Competency based surgery.
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Competency-Based Education↗
Biomedical subjects
M Macluskey
Publications and source records attributed to M Macluskey.
Something to contribute.
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Hospitals, Teaching↗
Extraction of RNA from archival tissues and measurement of thrombospondin-1 mRNA in normal, dysplastic, and malignant oral tissues.
Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein implicated in the regulation of angiogenesis and tumour development. Our objectives were to ascertain the quantity and quality of RNA extracted from archival, formalin-fixed, paraffin embedded, oral tissues and their application in measuring the concentrations of TSP-1 mRNA in these tissues. We compared three techniques of isolation of RNA as well as related experimental variables. TSP-1 mRNA was measured in specimens of normal, dysplastic, and malignant oral tissues by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RNA suitable for analysis by real-time RT-PCR was obtained by the three techniques tested, although the yield varied depending on the protocol used (range 0.2-3.6 microg/mm(3)). The mean (S.D.) concentrations of TSP-1 mRNA relative to 18S were 21.1 (7.2) in normal oral tissues (n=9), 11.0 (8.2) in dysplastic tissue (n=8) and 7.3 (5.3) in carcinomatous tissue (n=17). The difference between normal and carcinomatous specimens was significant (p=0.01). This reduction in expression of TSP-1 mRNA from normal to dysplasia to carcinoma may favour the angiogenic drive that accompanies the development of oral tumours.
Carcinoma, Squamous Cell↗
Indications for and anticipated difficulty of third molar surgery: a comparison between a dental hospital and a specialist high street practice.
OBJECTIVE: To investigate the indications for and anticipated difficulty of third molar surgery between two different referral settings. DESIGN: A prospective study involving completion of a proforma pre- and post-operatively. SETTING: A dental teaching hospital and a specialist surgical dentistry practice in 2003. SUBJECTS AND METHODS: Patients referred for the assessment of their third molars were recruited. Details of the clinical and radiographical assessment for each patient were recorded pre-operatively and the extent of surgery required post-operatively. RESULTS: The main indication for referral for third molar extraction was pericoronitis in both centres. A larger number of patients were assessed and treated in a shorter period of time at the surgical dentist compared with the dental hospital. The surgical dentist was accurate in his assessment of the difficulty of surgery 96% of the time compared with 66% for the dental hospital staff. CONCLUSIONS: This study highlights the benefits for patients in being treated by a surgical dentist. As dental students require exposure to surgical dentistry in order to attain a level of competence, a reduction in the number of patients being referred to dental hospitals may impact upon students' ability to both assess and perform surgical procedures. This may mean that undergraduates will be less able to fulfil the recommendations of the General Dental Council. An outreach programme for final year dental students to surgical dentistry practices would benefit all concerned.
Adolescent↗
Vascularity and expression of vascular endothelial growth factor in oral squamous cell carcinoma, resection margins, and nodal metastases.
The role of vascularity as a predictor of the likelihood of lymph node metastases in oral cancer is not clear. To that end, the vascularity and expression of vascular endothelial growth factor (VEGF) was assessed at three specific regions: the tumour (inside and around the tumour); the resection margin; and the regional lymph nodes. Formalin-fixed paraffin-embedded specimens from 26 oral cancers (11 with no involved nodes and 15 with involved nodes) were stained immunohistochemically and examined. Staining for VEFG was significantly greater in the tumour than in the other sites. No significant differences were found in the intensity of staining in the primary tumour, resection margins, or nodes between cases in which the nodes were involved and in which they were not involved. We found no correlation between vascularity and VEGF staining, suggesting that VEGF is not the primary or only stimulator of angiogenesis in oral cancer. Greater understanding of the mechanisms of metastasis will lead to new treatments. The evidence that is accumulating for oral cancer suggests that such treatments may be better targeted at preventing lymphatic spread, rather than vascular spread.
Adult↗
The effect of the antibody used and method of quantification on oral mucosal vascularity.
A vast literature exists on angiogenesis particularly with regard to understanding tumour growth and development. This is no less true for oral cancer, where slight variations in protocols may invalidate comparison between studies. The influence of tissue processing, and the specific antibody and method of quantification used to identify blood vessels was assessed with respect to oral mucosal vascularity. The angiogenic profile of 20 frozen sections of clinically normal oral mucosa were compared with 16 paraffin-embedded specimens. Eight of the frozen specimens had matched paraffin-embedded tissue. Vascular antigens were identified immunohistochemically using four antibodies and blood vessel density was measured by three methods. CD31 and von Willebrand's factor (vWF) counts were higher than alpha-smooth muscle actin and alphanubeta3. Results for CD31 were higher in frozen tissue than paraffin-embedded tissue. Significantly more CD31-positive vessels were found in frozen tissue in the cohort of matched samples. For paraffin-embedded tissue vWF gave higher values for vascularity than CD31. The variation in antibody reaction to these markers of blood vessels suggests that the antibody employed and method of fixation is more important than the method of quantification used. Comparison of the results for fresh frozen tissue and paraffin-processed tissue suggests that this is acceptable for vWF but not for CD31.
Actins↗
Evidence for a field change effect based on angiogenesis in the oral mucosa? A brief report.
The concept of field cancerisation was proposed to explain the development of second primary tumours in the upper aerodigestive tract. The formation of new blood vessels (angiogenesis) has been shown to accompany oral disease progression, however, little is known about its potential role as an indicator of field cancerisation. The aims of this study were to compare the angiogenic profile of normal oral mucosa from oral cancer patients with that sampled from cancer-free patients to seek evidence for differences that might be termed a field change. Oral mucosal tissue (NC) was obtained from 25 oral cancer patients from a site at least 1 cm distant from the primary tumour and was compared with normal oral mucosa (NN) from a further 20 non-cancer patients. The vascularity of the tissue was investigated immunohistochemically using four antibodies and three methods of quantitation. Vascularity was significantly higher in the NC group than the NN with all four markers (p<0.01). Significantly higher indices of vascularity were found for patients who were smoker/drinkers in the NC group (p<0.05). The increased vascularity may provide a rationale for anti-angiogenic drug therapy for tertiary prevention.
Adolescent↗
Development of a structured clinical operative test (SCOT) in the assessment of practical ability in the oral surgery undergraduate curriculum.
Competence in undergraduate oral surgery involves assessment of the students' knowledge, practical skill and attitude. The assessment of practical skills can be achieved using a formative assessment method such as the structured clinical operative test (SCOT) which uses a checklist for the assessment of a clinical task. The aim of this study was primarily to determine whether SCOTs could be integrated into the oral surgery undergraduate course, and secondarily to collect feedback from both the students and the staff on this assessment. A validated checklist was used by trained examiners to assess the performance of 49 students in their second clinical year undertaking simple exodontia. Feedback was collected from the students by questionnaire and from the staff by interview. The SCOT was well received by both students and staff. The main problem highlighted by the students was the perceived inter-examiner variability and by the staff, the disruptive effect on the clinics. The checklist must be objective enough to prevent misinterpretation. Despite these limitations, the SCOT provides a more objective assessment and serves to highlight weaker students, allowing them to be targeted for closer supervision and instruction as well as providing the students with a tool to measure their progress in oral surgery. The use of peer assessment by students may alleviate the burden on the staff.
Clinical Competence↗
Expression of vascular endothelial growth factor in normal and tumour oral tissues assessed with different antibodies.
Expression of vascular endothelial growth factor (VEGF) in oral tissues was assessed using different antibodies. Quantitative and topographical differences were observed between paraffin and cryostat sections. Two polyclonal antibodies (PC36, PC37) differing in their cross-reactivity with VEGF121 (not recognized by PC36), were used to stain serial cryostat sections of normal oral mucosa (n = 8) and squamous cell carcinoma (n = 7). The expression of VEGF in the epithelium was overall higher with PC37 than with PC36, the difference being significant in normal oral mucosa (p = 0.001) but not in squamous cell carcinoma samples (p = 0.094). With PC36, VEGF expression was significantly higher in squamous cell carcinoma than in normal oral mucosa specimens, whereas the opposite was true with PC37. Our results suggest that the relative levels of isoform 121 to that of 165 (and possibly others) may be different in the tissues examined, with VEGF121 preferentially expressed in normal oral mucosa. Previously published conflicting results may, therefore, be due to the presence of variable ratios of VEGF isoforms in the tissues examined, combined with differences in the cross-reactivity of the antibodies used. VEGF isoforms 121, 165 and (for the first time) 189 were detected in two frozen oral tissues by polymerase chain reaction amplification. Quantification of specific VEGF isoforms will be required in future studies concerned with the clinical value of VEGF expression.
Antibodies↗
Vascular endothelial growth factor (VEGF) expression in oral tissues: possible relevance to angiogenesis, tumour progression and field cancerisation.
The aim of this study was to assess whether vascular endothelial growth factor (VEGF) expression in oral tissues is associated with angiogenesis, disease progression or field cancerisation. Vascularity and VEGF immunoreactivity were quantified in 68 archival specimens including normal oral mucosa (NOM), dysplasia (DYS) and squamous cell carcinoma (SCC). Vascularity increased significantly with disease progression; it was also higher in NOM adjacent to SCC than in NOM from healthy tissue, suggesting an association with field cancerisation. VEGF expression in epithelial cells was evaluated using two antibodies and three indices. VEGF indices and vascularity were not directly correlated. The expression of VEGF was similar in all DYS and NOM specimens, whether or not adjacent to a concurrent lesion. A comparison of SCC with NOM or DYS led to opposite results, depending on the VEGF antibody and index used. We conclude that VEGF expression in the oral mucosa may play a physiological role, but does not appear to be associated with angiogenesis, field cancerisation or transition to dysplasia. Further studies concerned with tumour development require examining specific VEGF isoforms and standardisation of the methodology.
