Oswens Siu-Hung Lo

Impact of laparoscopic colorectal resection on surgical site infection.

Objectives:This study aimed to identify the risk factors of surgical site infection (SSI) in elective colorectal resection and the strategy for prevention of SSI in modern era of colorectal surgery. Background:The practice of colorectal surgery has undergone remarkable evolution recently because of application of laparoscopic resection. This could affect SSI in colorectal patients. An updated investigation of SSI under current practice of colorectal surgery would provide valuable information. Methods:This was a prospective study of SSI on 1011 patients, who had elective colorectal resection in a university teaching hospital, during January 2002 to December 2006. Standard definition and postoperation follow-up of SSI were adopted through collaboration between surgeons and wound surveillance program of Infection Control Unit. Risk factors of SSI were evaluated. Logistic regression was used to perform multivariate analysis and decide independent risk factors of SSI. Results:The overall rate of incisional SSI and organ/space SSI was 4.8% and 1.7%, respectively. Rate of incisional SSI in open and laparoscopic colorectal resection was 5.7% and 2.7%, respectively. Anastomotic leakage was the only factor that predicted organ/space SSI (P < 0.01). Independent risk factors of incisional SSI included blood transfusion [P = 0.047; odds ratio (OR) = 2.43; 95% confidence interval (CI): 1.0–5.9], anastomotic leakage (P < 0.01; OR = 6.5; 95% CI: 2.3–18.6), and open colorectal resection (P = 0.037; OR = 2.36; 95% CI: 1.1–5.3). Conclusion:In current practice of colorectal surgery, operative factors are more important than patient factors for SSI. Good surgical technique to reduce anastomotic leakage and reduce blood transfusion has paramount importance in SSI prevention. Laparoscopic surgery was associated with reduction of rate of SSI by more than 50% when compared with open surgery and would have a strong impact on the prevention of surgical infection.

Detection of Colorectal Adenoma by Narrow Band Imaging (HQ190) vs. High-Definition White Light Colonoscopy: A Randomized Controlled Trial

OBJECTIVES:The benefits of narrow band imaging (NBI) on enhancing colorectal adenoma detection remain questionable. We tested whether the new generation of NBI (190-NBI), which is twice as bright as the previous version, would improve adenoma detection when compared with high-definition white light (HD-WL) colonoscopy.METHODS:It was a randomized controlled trial with tandem colonoscopy. We recruited patients who underwent colonoscopy for symptoms, screening, or surveillance. Patients were randomized for the use of either 190-NBI or HD-WL on withdrawal. Tandem colonoscopy was performed by using the same assigned colonoscope and withdrawal method. Lesions detected on first-pass and second-pass examination were used for adenoma detection and miss rates, respectively. The primary outcomes were adenoma and polyp detection rates.RESULTS:A total of 360 patients were randomized to undergo either 190-NBI or HD-WL colonoscopy. Both the adenoma and polyp detection rates were significantly higher in the 190-NBI group compared with the HD-WL group (adenoma: 48.3% vs. 34.4%, P=0.01; polyps: 61.1% vs. 48.3%, P=0.02). The mean number of polyps detected per patient was higher in the 190-NBI group (1.49% vs. 1.13, P=0.07). There was no significant difference in the adenoma miss rates between the two groups (21.8% vs. 21.2%). Multivariate analysis showed that the use of 190-NBI (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.10–3.12), withdrawal time (OR 1.29; CI 1.19–1.38), patients age (OR 1.04; CI 1.01–1.06), and male gender (OR 2.38; CI 1.42–3.99) were associated with adenoma detection.CONCLUSIONS:190-NBI colonoscopy was superior to the conventional HD-WL in detecting colorectal adenomas or polyps, but there was no significant difference in adenoma miss rates.

Prognostic Significance of CD26 in Patients with Colorectal Cancer

Background CD26, dipeptidyl peptidase IV, was discovered firstly as a membrane-associated peptidase on the surface of leukocyte. We previously demonstrated that a subpopulation of CD26+ cells were associated with the development of distant metastasis, enhanced invasiveness and chemoresistance in colorectal cancer (CRC). In order to understand the clinical impact of CD26, the expression was investigated in CRC patients specimens. This study investigated the prognostic significance of tumour CD26 expression in patients with CRC. Examination of CD26+ cells has significant clinical impact for the prediction of distant metastasis development in colorectal cancer, and could be used as a selection criterion for further therapy. Methods Tumour CD26 expression levels were studied by immunohistochemistry using Formalin-fixed paraffin embedded (FFPE) tissues in 143 patients with CRC. Tumour CD26 expression levels were correlated with clinicopathological features of the CRC patients. The prognostic significance of tumour tissue CD26 expression levels was assessed by univariate and multivariate analyses. Result CD26 expression levels in CRC patients with distant metastasis were significantly higher than those in non-metastatic. High expression levels of CD26 were significantly associated with advanced tumour staging. Patients with a high CD26 expression level had significantly worse overall survival than those with a lower level (p<0.001). Conclusions The expression of CD26 was positively associated with clinicopathological correlation such as TNM staging, degree of differentiation and development of metastasis. A high CD26 expression level is a predictor of poor outcome after resection of CRC. CD26 may be a useful prognostic marker in patients with CRC.

Post-Operative Plasma Osteopontin Predicts Distant Metastasis in Human Colorectal Cancer

Background The overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients. Methods This randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay. Results Our findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration. Conclusions The results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients.

Osteopontin Overexpression Induced Tumor Progression and Chemoresistance to Oxaliplatin through Induction of Stem-Like Properties in Human Colorectal Cancer

Colorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. The poor prognosis of colorectal cancer patients is due to development of chemoresistance and cancer metastasis. Recently osteopontin (OPN) has been associated with stem-like properties in colorectal cancer. This study further examined the clinicopathological significance of OPN in CRC and its effect on chemoresistance and transcription of stem cell markers. We examined the transcription level of OPN in 84 CRC patients and correlated the expression with their clinicopathological parameters. The associations of OPN overexpression with transcription of stem cell markers and response to chemotherapy in DLD1-OPN overexpressing clones and CRC patients were also investigated. Our results showed that OPN was significantly overexpressed in CRC, and its overexpression correlated with tumor stage and poor prognosis. Overexpression of CRC induced OCT4 and SOX2 expression in vitro and correlated with SOX2 overexpression in CRC patients. In addition, DLD1-OPN overexpressing cells showed enhanced ability to survive upon oxaliplatin treatment, and OPN expression was higher in CRC patients who were resistant to oxaliplatin-involved chemotherapy treatment. Thus, CRC cells overexpressing OPN demonstrated stem-like properties and OPN inhibition is a potential therapeutic approach to combat CRC progression and chemoresistance.

Colorectal resection after stent insertion for obstructing cancer: comparison between open and laparoscopic approaches

Aim: To evaluate surgical outcomes after stent insertion for obstructing colorectal malignancy and to compare between laparoscopic and open approach. Methods: Surgical resection was performed after stent insertion for malignant colorectal obstruction in 36 patients with a median age of 73 years. Eighteen patients were treated with open resection, whereas 18 underwent a laparoscopic resection. The outcomes were evaluated and comparison was made between patients with laparoscopic and open resection. Results: The mean interval between stent insertion and surgery was 11 days. One patient died within 30 days (2.8%). The overall incidence of postoperative morbidity was 22% and reoperation was required in 3 patients (8.8%). The median postoperative hospital stay was 8.5 days for the open surgery group and 5.5 days for the laparoscopic group (P=0.004). The postoperative morbidity rates for the open and laparoscopic groups were 33.3% and 11.1%, respectively (P=0.228). In those patients with nonmetastatic disease, with the median follow-up of 20 months, the 5-year survival rate was 49.5%. Conclusions: Our experience showed that after successful endoscopic stent insertion for malignant colorectal obstruction, elective surgical resection could be performed safely. The combined endoscopic and laparoscopic procedure provides a less invasive alternative to the multistage open operations and is feasible for patients with obstructing colon cancer.

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.

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 patients clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearsons 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.

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

Colorectal cancer is the third most common cancer in the world and liver is the most frequent site of distant metastasis with poor prognosis. The aim of this study is to investigate microRNAs leading to liver metastasis. We applied microarray analysis and quantitative PCR to identify and validate dysregulated miRNAs in liver metastases when compared to primary CRCs. Functional significance and the underlying molecular mechanism of selected miRNA was demonstrated by a series of in vitro and in vivo assays. Our microarray analysis and subsequent quantitative PCR validation revealed that miR-885-5p was strongly up-regulated in liver metastases and in CRC cell-lines derived from distant metastases. Overexpression of miR-885-5p significantly induced cell migration, cell invasion, formation of stress fibre in vitro and development of liver and lung metastases in vivo. MiR-885-5p induced metastatic potential of CRC by repressing cytoplasmic polyadenylation element binding protein 2 transcription through directly binding to two binding sites on its 3′ untranslated region, and consequently led to up-regulation of TWIST1 and hence epithelial-mesenchymal transition. Our findings demonstrated the overexpression of miR-885-5p in liver metastasis and its roles in inducing CRC metastasis, potentiating development of miR-885-5p inhibitor to treat advanced CRC in the future.

Needlescopic Totally Extraperitoneal Hernioplasty for Unilateral Inguinal Hernia in Adult Patients

OBJECTIVE Totally extraperitoneal (TEP) inguinal hernioplasty for inguinal hernia is associated with less postoperative pain, shorter hospital stays, less chronic pain, and increased patient satisfaction when compared with the open Lichtenstein approach‥ However, only few studies to date have compared conventional with needlescopic TEP hernioplasty for treating unilateral inguinal hernias in adult patients. We report our prospective study that compared the postoperative outcomes of these two approaches over a 2-year period. METHODS From July 2007 to June 2009, a total of 32 patients underwent attempted unilateral needlescopic TEP hernioplasty. All data were prospectively collected and analysed, including demographic features, types of hernia, and postoperative outcome. The results were compared with those of an agematched cohort of 32 patients who underwent conventional TEP hernioplasty in the same period. RESULTS Needlescopic TEP hernioplasty was successfully performed in 24 patients. The other eight procedures were completed with conventional TEP approaches after changing one or two 5-mm ports. The most common hernia type was Nyhus type III (38/64, 59.3%). There was no significant difference in the mean operative time, hospital stay, and postoperative pain scores between the needlescopic and conventional approaches. There was no major complication detected on the first visit, except seroma formation (9 patients in the needlescopic group and 11 in the conventional group), all of which was resolved with conservative management. No recurrence of hernia was noted in either group during the mean follow-up period of 88.0 weeks. CONCLUSION Needlescopic TEP hernioplasty was a feasible technique in selected patients for inguinal hernia repair. Postoperative recovery following both approaches was similar. However, because this was a small cohort study, larger prospective, randomized controlled trials are required to establish the longterm benefit, safety and complications of needlescopic surgery.