Wing Wa Leung

Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps

Objective The detection of molecular markers in stool samples is a potential strategy for colorectal cancer (CRC) screening. This study evaluated the feasibility of detecting miR-21 and miR-92a in stool samples of patients with CRC or polyps. Methods The reproducibility of detection and stability of stool-based microRNA were evaluated. Stool samples were collected from 88 patients with CRC, 57 patients with colorectal polyps and 101 healthy controls. MiRNA levels in CRC tissues and stool samples were detected by real-time quantitative reverse transcription PCR. Stool miR-21 and miR-92a levels were compared before and after the removal of tumour or advanced adenoma. Results The study demonstrated that stool-based miRNA were stable with highly reproducible detection. The expression of miR-21 and miR-92a was significantly higher in CRC tissues compared with their adjacent normal tissues (p<0.0001). Patients with CRC had a significantly higher stool miR-21 level (p<0.01) and miR-92a level (p<0.0001) compared with normal controls. Stool miR-92a, but not miR-21, was significantly higher in patients with polyps than in controls (p<0.0001). At a cut-off value of 435 copies/ng of stool RNA, miR-92a had a sensitivity of 71.6% and 56.1% for CRC and polyp, respectively, and a specificity of 73.3%. In addition, the stool miR-92a level demonstrated a higher sensitivity for distal CRC than proximal CRC (p<0.05), and a higher sensitivity for advanced adenoma than minor polyps (p<0.05). Removal of tumour resulted in reduced stool miR-21 and miR-92a levels (p<0.01), and the removal of advanced adenoma resulted in a reduction of the stool miR-92a level (p<0.05). Conclusion Stool miRNA are useful for screening CRC and polyps.

Identification of microRNA-135b in Stool as a Potential Noninvasive Biomarker for Colorectal Cancer and Adenoma

Purpose: Detecting microRNA (miRNA) in stool is a novel approach for colorectal cancer (CRC) screening. This study aimed to identify stool-based miRNA as noninvasive biomarkers for detection of CRC and adenoma. Experimental Design: A miRNA expression array covering 667 human miRNAs was performed on five pairs of CRC and two pairs of advanced adenoma tissues. The most upregulated miRNAs were validated in 40 pairs of CRC tissues, 16 pairs of advanced adenoma tissues, and 424 stool samples, including 104 CRCs, 169 adenomas, 42 inflammatory bowel diseases (IBD), and 109 healthy controls. miRNA levels were followed-up after removal of lesions. Results: In an array analysis, miR-31 and miR-135b were the most upregulated miRNAs in CRC and advanced adenoma as compared with their adjacent normal tissues (>13-fold increase). In stool samples, level of miR-135b was significantly higher in subjects with CRC (P < 0.0001) or adenomas (P < 0.0001), but not in patients with IBD compared with controls. miR-135b showed a significant increasing trend across the adenoma to cancer sequence (P < 0.0001). Levels of miR-31 were not significantly different among groups. The sensitivity of stool mR-135b was 78% for CRC, 73% for advanced adenoma, and 65% for any adenoma, respectively, with a specificity of 68%. No significant difference in the miR-135b level was found between proximal and distal colorectal lesions. Stool miR-135b dropped significantly upon removal of CRC or advanced adenoma (P < 0.0001). Conclusion: Stool-based miR-135b can be used as a noninvasive biomarker for the detection of CRC and advanced adenoma. Clin Cancer Res; 20(11); 2994–3002. ©2014 AACR.

Electroacupuncture Reduces Duration of Postoperative Ileus After Laparoscopic Surgery for Colorectal Cancer

BACKGROUND & AIMS We investigated the efficacy of electroacupuncture in reducing the duration of postoperative ileus and hospital stay after laparoscopic surgery for colorectal cancer. METHODS We performed a prospective study of 165 patients undergoing elective laparoscopic surgery for colonic and upper rectal cancer, enrolled from October 2008 to October 2010. Patients were assigned randomly to groups that received electroacupuncture (n = 55) or sham acupuncture (n = 55), once daily from postoperative days 1-4, or no acupuncture (n = 55). The acupoints Zusanli, Sanyinjiao, Hegu, and Zhigou were used. The primary outcome was time to defecation. Secondary outcomes included postoperative analgesic requirement, time to ambulation, and length of hospital stay. RESULTS Patients who received electroacupuncture had a shorter time to defecation than patients who received no acupuncture (85.9 ± 36.1 vs 122.1 ± 53.5 h; P < .001) and length of hospital stay (6.5 ± 2.2 vs 8.5 ± 4.8 days; P = .007). Patients who received electroacupuncture also had a shorter time to defecation than patients who received sham acupuncture (85.9 ± 36.1 vs 107.5 ± 46.2 h; P = .007). Electroacupuncture was more effective than no or sham acupuncture in reducing postoperative analgesic requirement and time to ambulation. In multiple linear regression analysis, an absence of complications and electroacupuncture were associated with a shorter duration of postoperative ileus and hospital stay after the surgery. CONCLUSIONS In a clinical trial, electroacupuncture reduced the duration of postoperative ileus, time to ambulation, and postoperative analgesic requirement, compared with no or sham acupuncture, after laparoscopic surgery for colorectal cancer. ClinicalTrials.gov number, NCT00464425.

Long-term oncologic outcomes of laparoscopic versus open surgery for rectal cancer: a pooled analysis of 3 randomized controlled trials.