Antibodies↗
Apoptosis, proliferation, and angiogenesis in oral tissues. Possible relevance to tumour progression.
Experimental animal models have demonstrated that angiogenesis is essential for tumour progression, whilst sustained tumour growth requires a positive balance between tumour cell proliferation and cell death (apoptosis). The aim of this study was to determine the relative contribution of apoptosis, proliferation, and angiogenesis to disease progression in the oral mucosa. Histological sections of 47 archival specimens were examined; these included four groups of oral tissues: normal mucosa (n=12), moderate dysplasia (n=11) severe dysplasia (n=6), and squamous cell carcinoma (n=18). Apoptotic cells were visualized by in-situ end-labelling of DNA, proliferative cells by staining with Ki-67 antibody, and blood vessels with von Willebrand factor (vWF) antibody. One-way analysis of variance showed that indices of apoptosis (AI), proliferation (PI), and angiogenesis (vascularity) increased significantly with disease progression from normal oral mucosa, through dysplasia, to carcinoma (p<0.0001 for every index). The increase from normal mucosa to moderate dysplasia was significant for PI and vascularity, but not for AI. In contrast, the increase from dysplasia to carcinoma was significant for AI and vascularity, but not for PI. These data suggest that disease progression in the oral mucosa is accompanied by angiogenesis and increases in both epithelial proliferation and apoptosis. Net epithelial growth results from proliferation starting earlier and proceeding at a higher rate than apoptosis.
Adolescent↗
An overview of the prevention of oral cancer and diagnostic markers of malignant change: 1. Prevention.
The incidence of oral cancer appears to be on the increase, with patients presenting at an earlier age. An overview of the prevention of this important condition is given in this article, and diagnostic markers will be discussed in a later presentation. Greater awareness of the aetiological agents involved in the development of oral cancer, and their avoidance, should help reduce the number of cases. General dental practitioners have an important role to play in advising patients on healthier lifestyles (primary prevention), the detection of potentially malignant disease before it becomes malignant (secondary prevention) and screening for field changes in patients with a history of oral cancer. The role of chemoprevention (defined here as tertiary prevention) is also considered.
Carcinoma, Squamous Cell↗
An overview of the prevention of oral cancer and diagnostic markers of malignant change: 2. Markers of value in tumour diagnosis.
Earlier diagnosis of oral cancer should lead to an improvement in prognosis. This, the second part of a two-part overview, is concerned with the various cellular markers available for diagnosis of oral cancer. Traditionally diagnosis has relied upon the histomorphological interpretation of a tissue section following biopsy. The application of advances in various laboratory techniques for the identification of different cellular markers is briefly reviewed. In addition, although it is currently only a research tool, the potential role of oral exfoliative cytology in screening is considered.
Antigens, Neoplasm↗
The association between epithelial proliferation and disease progression in the oral mucosa.
The purpose of this study was to examine the possible association between epithelial proliferation and disease progression in the oral mucosa. Archival specimens of normal oral mucosa (n = 12), dysplasia (n = 17) and squamous cell carcinoma (n = 18) were sectioned and proliferating cells visualised by staining with Ki-67 antibody. The proliferative index of the epithelium (PI) was determined by total cell counts and point counting. Similar results were obtained using either method. Comparison of the three groups of tissues by one-way analysis of variance showed a significant increase in PI with increasing lesion severity (p < 0.001). The PI of both dysplasia and carcinoma groups was significantly higher than that of normal oral mucosa (p < 0.001). However, the difference between dysplasia and carcinoma groups was not significant. PI was not associated with tobacco or alcohol consumption. We therefore conclude that Ki-67 expression is an early marker of disease progression in the oral mucosa but, on its own, is not a good indicator of neoplastic transformation.
Adult↗
High levels of apoptosis are associated with improved survival in non-small cell lung cancer.
Tumour growth is accompanied by angiogenesis and reduced apoptosis in experimental animals. The aim of this study was to examine the prognostic value of apoptosis and the association between apoptosis and vascularity in non-small cell lung cancer (NSCLC). Following in-situ end-labelling of DNA, apoptotic cells were quantified by three different indices: as a percentage, either counting total cells (AI-tc) or point-counting (AI-pc), or as cells per area (AI-area). Blood vessels were stained with vWF antibody and vascularity was quantified by three methods. Median values for AI-tc, AI-pc and AI-area were 0.38, 0.32 and 10.7, respectively. High values were associated with improved survival, reaching statistical significance for AI-area (p < 0.05). All three apoptotic indices were significantly correlated with each other, but no correlation was found between indices of apoptosis and vascularity. As previously reported, vascularity had no prognostic value. These results indicate that, in NSCLC, vascularity is not informative, but apoptotic index may be a useful prognostic factor.
Adenocarcinoma↗