Recent advances indicate that the widespread use of biomarkers may herald the next major advance in the diagnosis and management of CRC.

Overall, 68% of colonoscopies were on time. The incidence of colorectal cancer was greatly reduced by screening but remained significant. Patients with Lynch syndrome need proactive surveillance management.

A regular systematic large bowel screening programme, managed by a Polyposis Registry, significantly improves the prognosis of FAP.

Background & Aims Lynch syndrome patients have DNA mismatch repair deficiency and up to 80% life-time risk of colorectal cancer. Screening of mutation carriers reduces colorectal cancer incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from Lynch Syndrome (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of mutations. Methods Tumour DNA was extracted (FFPE tissue) and pyrosequencing used to test for MLH1 promoter methylation and presence of the BRAF c.1799T>A, p.(Val600Glu) mutation 71 CRCs from individuals with pathogenic MLH1 mutations and 73 CRCs with sporadic MLH1 loss. Specificity and sensitivity was compared. Findings Unmethylated MLH1 promoter: sensitivity 94.4% (95% CI 86.2–98.4%), specificity 87.7% (95% CI 77.9–94.2%), Wild-type BRAF (codon 600): sensitivity 65.8% (95% CI 53.7–76.5%), specificity 98.6% (95% CI 92.4–100.0%) for the identification of those with pathogenic MLH1 mutations. Conclusions Quantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours.

Familial adenomatous polyposis (FAP) has been divided into three clinical subtypes: mild, classical and severe. This study aimed to investigate for a correlation between genotype and phenotype. A codon-specific survival difference is unknown. A retrospective longitudinal study of 492 patients on the Manchester Polyposis Registry was conducted. Patients were grouped according to genotypes: 0, unknown mutation; 1, adenomatous polyposis coli (APC) 0-178 (and 312-412 of exon 9); 2, APC >1550; 3, APC 179-1249; 4, APC 1250-1549; and 5, MutYH. Date of onset of polyposis, incidence of colorectal cancer (CRC), survival and actuarial time to surgery were calculated. Median age of onset of polyposis for genotype 0 was 20.3 years, genotype 1 35.6 years, genotype 2 32.2, genotype 3 15.9 years, and genotype 4 14.8 years (p < 0.0001). Age of onset of CRC was similar between genotypes. Median survival for genotype 0 was 56.6 years, genotype 1 74.9 years, genotype 2 61.0 years, genotype 3 63.0 years, genotype 4 48.1 years, and genotype 5 69.7 years (p = 0.003). This survival difference was also seen when patients who underwent screening and those who did not were analysed separately. Survival in the screened population was 53.9 years in genotype 4 and 72.9 years in genotype 3. Patients with genotype 4 (APC 1249-1549) have a significantly worse survival despite screening and early prophylactic surgery. This analysis supports a genotype-phenotype correlation. Patients with a mutation APC 1249-1549 develop polyposis at an early age and have a worse survival. Patients with a mutation APC 0-178 or 312-412 develop polyposis later and have an improved survival. This survival difference has not previously been documented.

INTRODUCTION The spleen remains one of the most frequently injured organs following blunt abdominal trauma. In 2012, regional trauma networks were launched across England and Wales with the aim of improving outcomes following trauma. This retrospective cohort study investigated the management and outcomes of blunt splenic injuries before and after the establishment of regional trauma networks. METHODS A dataset was drawn from the Trauma Audit Research Network database of all splenic injuries admitted to English and Welsh hospitals from 1 April 2010 to 31 March 2014. Demographic data, injury severity, treatment modalities and outcomes were collected. Management and outcomes were compared before and after the launch of regional trauma networks. RESULTS There were 1457 blunt splenic injuries: 575 between 2010 and 2012 and 882 in 2012-14. Following the introduction of the regional trauma networks, use of splenic artery embolotherapy increased from 3.5% to 7.6% (P = 0.001) and splenectomy rates decreased from 20% to 14.85% (P = 0.012). Significantly more patients with polytrauma and blunt splenic injury were treated with splenic embolotherapy following 2012 (61.2% vs. 30%, P < 0.0001). Increasing age, injury severity score, polytrauma and Charlson Comorbidity Index above 10 were predictors of increased mortality (P < 0.001). Increasing systolic blood pressure (odds ratio, OR, 0.757, 95% confidence interval, CI, 0.716-0.8) and Glasgow Coma Scale (OR 0.988, 95% CI 0.982-0.995) were protective. CONCLUSIONS This study demonstrates a reduction in splenectomy rate and an increased use of splenic artery embolotherapy since the introduction of the regional trauma networks. This may have resulted from improved access to specialist services and reduced practice variation since the establishment of these networks.

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Given the low efficacy of treatments for desmoids in FAP, radiofrequency ablation appears to be a promising modality.