Objective:To compare long-term oncologic outcomes between laparoscopic and open surgery for rectal cancer and to identify independent predictors of survival. Background:Few randomized trials comparing laparoscopic and open surgery for rectal cancer have reported long-term survival data. Methods:Data from the 3 randomized controlled trials comparing curative laparoscopic (n = 136) and open surgery (n = 142) for upper, mid, and low rectal cancer conducted at the Prince of Wales Hospital, Hong Kong, between September 1993 and August 2007 were pooled together for this analysis. Survival and disease status were updated to February 2012. Survival was calculated using the Kaplan-Meier method, and independent predictors of survival were determined using the Cox regression analysis. Results:The demographic data of the 2 groups were comparable. The median follow-up time of living patients was 124.5 months in the laparoscopic group and 136.6 months in the open group. At 10 years, there were no significant differences in locoregional recurrence (5.5% vs. 9.3%; P = 0.296), cancer-specific survival (82.5% vs. 77.6%; P = 0.443), and overall survival (63.0% vs. 61.1%; P = 0.505) between the laparoscopic and open groups. There was a trend toward lower recurrence rate at 10 years in the laparoscopic group than in the open group among patients with stage III cancer (P = 0.078). The Cox regression analysis showed that stage III cancer, lymphovascular permeation, and blood transfusion, but not the operative approach, were independent predictors of poorer cancer-specific survival. Conclusions:This pooled analysis with a follow-up of more than 10 years confirms the long-term oncologic safety of laparoscopic surgery for rectal cancer.

Emergency Laparoscopic-Assisted Versus Open Right Hemicolectomy for Complicated Cecal Diverticulitis: A Comparative Study

BACKGROUND Emergency open colectomy is generally agreed, by most surgeons, to be the treatment of choice for complicated cecal diverticulitis. However, the literature on the use of laparoscopy in treating this surgical emergency is scanty. This study aimed to evaluate the feasibility and safety of emergency laparoscopic-assisted right hemicolectomy for complicated cecal diverticulitis and to compare its operative and short-term clinical outcomes with the open approach. PATIENTS AND METHODS Between September 2001 and June 2006, 18 consecutive patients with an intraoperative diagnosis of complicated cecal diverticulitis underwent emergency right hemicolectomy at our institution, 6 with the laparoscopic-assisted approach and 12 with the open approach. Clinical data were retrospectively collected and compared between the two groups. RESULTS The demographic data of the two groups were comparable. The operative time was similar between the two groups, but the laparoscopic-assisted group had significantly less blood loss (35 vs. 100 mL; P = 0.041). Although the time to first bowel motion was significantly shorter in the laparoscopic-assisted group (3.5 vs. 5 days; P = 0.041), the time to full ambulation and the duration of hospital stay were not different between the two groups. More patients in the open group developed postoperative complications (50 vs. 33.3%), but the difference was not statistically significant. CONCLUSIONS With the availability of experienced laparoscopic surgeons, emergency laparoscopic-assisted right hemicolectomy can be safely performed in patients with complicated cecal diverticulitis. Compared with the open approach, the laparoscopic-assisted approach is associated with less blood loss and earlier return of bowel function.

A novel miR‐203‐DNMT3b‐ABCG2 regulatory pathway predisposing colorectal cancer development

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. The majority of studies to date focused on genetic mutations and epigenetic changes that drive the CRC carcinogenesis process. Xenobiotic transporters play an important role in safeguarding our body from external toxic substances. These transporters lining the gastrointestinal tract protect us from dietary carcinogens. This study aimed to investigate the downregulation of an efflux transporter ABCG2 in CRC versus normal colon mucosa, so as to shed light on its relevance to CRC initiation and progression. We found that ABCG2 expression is at least 50‐fold lower in adenomatous polyps and colon carcinoma specimens obtained from CRC patients than in their matched pair of adjacent normal colon mucosa. The underlying mechanism(s) for ABCG2 under‐expression in CRC is currently not known. To this end, aberrant promoter methylation of ABCG2 has been reported to cause its repression in a few cancer types including renal carcinoma and multiple myeloma. In this study, miR‐203 was found to be downregulated in all polyps and CRC specimens, relative to adjacent normal colon mucosa. We demonstrated that the de novo DNA methyltransferase DNMT3b is a direct target of miR‐203. Importantly, by relieving the repression on DNMT3b, the lower expression of miR‐203 in CRC caused ABCG2 promoter methylation and remarkable lower ABCG2 expression in colon cancer cell lines and the patient CRC specimens. The restoration of ABCG2 function via modulating this new microRNA‐methylation mechanism in precancerous cells may represent an attractive strategy to delay the carcinogenesis process.

Su1784 The Impact of Fast-Track Versus Traditional Perioperative Program on the Clinical and Immunological Outcomes After Laparoscopic Colorectal Surgery: A Prospective Randomized Trial

Introduction: Financial implications on regionalization of healthcare and programmatic development are not often considered. We undertook this study to evaluate and compare hospital cost of care and income with a common operation (laparoscopic cholecystectomy) versus an operation often associated with HPB programmatic development and healthcare regionalization (pancreaticoduodenectomy). Methods and Procedures: The charges and reimbursements of all laparoscopic cholecystectomies (n=201) and pancreaticoduodenectomies (n=44) at one hospital undertaken from June 2012 to June 2013 were determined. Comparisons were undertaken using ANOVA with significance accepted at p ≤ 0.05. Data are reported as median data or as median (mean ± SD). Results: Pancreaticoduodenectomy, relative to laparoscopic cholecystectomy, had greater time in the operating room (283 min vs. 93 min), hospital charges (

Abstract 791: The predictive value of a novel miR-519c-HuR-ABCG2 regulatory pathway in chemoresistance of colorectal cancer

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Compromised Tissue Renewal in the Ageing Human Colonic Epithelium

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Laparoscopic-Assisted Versus Open Abdominoperineal Resection for Low Rectal Cancer: A Prospective Randomized Trial

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