Adenomas as a risk factor in familial colorectal cancer: implications for screening and surveillance in the UK.

Colorectal cancer (CRC) develops from normal epithelium, through dysplastic adenoma to invasive carcinoma. In addition to familial adenomatous polyposis and Lynch syndrome, approximately 10-35% of CRCs are familial in nature. CRC screening and surveillance programmes are based on an understanding of the natural history of polyps and rely on the ability to remove premalignant lesions endoscopically before they are capable of developing invasion. There are, however, significant differences in these guidelines between the UK and the USA in relation to the weight attributed to a family history of polyps. Here, using publicly available national data sets, we show that these differences in guidelines unexpectedly generate inadequate screening recommendations for second-degree relatives of patients with CRC in the UK. We validate our simple mathematical modelling of the clinical problem on a regional data set as well as previously published study data to demonstrate the correct interpretation. We further discuss the implications of a family history of adenoma formation in the current climate of the Bowel Cancer Screening Programme and suggest a re-evaluation of the UK guidelines in the light of this developing issue.

Stem cells, quiescence and rectal carcinoma: an unexplored relationship and potential therapeutic target.

Stem cells are responsible for maintaining differentiated cell numbers during normal physiology and at times of tissue stress. They have the unique capabilities of proliferation, self-renewal, clonogenicity and multi-potentiality. It is a widely held belief that stem-like cells, known as cancer stem cells (CSCs), maintain tumours. The majority of currently identified intestinal stem cell populations appear to be rapidly cycling. However, quiescent stem cell populations have been suggested to exist in both normal intestinal crypts and tumours. Quiescent CSCs may have particular significance in the modern management of colorectal cancer making their identification and characterisation a priority. In this review, we discuss the current evidence surrounding the identification and microenvironmental control of stem cell populations in intestinal crypts and tumours as well as exploring the evidence supporting the existence of a quiescent stem and CSC population in the gut and other tissues.

Late epilepsy following open surgery for aneurysmal subarachnoid haemorrhage.

OBJECTIVE: To determine the risk for late epilepsy (>2 weeks postoperatively) following aneurysmal subarachnoid haemorrhage (SAH) treated by early aneurysm clipping. DESIGN: Subgroup analysis of the East Anglian regional audit of SAH (1994-2000; n = 872) with 12 month follow up. Prophylactic anticonvulsants were not routinely prescribed unless there was a perioperative seizure. SUBJECTS: 472 patients with aneurysmal SAH undergoing surgical clipping of the aneurysm were studied. Patients presenting in WFNS grade V, with space occupying haematomas requiring emergency surgery, or with posterior circulation aneurysms, rebleeds, and surgery after 21 days were excluded. RESULTS: Late epilepsy occurred in 23 patients (4.9%). There was a correlation between the incidence of late epilepsy and both the presenting WFNS grade (p<0.05) (grade 1, 1.4%; grade 2, 3.8%; grade 3, 9.6%; grade 4, 12.5%) and the Glasgow outcome score at discharge (p<0.01) (good recovery, 2.2%; moderate disability, 5.0%; severe disability, 15.5%). There was no relation between the incidence of late epilepsy and sex or the site of the aneurysm. CONCLUSIONS: The low incidence of late epilepsy following open surgery for aneurysmal SAH supports the withholding of prophylactic anticonvulsants. Patients with poor WFNS grade and poor recovery after surgery are at increased risk and should be closely monitored.