(AMCO) and are increasingly used either palliatively or as a bridge to surgery (BTS) in patients in whom a definitive surgical approach is unsuitable. We evaluated short-term outcomes of malignant colorectal obstructive patients treated with SEMS in our institution over a 3-year period. Methods A prospectively maintained database was reviewed to identify all patients who presented to our institution with AMCO between August 2010 and 2013 and who were treated with a SEMS either temporarily or permanently. Additional data was retrieved from chart and pathology reviews. A single colorectal surgeon inserted all stents under both endoscopic and fluoroscopic guidance. Data was analysed using SPSSv21 (SPSS Inc., Chicago, IL, USA) and presented as median (interquartile range). Continuous variables were assessed using analysis of variance. A p value <0.05 was considered statistically significant. Results Sixteen patients each had a single stent inserted during the study period, either palliatively (n = 11) or as a BTS (n = 5). Their median (IQR) age was 75 (21) years and 12 (75%) patients were males. Most tumours were located in the sigmoid colon (6/16, 37%). The technical and clinical success rates were both 87.5% (14/16) and there were no SEMS-related perforations. The two unsuccessful stenting cases both had metastatic disease and required emergency surgery while five patients with potentially curable disease proceeded to elective resections. There was no procedure-related mortality. There was no difference in the median length of stay (LOS) post SEMS insertion in the palliative group compared to the BTS group [4 (4) vs. 5 (3), p = 0.2]. However, the median (IQR) LOS post acute surgery was longer than elective surgery [45 (30) vs. 14 (8) days, p = 0.018]. All patients in the BTS group were stoma-free post-operatively, while both patients who had emergency surgery ended up with permanent stomas. Finally, the stent complication rate was 6.2% (1/16), secondary to migration in a patient who was stented palliatively. The latter patient did not undergo further attempted stenting as his obstructive symptoms had been alleviated. Conclusion AMCO poses significant challenges in management due to the frailty of the presenting patients and the high morbidity/mortality rates associated with emergency surgery. Although limited by a small sample size, our study shows that SEMS are a favourable alternative to emergency surgery for the management of AMCO. Further larger scale studies looking at long-term survival and oncological outcomes are awaited. Disclosure of Interest None Declared. Introduction Colorectal cancer (CRC) is the fourth most common cancer in the UK and was responsible for more than 15,000 deaths in 2011. PWE-018 HSPC1 INHIBITORS POTENTIATE THE EFFECT OF 5-FU IN PRIMARY COLORECTAL CANCER CELL MODEL1 Less than 50% of patients with Dukes stage C and D survive more than 5 years. Following treatment, cell metabolism rate and apoptosis were assessed using MTS and caspase-3 assay. Results In HT29, 17-DMAG was effective in i...

Background Quantitative faecal immunochemical tests (FIT) for haemoglobin are being used for colorectal cancer (CRC) screening for asymptomatic populations and are being indicated as a suitable test to rule out CRC in symptomatic populations. Faecal samples are typically collected by patients using a probe attached to the cap of a device which is inserted into a collection device into the preservative buffer, passing through a collar to remove excess sample: this process has potential for pre-analytical error. This study investigates whether faecal haemoglobin concentration (f-Hb) results are affected by the mass and method of sample collection. Methods Faecal samples with detectable f-Hb were loaded into collection devices from four manufacturers using increasing masses of sample. The f-Hb in the device buffer was measured using the relevant analyser. The results from the minimum recommended load were compared with results of 'sample overloading'. Results The variation in the faecal mass added to the probe (overall CVs: EXTEL HEMO AUTO-MC Collection Picker 300%, OC-Auto Sampling Bottle 3 237%, SENTiFIT pierceTube 264%, Specimen Collection Container A 250%), was more than the variation in f-Hb (respective overall CVs: 62%, 35%, 47%, 39%). The mass of faeces added to the probes increased significantly ( P < 0.0001 for all four devices), but the f-Hb did not increase significantly (EXTEL HEMO AUTO-MC Collection Picker P = 0.6820, OC-Auto Sampling Bottle 3 P = 0.9368, SENTiFIT pierceTube P = 0.7551, Specimen Collection Container A P = 0.6864). Conclusion The mass of sample loaded onto the probe did not impact the f-Hb significantly using all four tested devices.

ObjectivesExternal quality assessment schemes (EQAS) are being established worldwide to support the faecal immunochemical test (FIT) for haemoglobin (Hb). FIT is widely used as a screening test for colorectal cancer and increasingly in assessment of patients presenting with symptoms. EQA for FIT is provided in several matrices, each unique to the individual scheme. These include Hb suspended in a faecal-like matrix, lyophilised samples and liquid samples. The aim of this study was to evaluate commercially available EQAS and assess their suitability for use.MethodsTen EQAS provided material for the study. EQA samples were analysed on four quantitative FIT systems. 15 faecal-like matrix samples were loaded per concentration per FIT system. Reconstituted lyophilised samples were examined five times on three separate occasions and liquid samples were examined 10 times per concentration per FIT system. The coefficient of variation (CV) was calculated per concentration of EQA for each FIT system.ResultsResults from faecal-like matrix schemes had a higher median CV (12.4–19.0%) when compared to those from schemes providing liquid matrices (0.8–2.3%). The spread of CV values was also higher for results from faecal-like matrix schemes with an interquartile range (IQR) 4.4–24.0% vs. liquid IQR range of 0.3–2.5%.ConclusionsHb results from faecal-like matrices, whilst more aligned to a patient or participant sample, are prone to pre-examination variation so do not assess the analytical accuracy of a FIT system. Liquid matrices are not prone to pre-examination variation and are better able to assess the accuracy of a FIT system.

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Journal WatchPlasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia R Huijgen, SW Fouchier, M Denoun, et al. J Lipid Res 2012;53:979-83 Mutations in the genes coding for the LDL-receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) are now known to cause familial hypercholesterolaemia (FH). However, molecularly diagnosed FH patients do not always exhibit a hypercholesterolaemic phenotype. The reasons are largely unknown.The authors postulated that such non-penetrance of the FH mutation could, in part, be explained by the variation in PCSK9 activity. PCSK9 binds to the hepatic LDLR and thereby directs it towards degradation. Low activity of PCSK9 could lead to the increased presence of LDLR at the hepatic cell surface and, consequently, to the increased clearance of plasma LDL-cholesterol (LDL-C).Individuals (n ¼ 267) not on lipid-lowering medications were included. Those who had a pathogenic mutation were categorized based on their untreated LDL-C concentration. Those with an LDL-C below the age-and sexspecific 75th percentile were referred to as 'FH low'; those with an LDL-C above the 90th percentile were referred to as 'FH high'. First-degree relatives negative for the mutation were included as 'controls'. The study subjects also underwent examination of carotid arteries with ultrasound to assess intima-media thickness (cIMT).Individuals from the FH-low group had a significantly lower mean PCSK9 concentration (152 [137 -167] mg/L) compared with untreated individuals from the FH-high group (186 [165-207] mg/L, P ¼ 0.010) and controls (177 [164 -190] mg/L, P ¼ 0.013). Results were true after adjustment for age, gender, body mass index and systolic blood pressure. PCSK9 concentration was positively associated with cIMT after adjustment for the lipid profile and other traditional cardiovascular risk factors.The study was an observational study so a causal relationship between low plasma PCSK9 concentration and lower LDL-C could not be proven. However, plasma PCSK9 concentration may contribute to phenotypic variation in individuals with FH. Studies of pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited.