Needs assessment study of postgraduate surgical education in Sudan: Trainees perspective.

INTRODUCTION: Global interest has increased in improving the quality and increasing the number of graduates from surgical training programmes in countries with limited resources. Needs assessment of stakeholders in the training programmes represent the backbone of such process. The aim of this study was to assess the surgical training in Sudan from trainees' perspective in order to inform training delivery. METHODS: We adopted mixed methods design using focus group discussion for qualitative data collection and questionnaire survey for quantitative data. NVivo 20 Pro was used to organize qualitative data and SPSS 24.0 was used for quantitative data analysis. RESULTS: Thematic analysis of qualitative data identified three themes. Trainees were overall satisfied that they will make good surgeons after completion of the programme. They identified case volume and collaborations with colleagues as the main strengths of the programme and lacking clear objectives for each year of training and academic activities as the main weaknesses. They suggested motivation of trainers and utilization of online resources and meeting platforms as solutions to improve supervision and academic activities during training. CONCLUSION: The gaps in training and their suggested solutions highlighted by trainees in this study should form the base for reforming the surgical training in Sudan and countries with similar circumstances.

Peri-procedural thromboprophylaxis in the prevention of DVT in varicose vein interventions: A systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was performed to determine the role of thromboprophylaxis in the prevention of venous thromboembolism in patients undergoing varicose vein interventions. METHODS: PUBMED, EMBASE and Web of Science were searched for comparative studies of patients undergoing varicose vein interventions and received either thromboprophylaxis or no thromboprophylaxis. Data were collected on the number of thrombotic events including deep vein thrombosis (DVT), pulmonary embolism (PE) and endothermal heat-induced thrombosis (EHIT) as well as bleeding events. The primary outcomes for the meta-analysis were the risk of all thrombotic events, risk of DVT and risk of bleeding. Pooled risk ratios were calculated using random effects modelling. RESULTS: Eight studies (6479 participants) were included. The use of thromboprophylaxis reduces the risk of all thrombotic events (Pooled risk ratio = 0.63, 95% Confidence interval [CI], 0.04-10.43) and the risk of DVT (Pooled risk ratio = 0.59, 95% CI, 0.08-4.60) with no increased risk of bleeding (Pooled risk ratio = 0.66, 95% CI, 0.06-7.21]. Rivaroxaban has similar efficacy in the prevention of DVT compared to Fondaparinux in patients undergoing endovenous ablation of varicose veins (Pooled risk ratio = 0.68, 95% CI, 0.06-7.41). An extended course of thromboprophylaxis reduces the risk of developing DVT compared to a short course (Pooled risk ratio = 1.40, 95% CI, 0.44-4.46). However, the two studies reporting on the duration of thromboprophylaxis did not stratify patients according to their risk of developing venous thromboembolism. CONCLUSION: The use of thromboprophylaxis in patients undergoing varicose vein interventions reduces the risk of venous thromboembolism with no significant increase in the risk of bleeding. However, the included studies were underpowered with high to moderate risk of bias. Therefore, more randomised controlled trials with a large sample size are needed in order to provide high quality evidence for clinical practice.

