Results from a prospective, randomised study on (accelerated) preoperative versus (conventional) postoperative radiotherapy in treatment of patients with resectable squamous cell carcinoma of the oral cavity - The ARTSCAN 2 study.

BACKGROUND AND PURPOSE: An earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed. MATERIALS AND METHODS: Patients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6-7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed. RESULTS: 250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65-82) in preoperative AF and 78% (95% CI, 70-85) in postoperative CF. Toxicity was more pronounced in preoperative AF. CONCLUSION: This study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.

High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue.

BACKGROUND: p63 proteins are important in formation of the oral mucosa. Normal oral mucosa shows a balance between the six protein isoforms, whereas an imbalance between them is seen in squamous cell carcinomas (SCC). There is controversy over the clinical impact of p63 in SCC, which may relate to different expression in different areas. In addition, p63 isoforms can act as p53-like molecules (TAp63) or can inhibit p53 functions (ΔNp63) and expression of these isoforms varies in different tumours. Here, we chose to concentrate on the most common intra-oral sub-site, SCC of the mobile tongue. METHODS: Total p63, ΔNp63 and TAp63 were analysed separately using immunohistochemistry. The percentage of cells and intensity of expression of different isoforms of p63 was evaluated using a quick score method and correlated with clinical data in a group of 87 patients with tongue SCC. RESULTS: All tumours expressed p63 in at least 60% of the cells when using two different antibodies detecting all 6 isoforms. p63 expression correlated significantly with 2-year survival (P = 0.018), with fewer patients surviving 2 years if their tumours expressed p63 with strong intensity in at least 80% of the cells (quick score 18). Looking at 5-year survival, this was even more emphasized. ΔNp63 was expressed in all tumours, whereas expression of TAp63 was seen only in 59/87 patients, usually at very low levels. CONCLUSIONS: Based on the present data, we recommend using expression of p63 as an additional factor contributing prognostic information in analysis of SCC in the tongue.

Subsite-based alterations in miR-21, miR-125b, and miR-203 in squamous cell carcinoma of the oral cavity and correlation to important target proteins.

BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNA molecules with an essential role in regulation of gene expression. miRNA expression profiles differ between tumor and normal control tissue in many types of cancers and miRNA profiling is seen as a promising field for finding new diagnostic and prognostic tools. MATERIALS AND METHODS: In this study, we have analyzed expression of three miRNAs, miR-21, miR-125b, and miR-203, and their potential target proteins p53 and p63, known to be deregulated in squamous cell carcinoma of the head and neck (SCCHN), in two distinct and one mixed subsite in squamous cell carcinoma in the oral cavity. RESULTS: We demonstrate that levels of miRNA differ between tumors of different subsites with tongue tumors showing significant deregulation of all three miRNAs, whereas gingival tumors only showed significant downregulation of miR-125b and the mixed group of tumors in tongue/floor of the mouth showed significant deregulation of miR-21 and miR-125b. In the whole group of oral squamous cell carcinoma (SCC), a significant negative correlation was seen between miR-125b and p53 as well as a significant correlation between TP53 mutation status and miR-125b. CONCLUSION: The present data once again emphasize the need to take subsite into consideration when analyzing oral SCC and clearly show that data from in vitro studies cannot be transferred directly to the in vivo situation.

Hot water surface pasteurisation of lamb carcasses: microbial effects and cost-benefit considerations.

Although hot water pasteurisation of carcasses is accepted as a general intervention in USA, this is not the case in Europe. The aims of this study were (i) to evaluate the microbiological effects of hot water pasteurisation of lamb carcasses, both after slaughtering and dressing and following subsequent chilling and storage; (ii) to discuss hot water pasteurisation from a public health and cost-benefit perspective; (iii) to discuss the benefits of hot water pasteurisation compared with use of separate meat processing streams for high-risk carcasses; (iv) to evaluate the use of recycled hot water in a hygienic context and in relation to EU regulations; and (v) to consider the technological and sensory aspects of hot water pasteurisation of lamb carcasses. Samples were collected from 420 naturally contaminated lamb carcasses, with 50% of the carcasses (n=210) subject to hot water pasteurisation at 82 °C for 8s immediately after slaughter. Surface swab samples from 4500 cm² areas on carcasses were collected at slaughter, after chilling for 24 h, and after chilling for five days. The microbial analyses included Escherichia coli, Enterobacteriaceae, Bacillus cereus, Clostridium perfringens and aerobic plate count (APC). A resuscitation step using Tryptone Soya Agar was included in the microbiological analyses. Hot water pasteurisation significantly reduced the levels of E. coli, Enterobacteriaceae, B. cereus and APC (all P<0.001). E. coli colony forming unit (CFU) reduction was 99.5%, corresponding to a reduction of 1.85 log CFU per carcass. E. coli was isolated from 66% of control carcasses and from 26% of pasteurised carcasses. After 24h storage, the reduction in E. coli was increased to 2.02 log, and after five days E. coli could not be isolated from the pasteurised carcasses. These results suggest that surface pasteurisation could be an important and efficient procedure (critical control point) for reducing generic E. coli and thereby shiga toxin-producing E. coli on carcasses, and thus the risk for disease among consumers. The recycled water had acceptable physical and chemical parameters and no spore-forming bacteria were detected. Although some carcass discolouration was observed, after 24h the colour was acceptable. Our data provide relevant input for some of the data gaps regarding hot water pasteurisation and indicate that replacing the expensive system of separate processing of high-risk carcasses with hot water surface pasteurisation should be considered as a serious option.