control subjects whereas miR-622 was more frequently detectable in patients. ROC analysis showed that AUC of miR-139-3p was 0.9935, with a sensitivity of 96.6% and specificity of 97.8%. Serum miR-139-3p level showed high sensitivity and specificity for both early and late stage CRCs and proximal and distal CRCs. Detectable serum miR-622 showed a sensitivity of 87.5% and specificity of 63.5% for discriminating CRC patients, but the sensitivity dropped for late stage patients (72.7%). We also included analyses of the blood CEA level for comparing the diagnostic performance of these blood-based biomarkers. The median level in CRC patients (3.6 ng/ml) was significantly higher than that in control (1.8 ng/ml). The AUC value of CEA in diagnosing CRC patients was 0.7515. CEA showed a positive correlation with tumor stage and age of patients and its level was higher in male. Collectively, serum miR-139-3p has strong potential as a promising non-invasive biomarker in colorectal cancer detection.published_or_final_versio

Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer

Aberrant levels of circulating microRNAs are potential biomarkers for the early detection of colorectal cancer. The aim of this study was to study miR-139-3p and miR-622 in serum as a non-invasive biomarker for colorectal cancer diagnosis. We applied quantitative polymerase chain reaction to determine the levels of miR-139-3p and miR-622 in 42 pairs of tumor and adjacent non-tumor tissues, and in serum samples of 117 patients and 90 control subjects. Our results showed that miR-139-3p was silenced whereas miR-622 was overexpressed in colorectal cancer. Similarly, serum miR-139-3p level was significantly lower in colorectal cancer patients than in control subjects whereas miR-622 was more frequently detectable in patients. ROC analysis showed that AUC of miR-139-3p was 0.9935, with a sensitivity of 96.6% and specificity of 97.8%. Serum miR-139-3p level showed high sensitivity and specificity for both early and late stage CRCs and proximal and distal CRCs. Detectable serum miR-622 showed a sensitivity of 87.5% and specificity of 63.5% for discriminating CRC patients, but the sensitivity dropped for late stage patients (72.7%). We also included analyses of the blood CEA level for comparing the diagnostic performance of these blood-based biomarkers. The median level in CRC patients (3.6 ng/ml) was significantly higher than that in control (1.8 ng/ml). The AUC value of CEA in diagnosing CRC patients was 0.7515. CEA showed a positive correlation with tumor stage and age of patients and its level was higher in male. Collectively, serum miR-139-3p has strong potential as a promising non-invasive biomarker in colorectal cancer detection.published_or_final_versio

Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer

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