Does metformin improve reproduction outcomes for non-obese, infertile women with polycystic ovary syndrome? Meta-analysis and systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 10-12% of women of reproductive age. The prevalence of infertility in women with PCOS is high at between 70 and 80%. Treatment initially includes recommendations to follow preconception guidelines, such as lifestyle changes, folic acid therapy and halting the consumption of tobacco and alcohol. Management with pharmacological agents and surgical procedures have been incorporated into treatment regimens to improve fertility. Of these, metformin, an insulin sensitizer used as oral hypoglycemic agent, is gaining popularity. OBJECTIVES: The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the role of metformin in improving the reproduction outcomes for non-obese, infertile women with polycystic ovary syndrome. SEARCH METHODS: In June 2019, we searched PubMed (from inception to present), Ovid Medline, Ovid EMBASE, Scopus, and the Cochrane library without date or language restrictions for relevant RCTs. Search was then updated in April 2020. Bibliographies of included studies were also searched for eligible studies. SELECTION CRITERIA: RCTs that compared the effectiveness of metformin with other modalities in treating infertility in non-obese women with PCOS were included. The eligible outcomes for inclusion were pregnancy rate, miscarriage rate, live birth rate, ovarian hyperstimulation (OHSS) and multiple pregnancy. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers, and any disagreements resolved by consensus or by arbitration by a third reviewer. Where two or more studies reported on the same outcome a meta-analysis was conducted using Cochrane RevMan 5. RESULTS: We found 21 RCTs which were eligible for inclusion in our systematic review, including 2638 patients with PCOS. Our meta-analysis showed that the use of metformin in non-obese women with PCOS is associated with slight increase in clinical pregnancy rate compared to placebo (47.7% vs. 42.9%) (Pooled risk ratio = 1.08 [0.82, 1.42], 95% CI, p = 0.60). It also showed that metformin is comparable to clomiphene citrate (CC) when the outcome is clinical pregnancy rate and the risk of multiple pregnancies tended to be lower (Pooled risk ratio = 0.36 [0.07, 1.92], 95% CI, p = 0.23, 3 studies). However, metformin had a higher risk of miscarriage rate (Pooled risk ratio = 2.41 [0.39, 14.86], 95% CI, p = 0.72). Furthermore, this analysis suggested that adding metformin to CC treatment decreases miscarriage risk by two folds compared to metformin alone (Pooled risk ratio = 2.67 [1.32, 5.39], 95% CI, p = 0.006) and showed no difference compared to CC alone. In comparison to letrozole, combination of metformin and CC is associated with lower clinical pregnancy rate (Pooled risk ratio = 0.52 [0.14, 1.91] 95% CI, p = 0.33) and multiple pregnancies (Pooled risk ratio = 0.45 [0.06, 3.19] 95% CI, p = 0.42). CONCLUSION: Although this study illustrated that metformin may be better than placebo for some pregnancy outcomes, stronger, more definitive evidence from sufficiently powered trials are required before considering metformin for treating non-obese infertile women with PCOS within the current recommended guidelines.

Systematic review and meta-analysis of randomized controlled trials evaluating long-term outcomes of endovenous management of lower extremity varicose veins.

BACKGROUND: Early studies have demonstrated that endovenous therapy for varicose veins is associated with a faster recovery and lower complication rates compared with conventional therapy. More than one million procedures have been performed worldwide. The objective of this study was to determine long-term efficacy of currently available endovenous therapy methods for varicose veins compared with conventional surgery (saphenofemoral ligation and stripping of great saphenous vein [GSV] with or without multiple avulsions) in management of GSV-related varicose veins. METHODS: In July 2017, we searched MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Scopus, Cochrane Library, and Web of Science without date or language restriction for relevant randomized controlled trials (RCTs). Bibliographies of included studies were also searched for additional studies. RCTs comparing conventional surgery and endovenous therapy for treating lower extremity varicose veins with 5 years or more of follow-up were selected. Data extraction and quality assessment were performed independently by two review authors, and any disagreements were resolved by consensus or by arbitration of a third author. Cochrane RevMan 5 was used for analysis. RESULTS: At time of data extraction, long-term follow-up was available for endovenous laser therapy (EVLT), radiofrequency ablation (RFA), and ultrasound-guided foam sclerotherapy. Included in the review were nine RCTs. The RCTs included 2185 legs; however, only 1352 legs were followed up for 5 years (61.9%). There was no statically significant difference in recurrence rate in comparing EVLT with conventional surgery in treating GSV incompetence (36.6% vs 33.3%, respectively; pooled risk ratio, 1.35; 95% confidence interval, 0.76-2.37; P = .3). Also, no significant difference was determined for recurrence rate in comparing RFA with surgery or EVLT. CONCLUSIONS: Although the analysis showed that EVLT and RFA are as effective as conventional surgery in treating saphenous venous insufficiency, the number of patients available for analysis was too small for definitive conclusions to be drawn.

Supervised exercise therapy in the management of peripheral arterial disease - an assessment of compliance.

