Loss of CD151/Tspan24 from the complex with integrin α3ß1 in invasive front of the tumour is a negative predictor of disease-free survival in oral squamous cell carcinoma.

OBJECTIVES: The study aimed to assess the role of CD151-integrin α3ß1 (INGA3) complex as a potential prognostic indicator in OSCC and to examine whether mapping of its expression in the invasive front separately from that in the rest of the tumour would have an impact on the predictive value of the results. CD151/INGA3 profiles were compared with that of EGFR. MATERIALS AND METHODS: Protein distributions were analysed either in the whole tumour (W) or separately, (i) the main tumour mass (TU) and (ii) the invasive front (IF) in 83 OSCC samples using immunohistochemistry. RESULTS AND CONCLUSION: There was no statistical association between any of the proteins scored in W and clinicopathologic features or patient survival. When examined separately, significant associations were shown for (i) CD151 and EGFR in TU (p=0.036) and (ii) tumour grade and EGFR in both TU (p=0.045) and IF (p=0.030). INGA3 was present predominantly in the tumour-host interface, significantly stronger in IF than TU (p=0.021). An association with 5-year disease-free survival was close to significant for INGA3 (TU and IF) (p=0.050) but not the CD151/INGA3 complex. Expression of CD151/INGA3 at the IF might reflect tumour behaviour pertinent to patient outcome.

A study of split-dose cisplatin-based neo-adjuvant chemotherapy in muscle-invasive bladder cancer.

The aim of this study was to investigate the outcome of patients with muscle-invasive bladder cancer (MIBC) receiving neo-adjuvant chemotherapy (neo-CT) using a cisplatin-based regimen fractionated on days 1 and 8 of a 21-day cycle prior to organ-preservation (chemoradiation) or cystectomy. Patients with stage T2-T4, N0, M0, transitional cell carcinoma (TCC) of the bladder with a calculated glomerular filtration rate (GFR) ≥40 ml/min were eligible for inclusion in the study. Neo-CT comprised of gemcitabine (1,000 mg/m(2) d1, d8, q21) plus cisplatin (35 mg/m(2) d1, d8, q21) for four cycles. Following the administration of neo-CT, patients underwent surgery or radiotherapy (RT) with or without concurrent chemotherapy (CRT), based on the response to neo-CT and clinician and patient preference. A total of 23 patients were recruited: 21 males and 2 females; median age, 69 years (range, 49-85); stage T2=11, T3A=7, T3B=5, grade 2=1, grade 3=22. One patient progressed prior to neo-CT. In total, 75 cycles of neo-CT were administered. Treatment was well-tolerated with only one episode of neutropenic sepsis. Three of 22 patients developed early progression and did not receive radical treatment. For the remaining 19 patients, choice of definitive treatment (surgery vs. RT/CRT) was based on response to neo-CT. Eight patients had residual disease at cystoscopy following the completion of neo-CT; six patients underwent surgery and two underwent RT/CRT. A total of 11 patients had a complete response (CR) to neo-CT, nine of whom were treated by RT/CRT, with the remaining two declining radical treatment. Median follow-up for alive patients was 57 months (range, 4.4-68.5). Three-year survival was 37% (95% CI 17-58%) and 5-year survival was 31% (95% CI 15-52%). Neo-CT is effective and well-tolerated in MIBC. This split-dose cisplatin regimen facilitates treatment in an outpatient setting and allows inclusion of patients with compromised GFR.

Smoking initiation is followed by the early acquisition of epigenetic change in cervical epithelium: a longitudinal study.

BACKGROUND: To prove a causal link between an epigenetic change and an environmental or behavioural risk factor for a given disease, it is first necessary to show that the onset of exposure precedes the first detection of that epigenetic change in subjects who are still free of disease. METHODS: Towards this end, a cohort of women aged 15-19 years, recruited soon after they first had sexual intercourse, were used to provide sequential observations on the relationship between cigarette smoking and the detection in cervical cytological samples of methylated forms of CDKN2A (p16) using nested methylation-specific polymerase chain reaction. RESULTS: Among women who remained cytologically normal and who tested negative for human papillomavirus DNA in cervical smears during follow-up, those who first started to smoke during follow-up had an increased risk of acquiring CDKN2A methylation compared with never-smokers (odds ratio=3.67; 95% confidence interval 1.09-12.33; P=0.04). CONCLUSION: Smoking initiation is associated with the appearance of methylated forms of CDKN2A.

The impact of psoriasis guidelines on appropriateness of referral from primary to secondary care: a randomized controlled trial.

BACKGROUND: Most patients with psoriasis have limited disease which can be managed effectively in primary care. There is a marked variation in the frequency of referrals between practices reflecting, in part, inadequate training of general practitioners (GPs) in the management of psoriasis. OBJECTIVES: To assess the effectiveness of guidelines and training sessions on the management of psoriasis in reducing inappropriate referrals from primary care. METHODS: Patients aged 18 years or over with psoriasis were eligible for the cluster-randomized, randomized controlled trial if they were referred by their GP between 9 September 2002 and 31 December 2003 to one of four hospital dermatology departments in Greater Manchester, North-West England. All GPs from 165 health centres were invited to a lecture by a local dermatologist on the diagnosis and management of psoriasis. Health centres in the intervention arm received guidelines on the management of psoriasis in primary care, developed by local dermatologists, supplemented by the offer of a practice-based nurse-led training session; those in the control arm received neither guidelines nor training sessions. RESULTS: Eighty-two health centres were randomized to the intervention arm and 83 to the control arm. Outcome data were available for 188 of the 196 eligible patients referred during the study period. Patients in the intervention arm were significantly more likely to be appropriately referred in comparison with patients in the control arm [difference = 19.1%; odds ratio (OR) 2.47; 95% confidence interval (CI) 1.31-4.68; intracluster correlation coefficient (ICC) = 0]. Only 25 (30%) health centres in the intervention arm took up the offer of training sessions. There was no significant difference in outcome between health centres in the intervention arm that received a training session and those that did not (OR 1.28, 95% CI 0.50-3.29, ICC = 0). CONCLUSIONS: Dissemination of guidelines on the management of psoriasis in primary care can significantly enhance the appropriateness of referral of patients to secondary care.