BACKGROUND: Supervised exercise therapy (SET) is an effective option in the management of peripheral arterial disease (PAD). Unfortunately, poor compliance remains prevalent. This study aimed to assess patient exercise compliance and to identify factors influencing symptomatic improvement and SET participation. PATIENTS AND METHODS: Data regarding attendance at SET for this cohort study were extracted from a prospectively maintained database of patients with claudication attending SET at Dublin City University. All patients had ankle brachial index confirmed PAD with associated intermittent claudication. Exercise performance and symptomatic data were gathered retrospectively using patient charts and interviews. RESULTS: Ninety-eight patients were referred for SET during the study period. The mean age was 69.2 (± 10.1) with 18 % being female. Median follow-up was 25.1 months (IQ range 17.0-31.6). Overall, the mean number of sessions attended per patient was 19.5. Exercise compliance was associated with a significant improvement in symptoms (p = 0.001). Other factors including anatomical level of claudication (P = 0.042) and educational level (p = 0.007) were found to affect the outcome of SET. Multivariate analysis revealed hypertension as a predictor of symptomatic outcome after SET (p = 0.045). Furthermore, ex-smokers (p = 0.021) and those previously diagnosed with hypercholesterolaemia (p = 0.020) or ischaemic heart disease (p = 0.029) had superior exercise compliance. Using linear regression, smoking history (p = 0.024) was identified as a predictor of compliance to SET. CONCLUSIONS: Establishing exercise compliance remains challenging in the PAD cohort. Pre-exercise patient education and personalised exercise prescriptions may result in improvements in function and compliance.

Can a Neutrophil-Lymphocyte Ratio Derived from Preoperative Blood Tests Predict Arteriovenous Fistula Maturation?

BACKGROUND: To evaluate the association between inflammatory markers expressed as neutrophil-lymphocyte ratio (NLR) and process of arteriovenous fistula (AVF) maturation. METHODS: A retrospective review of patients with end-stage renal disease referred for formation of a new AVF in one center. Patients referred to the vascular service in the University Hospital of Limerick for creation of vascular access between 2009 and 2013. The association between NLR, calculated from preoperative blood tests, and functional fistula maturation, as determined by successful use of the AVF for 6 consecutive hemodialysis sessions, was investigated using univariate and logistic regression analyses. A logistic regression analysis was carried out to assess potential influence from other factors related to AVF maturation. Stepwise regression test was performed including the NLR. RESULTS: Overall AVF functional maturation rate in our study was 53.7% (66/123). Patients with matured AVFs had an NLR of 4.850 (1.8-15.7) compared with 3.554 (1.7-15.0); this difference was found to be significant (P = 0.024). Female gender (P = 0.008) and a history of kidney transplant (P = 0.004) were the only independent factors of fistula maturation outcome in a logistic regression model. CONCLUSION: Increased level of NLR was found to be associated with fistula maturation; however, more studies are needed to validate this finding.

Evidence for varicose vein surgery in venous leg ulceration.

BACKGROUND: Venous leg ulcers affect 1-3% of adults with a significant economic impact, utilizing 1% of annual healthcare budgets in some western European countries. OBJECTIVES: To determine the effects of intervention for incompetent superficial veins on ulcer healing and recurrence in patients with active or healed venous ulcers. SEARCH METHODS: In October 2014, we searched Medline, CINAHL, EMBASE, Scopus, the Cochrane library and Web of Science without date or language restriction for relevant randomized or observational studies. Bibliographies of included studies were also searched for additional studies. SELECTION CRITERIA: Observational studies or randomized controlled trials comparing intervention for varicose veins with compression therapy alone for venous leg ulcers were eligible. In addition, studies compared open to endovenous therapy for varicose veins in patients with leg ulcers and those compared treating saphenous and perforating veins to treating saphenous veins only were also included. Studies had to report at least one ulcer-related outcome (healing rate, recurrence or time to healing). DATA COLLECTION AND ANALYSIS: Details of potentially eligible studies were extracted and summarized using a data extraction table. Data extraction and quality assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third author. RESULTS: Intervention for superficial venous reflux improved ulcer healing (risk ratio = 1.11 [1.00, 1.22], 95% CI, p = 0.04) and reduced recurrence (risk ratio = 0.48 [0.32, 0.67], 95% CI, p < 0.0001) compared to compression alone, with low level of evidence. CONCLUSION: This review confirmed that the evidence for a beneficial effect of endovenous and open surgery for varicose vein in venous leg ulcer is at beast weak. A well-structured RCT is required to investigate the role of endovenous ablation of incompetent superficial veins in improving venous leg ulcer outcomes.

Arteriovenous fistula in dialysis patients: Factors implicated in early and late AVF maturation failure.

Increasing numbers of patients are being diagnosed with end-stage renal disease (ESRD), and the demand for on haemodialysis (HD) is rising. Arteriovenous fistulae (AVFs) remain the best conduit for adequate HD, with fewer complications associated with long-term use compared to bypass grafts and central venous catheters. However, it is known that many newly formed fistulae do not mature to provide useful HD access. The paper provides a narrative overview of factors influencing the process of AVF maturation failure.

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

BACKGROUND: Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. METHODS/DESIGN: Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). DISCUSSION: RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.

Role of far infra-red therapy in dialysis arterio-venous fistula maturation and survival: systematic review and meta-analysis.

INTRODUCTION: A well-functioning arteriovenous fistula (AVF) is the best modality for vascular access in patients with end-stage renal disease (ESRD) requiring haemodialysis (HD). However, AVFs' main disadvantage is the high rate of maturation failure, with approximately one third (20%-50%) not maturing into useful access. This review examine the use of Far-Infra Red therapy in an attempt to enhance both primary (unassisted) and secondary (assisted) patency rates for AVF in dialysis and pre-dialysis patients. METHOD: We performed an online search for observational studies and randomised controlled trials (RCTs) that evaluated FIR in patients with AVF. Eligible studies compared FIR with control treatment and reported at least one outcome measure relating to access survival. Primary patency and secondary patency rates were the main outcomes of interest. RESULTS: Four RCTs (666 patients) were included. Unassisted patency assessed in 610 patients, and was significantly better among those who received FIR (228/311) compared to (185/299) controls (pooled risk ratio of 1.23 [1.12-1.35], p = 0.00001). In addition, the two studies which reported secondary patency rates showed significant difference in favour of FIR therapy--160/168 patients--compared to 140/163 controls (pooled risk ratio of 1.11 [1.04-1.19], p = 0.003). CONCLUSION: FIR therapy may positively influence the complex process of AVF maturation improving both primary and secondary patency rates. However blinded RCTs performed by investigators with no commercial ties to FIR therapy technologies are needed.

Mismatch repair protein expression in colorectal cancer.

INTRODUCTION: Alterations in at least six of the genes that encode proteins involved in the mismatch repair (MMR) system have been identified in either HNPCC or sporadic colon cancer. We aimed to analyse the proportion of patients with colorectal cancer with loss of immunostaining for MMR proteins in order to determine the feasibility of molecular screening for the loss of MMR proteins through the study of unselected patients with colorectal cancer. METHODS: A group of 33 patients with colorectal cancer was randomly selected from the department of surgery bio-bank to determine the expression of MMR proteins in their FFPE tumour tissues using immunohistochemistry techniques. Changes in protein expression following transfection of colorectal tissues were observed in stained cells using Olympus BX60 microscope and image analySIS software. RESULTS: Of the tissue specimens in which acceptable immunostaining was achieved, three samples showed loss of one or more of the MMR proteins. Both hMLH1 and hPMS2 proteins were not expressed in a 36 years old woman with cancer of the caecum. The expression of hMSH6 protein was undetermined in tumour tissues retrieved from a 61 years old man with cancer of the proximal colon. The third case was a 77 years old man with no documented family history of cancer, who had carcinoma of the rectum. He showed loss of hMLH1 expression in the tumour tissues. CONCLUSIONS: Our findings and the previous reports pointed out the importance of molecular screening of patients with colorectal cancer for MSI using immunohistochemistry. This strategy managed to identify mutations in patients otherwise would not have been detected.

Clinical applications of gene expression in colorectal cancer.

BACKGROUND: Despite developments in diagnosis and treatment, 20% of colorectal cancer (CRC) patients present with metastatic disease and 30% of cases recur after curative surgery. Furthermore, the molecular factors involved in prognosis and response to therapy in CRC is poorly understood. The aims of this study were to quantitatively examine the expression of target genes in colorectal cancer and to correlate their expression levels with clinico-pathological variables. METHODS: A detailed analysis of published CRC microarray data was performed to identify the most prominent genes. The selected genes were validated in fifty-two pairs of fresh colorectal tumour and associated normal tissue specimens by RQ-PCR using TaqMan(®) assays. Statistical analysis and correlation with clinicopathological data was performed using SPSS software. RESULTS: Expression levels of CXCL12 (P=0.000), CDH17 (P=0.026), MUC2 (P=0.000), L-FABP (P=0.000) and PDCD4 (P=0.000) were down regulated and IL8 (P=0.000) was upregulated in tumours compared to normal colorectal tissues. No significant differences were noted in expression of CEACAM5, CXCR4, CXCR7, TGFB1, TGFBR1 and TGFBR2. Furthermore, we found significant associations of gene expression levels and clinicopathological variables such as tumour size, grade, invasion and lymph node status. CONCLUSIONS: We identified a comprehensive list of genes with highly differential expression patterns in colorectal cancer that could serve as molecular markers to complement existing histopathological factors in diagnosis, follow up and therapeutic strategies for individualised care of patients.

miRNA expressions in rectal cancer as predictors of response to neoadjuvant chemoradiation therapy.

INTRODUCTION: Neoadjuvant chemoradiation therapy has been shown to improve the outcome in patients with rectal cancer and is generally accepted as standard care; however, only selected patients would benefit from this treatment. We aimed to identify predictors of response to neoadjuvant chemoradiation therapy in colorectal cancer using formalin-fixed paraffin-embedded (FFPE) tissues as source of genetic materials and microarray analysis as investigation tool. METHODS: After optimization of RNA extraction methods from FFPE, microarray analysis was carried out on total RNA extracted from 12 pre-treatment FFPE rectal tissues using Megaplex pool A. Microarray data were analysed using an artificial neural network algorithm. Statistical analysis and correlation with clinicopathological data was performed using SPSS software. RESULTS: A distinct miRNA expression signature predictive of response to neoadjuvant CRT in 12 FFPE pre-treatment rectal cancer tissue samples was identified. These signatures consisted of three miRNA transcripts (miR-16, miR-590-5p and miR-153) to predict complete vs. incomplete response and two miRNA transcript (miR-519c-3p and miR-561) to predict good vs. poor response with a median accuracy of 100 %. CONCLUSION: Using microarray analysis of pretreatment FFPE rectal cancer tissues, we identified for the first time a group of miRNA predictors of response to neoadjuvant CRT. This, indeed, can lead to a significant improvement in patient selection criteria and personalized rectal cancer management.

A comparative study of the bell-bottom technique vs hypogastric exclusion for the treatment of aneurysmal extension to the iliac bifurcation.

INTRODUCTION: A significant proportion of patients undergoing endovascular aneurysm repair (EVAR) have common iliac artery aneurysms (CIAA). Aneurysmal involvement at the iliac bifurcation potentially undermines long-term durability. METHODS: Patients with CIAA who underwent EVAR were identified in two teaching hospitals. Bell-bottom technique (BBT; iliac limb ≥20 mm) or internal iliac artery embolization and limb extension to the external iliac artery (IIE + EE) were used. Outcome between these two approaches was compared. RESULTS: We identified 185 patients. Indication for EVAR included asymptomatic abdominal aortic aneurysm (AAA) in 157, symptomatic or ruptured aneurysm in 19, and CIAA in nine. Mean AAA diameter was 59 mm. Among 260 large CIAAs that were treated, BBT was used to treat 166 CIAA limbs, and 94 limbs underwent IIE + EE. Total reintervention rates were 11% for BBT (n = 19) and 19.1% for IIE + EE (n = 18; P = .149). Rates of reintervention for type Ib or III endoleak were 4% for BBT (n = 7) and 4% for IIE + EE (n = 4; P > .99). The difference in limb patency rates was not significant. The 30-day mortality rate was 1%. Median follow-up was 22 months. Complications did not differ significantly between the two groups; however, the combined incidence of perioperative complications and reinterventions was higher in the IIE + EE group (49% vs 22%; P = .002). CONCLUSIONS: The combined incidence of perioperative complications and reinterventions is significantly higher with IIE + EE than with BBT; therefore, when feasible, BBT is desirable.

MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease.

PURPOSE: Colorectal cancer (CRC) is a clinically diverse disease whose molecular etiology remains poorly understood. The purpose of this study was to identify miRNA expression patterns predictive of CRC tumor status and to investigate associations between microRNA (miRNA) expression and clinicopathological parameters. METHODS: Expression profiling of 380 miRNAs was performed on 20 paired stage II tumor and normal tissues. Artificial neural network (ANN) analysis was applied to identify miRNAs predictive of tumor status. The validation of specific miRNAs was performed on 102 tissue specimens of varying stages. RESULTS: Thirty-three miRNAs were identified as differentially expressed in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p, miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease. Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced expression of miR-143 (p = 0.016) were associated with aggressive mucinous phenotype. Increased expression of miR-10b was also associated with mucinous tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b expression were observed from T1 to T4 lesions and from stage I to IV disease. CONCLUSION: Association of specific miRNAs with clinicopathological features indicates their biological relevance and highlights the power of ANN to reliably predict clinically relevant miRNA biomarkers, which it is hoped will better stratify patients to guide adjuvant therapy.

Bilateral breast cancer: analysis of incidence, outcome, survival and disease characteristics.

There has been conflicting evidence on the impact of bilateral breast cancer (BBC) on the survival and management of patients. The objectives of this study were to address the incidence of BBC and to investigate its characteristics and outcome compared to unilateral cancer. Data were acquired from the prospectively maintained NUIG breast cancer database between 1988 and 2008. BBC were then categorized as synchronous (within 12 months) or metachronous (after 12 months of first tumour). SPSS was used for data analysis. The incidence of BBC in our population was 4.4% (112 of 2,524). Of those 2.1% were synchronous while 2.3% were metachronous. Compared to unilateral cases, bilateral cancer patients were younger (P = 0.021) and had smaller size (P = 0.001) and earlier stage (P < 0.001) tumours at diagnosis. We identified the HER2/neu positivity as a risk factor for developing contralateral breast tumour and ER negativity as a risk factor for developing metachronous tumours. While there was no significant difference in survival for patients with bilateral compared to unilateral tumour (P > 0.05), the synchronous tumour was associated with poorer survival (P = 0.010) in comparison to metachronous tumour. This large single-institutional experience does not support the increasing practice of prophylactic mastectomy but does justify regular follow-up with mammography for early detection of contralateral tumour.

Identification of endogenous control genes for normalisation of real-time quantitative PCR data in colorectal cancer.

BACKGROUND: Gene expression analysis has many applications in cancer diagnosis, prognosis and therapeutic care. Relative quantification is the most widely adopted approach whereby quantification of gene expression is normalised relative to an endogenously expressed control (EC) gene. Central to the reliable determination of gene expression is the choice of control gene. The purpose of this study was to evaluate a panel of candidate EC genes from which to identify the most stably expressed gene(s) to normalise RQ-PCR data derived from primary colorectal cancer tissue. RESULTS: The expression of thirteen candidate EC genes: B2M, HPRT, GAPDH, ACTB, PPIA, HCRT, SLC25A23, DTX3, APOC4, RTDR1, KRTAP12-3, CHRNB4 and MRPL19 were analysed in a cohort of 64 colorectal tumours and tumour associated normal specimens. CXCL12, FABP1, MUC2 and PDCD4 genes were chosen as target genes against which a comparison of the effect of each EC gene on gene expression could be determined. Data analysis using descriptive statistics, geNorm, NormFinder and qBasePlus indicated significant difference in variances between candidate EC genes. We determined that two genes were required for optimal normalisation and identified B2M and PPIA as the most stably expressed and reliable EC genes. CONCLUSION: This study identified that the combination of two EC genes (B2M and PPIA) more accurately normalised RQ-PCR data in colorectal tissue. Although these control genes might not be optimal for use in other cancer studies, the approach described herein could serve as a template for the identification of valid ECs in other cancer types.