Laryngeal dysplasia: a 10-year review of rates of progression to invasive carcinoma and treatment-specific outcomes in a regional ENT department in Northern Ireland.

BACKGROUND: Laryngeal dysplasia represents a complex pre-malignant condition characterised by a spectrum of mucosal changes, with a reported malignant transformation rate from dysplasia to invasive carcinoma of 14.0 per cent. OBJECTIVE: To identify whether increasing glottic dysplasia severity is associated with higher local malignant transformation rates or adverse clinical outcomes. METHODS: This retrospective cohort study identified 125 patients with any histopathological grade of glottic dysplasia over a 10-year period who were followed up for a standardised 10-year period. RESULTS: The malignant transformation rate was 21.8 per cent over 10 years, demonstrating a statistically significant greater risk with increasing dysplasia severity. The mean time to transformation was 52 months, with time to transformation statistically associated with increasing dysplasia severity. Rapid progression to carcinoma within 12 months occurred in 40 per cent of cases, and 58 per cent of subsequently diagnosed laryngeal squamous cell carcinomas were tumour stage T1. CONCLUSION: Laryngeal dysplasia carries a significant malignant potential, appearing greatest within 12 months of diagnosis and with increasing severity of dysplasia.

Thromboelastography (TEG®) demonstrates that tinzaparin 4500 international units has no detectable anticoagulant activity after caesarean section.

BACKGROUND: Low molecular weight heparin is routinely used for thromboprophylaxis in pregnancy and the puerperium. Consensus guidelines recommend waiting 10-12h after administration of a thromboprophylactic dose of low molecular weight heparin before performing a neuraxial block or removing an epidural catheter. Thromboelastography (TEG®) has been reported to be sensitive to the effects of enoxaparin 4h after administration. The purpose of this study was to use TEG to examine coagulation changes in the first 10h after a thromboprophylactic dose of tinzaparin in an attempt to ratify the current consensus guidelines about timing of neuraxial blockade and epidural catheter removal. METHODS: Twenty-four women who had undergone caesarean delivery and were classified as low or intermediate risk of thrombosis were recruited. Blood samples were taken before subcutaneous administration of tinzaparin 4500IU, and at 4, 8 and 10h post-dose. Standard TEG analyses were performed using plain and heparinase cuvettes and samples were also sent for laboratory anti-Xa assay. Thromboelastograph profiles were analysed for a low molecular weight heparin effect. RESULTS: Analysis revealed no significant differences in R time, K time, alpha angle or maximum amplitude between plain and heparinase samples at any time point. Apart from a small statistically significant (P=0.033) decrease in maximum amplitude of 2.8% (95% CI 0.3 to 5.4%) at 4h, there were no significant changes in coagulation for any TEG parameter. Anti-Xa levels were virtually undetectable in all patients over the 10h period (median 0.00U/mL; range 0.00-0.13U/mL). CONCLUSION: A thromboprophylactic dose of tinzaparin 4500IU had little detectable effect on coagulation as assessed by TEG and anti-Xa assay. These findings support consensus guidelines which state that it is acceptable to perform neuraxial blockade or remove an epidural catheter 10-12h after a thromboprophylactic dose of tinzaparin. Rather than suggesting a lack of anticoagulant activity, the findings indicate that TEG may not have the sensitivity to detect a tinzaparin effect when this dose is used in this patient group.

p53, Cyclin D1, p21 (WAF1) and Ki-67 (MIB1) Expression at Invasive Tumour Fronts of Oral Squamous Cell Carcinomas and Development of Local Recurrence.

BACKGROUND: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence. MATERIALS AND METHODS: Archived paraffin-embedded specimens from 51 patients with T1/T2 tumours were stained immunohistochemically and analysed quantitatively. Local recurrence-free survival was tested with Kaplan-Meier survival plots (log-rank test) using median values to define low and high expression groups and with a Cox's proportional hazards model in which the expression scores were entered as continuous variables. RESULTS: The assessment of expression of all markers was highly reliable, univariate analysis showing that patients with clear surgical margins, with low cyclin D1 and high p21 expression at the ITF had the best local recurrence-free survival. Multivariate analysis showed that these three parameters were independent prognostic factors but that neither p53 nor MIB1 expression were of prognostic value. CONCLUSIONS: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases.

Checking pregnancy status in adolescent girls before procedures under general anaesthesia.

OBJECTIVE: Surgery, ionising radiation and anaesthesia in the presence of an undetected pregnancy could be harmful. British guidelines state that female patients of 'childbearing age' should have their pregnancy status established before surgery. Approaching this topic with an adolescent girl can be challenging. DESIGN: The authors conducted an observational study and a survey in their institution and a national survey of Association of Paediatric Anaesthetists (APA) linkmen. SETTING: Local: Southampton. National: UK. RESULTS: Both surveys demonstrate widespread concerns about inconsistent and informal practices. Only 45% of respondents in the authors' institution stated they ask adolescent girls if they could be pregnant. 40% of APA linkmen were unaware of national guidelines. CONCLUSIONS: This work illustrates the need for consistent national guidance. We propose that all girls who have reached menarche should be routinely offered a urine pregnancy test before any procedure under general anaesthesia.

Clinical medical sciences for undergraduate dental students in the United Kingdom and Ireland - a curriculum.

The technical aspects of dentistry need to be practised with insight into the spectrum of human diseases and illnesses and how these impact upon individuals and society. Application of this insight is critical to decision-making related to the planning and delivery of safe and appropriate patient-centred healthcare tailored to the needs of the individual. Provision for the necessary training is included in undergraduate programmes, but in the United Kingdom and Ireland there is considerable variation between centres without common outcomes. In 2009 representatives from 17 undergraduate dental schools in the United Kingdom and Ireland agreed to move towards a common, shared approach to meet their own immediate needs and that might also be of value to others in keeping with the Bologna Process. To provide a clear identity the term 'Clinical Medical Sciences in Dentistry' was agreed in preference to other names such as 'Human Disease' or 'Medicine and Surgery'. The group was challenged to define consensus outcomes. Contemporary dental education documents informed, but did not drive the process. The consensus curriculum for undergraduate Clinical Medical Sciences in Dentistry teaching agreed by the participating centres is reported. Many of the issues are generic and it includes elements that are likely to be applicable to others. This document will act as a focus for a more unified approach to the outcomes required by graduates of the participating centres and act as a catalyst for future developments that ultimately aim to enhance the quality of patient care.

Something not quite right: Gardner syndrome diagnosed by multiple cutaneous lesions and genetic testing.

Gardner syndrome is a variant of familial adenomatous polyposis characterized by intestinal adenomatous polyps, which can progress to adenocarcinoma, and a variety of extraintestinal manifestations, including skin cysts, osteomas, soft tissue fibrous tumours and a characteristic ocular lesion. The extraintestinal manifestations are often the presenting feature but are usually not sufficiently characteristic on their own to trigger recognition of the syndrome. We report a case of a 17-year-old female who had been treated by a number of specialists over a 13-year period for a variety of cutaneous lesions without a hereditary condition being suspected. Gardner syndrome was considered only after excision of subcutaneous fibrous tumours from the mastoid region and paraspinal area and was confirmed by genetic testing in spite of the patient's refusal to undergo colonic endoscopic examination. Subsequent resection revealed approximately 70 adenomatous colonic polyps in the colon and rectum but no invasive tumour, highlighting the benefits of genetic testing in treatment planning.

Potentially malignant oral lesions in Northern Ireland: size (extent) matters.

OBJECTIVES: We examined clinical parameters of patients from Northern Ireland with potentially malignant lesions (PML) to determine association with development of intraoral squamous cell carcinoma (SCC). DESIGN: retrospective, cross-sectional, population-based, clinically validated, laboratory-verified. SUBJECTS AND METHODS: All patients who had more than one incisional oral mucosal biopsy diagnosed from 1975-1991 were abstracted from a database of all PML and SCC and their clinical records and biopsies reviewed. Patients were excluded if there was priorlsynchronous SCC or radiotherapy, frictional keratosis or lichen planus, missing clinical records/biopsy material or follow-up of <24 months. From the 50 suitable patients, gender, age, smoking status, site, clinical appearance and extent of lesion(s), treatment and year of diagnosis were recorded. Patients who developed SCC from PML were compared with those who did not. RESULTS: Squamous cell carcinoma occurred significantly more often in patients with single rather than multiple PML, those with 'non-homogenous' PML and in patients diagnosed prior to 1980. In Cox's survival analysis, only the clinical extent was predictive of SCC. CONCLUSIONS: Of all the features considered in our series, size (extent) was the most important clinical factor in determining the risk of future SCC in PML, particularly when several adjacent anatomical sites were affected.

Paradental cysts: a role for food impaction in the pathogenesis? A review of cases from Northern Ireland.

We present the clinical, radiographic and histological findings of 15 paradental cysts. These were the second most common type of cyst associated with mandibular third molars, comprising 25% of all lesions at this site. Ten patients were aged 30 years or younger and 13 gave a history of pericoronitis. There was a close relationship between the site of the cyst and the angle of the impacted tooth; the cyst lay mesially to two mesioangularly impacted teeth, buccal to two vertically impacted teeth and distal/distobuccal to the remainder, all but one of which were distoangular in impaction. The pericoronal follicular space was preserved in nine cases, a useful diagnostic sign. Most cysts were lined with epithelium that resembled that seen in radicular cysts, although the lining of three cysts resembled that of unicystic ameloblastoma, a potential diagnostic pitfall. We propose that the relation between location of cyst and angle of impaction points to a role for food impaction in the pathogenesis of paradental cysts.

Suprabasal p53 immunoexpression is strongly associated with high grade dysplasia and risk for malignant transformation in potentially malignant oral lesions from Northern Ireland.

AIMS: No good predictive marker for the malignant transformation of potentially malignant oral lesions (PMOLs) is currently available. This study re-evaluated the value of p53 immunoexpression to predict malignant transformation of PMOLs after discounting possible confounding factors. METHODS: PMOLs from 18 patients who showed progression to carcinoma, 16 of the respective carcinomas, and PMOLs from 18 matched controls were evaluated by immunohistochemistry (IHC) for p53 expression. A mouse monoclonal antibody that detects wild-type and mutant forms of human p53 was used. The p53 immunostaining pattern was also correlated with the degree of dysplasia. RESULTS: Suprabasal p53 staining was significantly associated with high grades of dysplasia (p < 0.01). The specificity and positive predictive value (PPV) for malignant transformation of suprabasal p53 staining were superior to the assessment of dysplasia, but sensitivity was inferior. All carcinomas derived from PMOLs with suprabasal p53 showed strong p53 immunostaining. However, the absence of suprabasal p53 staining and/or dysplastic changes did not preclude malignant transformation in a considerable proportion of PMOLs. CONCLUSIONS: This study confirms and extends previous findings that suprabasal p53 immunoexpression has a high PPV for malignant transformation of PMOLs and can be used as a specific marker for lesions that are at high risk for malignant transformation. The absence of suprabasal p53 staining (that is, absence of, or basal, p53 staining) is non-informative for prognostic purposes. Because of its limited sensitivity, p53 IHC is not a substitute for the assessment of dysplasia in the evaluation of PMOLs. Instead, p53 IHC emerges as a clinically useful supplement of histopathological assessment in the prognosis of PMOLs.

Potentially malignant oral lesions in northern Ireland: a 20-year population-based perspective of malignant transformation.

This retrospective laboratory-based study investigates the potential for malignant transformation of oral mucosal lesions in a population of 1.6 million. Over the 20-year period there were 745 patients diagnosed with primary intra-oral squamous cell carcinoma (OSCC), 165 patients with dysplasia and 1182 patients with 'non-dysplastic' lesions (epithelial hyperplasia, hyperkeratosis epithelial atrophy, lichen planus and lupus erythematosus). Malignant transformation occurred in 15% of dysplasias and in 1% of 'non-dysplastic' lesions at average intervals after diagnosis of 48 and 65 months respectively. Only 6% of patients with OSCC had a pre-invasive lesion biopsied. These data suggest that white lesions are only rarely the pre-invasive phase of OSCC. It is possible therefore that early changes are red, small or even microscopic with carcinoma developing without a clinically observable phase. More effective management strategies will require the development of tissue markers to enhance early detection.

Bcl-2 expression in sequential biopsies of potentially malignant oral mucosal lesions assessed by immunocytochemistry.

OBJECTIVE: To examine, for the first time Bcl-2 expression in sequential (autogenous) oral mucosal biopsies taken from the same sites in a gender, risk-factor matched, Caucasoid sample, over a 21-year period. DESIGN: Retrospective immunocytochemical longitudinal study of archival serial biopsies. MATERIALS AND METHODS: Computer records were used to identify biopsy specimens derived from 12 patients. These were divided into four groups: (1) Histologically innocuous lesions which remained histologically innocuous. (2) Dysplastic lesions which remained dysplastic. (3) Histologically innocuous lesions which later progressed to squamous cell carcinoma (SCC). (4) Dysplastic lesions which later progressed to SCC. This represented 65 biopsies in total. Bcl-2 expression was studied using mouse antihuman BCL-2 oncoprotein clone 124 (Dako, Denmark). RESULTS: Generally, there was a lack of Bcl-2 immunoreactivity in the epithelium, with one exception in dysplastic epithelium from a group (3) patient. CONCLUSION: These findings suggest that in our series, Bcl-2 is not expressed early in oral premalignant lesions and appears to contradict previous reports. Possible explanations for this disparity are considered.

Odontogenic keratocysts in a 5-year-old: initial manifestations of nevoid basal cell carcinoma syndrome.

The purpose of this paper is to report the occurrence of odontogenic keratocysts in a young child. Odontogenic keratocysts are one of the principal features of nevoid basal cell carcinoma syndrome. Their occurrence in this syndrome is usually during the second or third decades of life. This report describes the occurrence of odontogenic keratocysts in a 5-year-old, which proved to be the initial presentation of nevoid basal cell carcinoma syndrome and highlights the need to consider this syndrome as a possible diagnosis in all cases of odontogenic keratocysts.

Results from the international evaluation exercise for uranium enrichment measurements. European Safeguards Research and Development Association NDA-WG Members

An international evaluation exercise for uranium enrichment measurement was organized by the ESARDA (European Safeguards Research and Development Association) Working Group on Techniques and Standards for Non-Destructive Analysis. The aim of this exercise was to test the different methods and more particularly X- and gamma-ray spectrometry methods used in the determination of uranium enrichment. Sets of samples of different uranium enrichments prepared by IRMM (Institute for Reference Materials and Measurements) and BNFL (British Nuclear Fuels) were measured by 15 participants in the IRMM laboratories. A description of this exercise is given here and the final results with their uncertainties are compared to the reference values obtained from mass spectrometry measurements. The main conclusions from this exercise are proposed; in particular, it appears necessary to improve the nuclear data used in the spectral modeling of the XKalpha region.

Oral white sponge naevus: response to antibiotic therapy.

White sponge naevus is a rare benign inherited disorder of the mucous membranes, principally the oral mucosa. Although the condition is painless, patients are often symptomatic, complaining of an altered texture of the mucosa or that the lesions are unaesthetic. No standard treatment for the condition exists although numerous treatments have been tried. We now report on six patients who were prescribed systemic antibiotic therapy; three were adult men aged 24 years, 32 years, and 52 years, one an 11-year-old woman, one a 6-year-old woman (daughter of the 32-year-old man) and an 18-month-old boy (son of the 24-year-old man). Four responded as judged by clinical examination, although not the 6-year-old female or the 18-month-old male; the discontinuation of therapy then resulted in clinical recurrence in those who had responded, but long-term low dose treatment maintained the remission.

Cheilo-candidosis in an adult.

A rare case of candidal infection of the lips is presented. Predisposing factors appeared to be intra-oral candidal carriage, actinic lip damage and Sjögren's syndrome. Systemic antifungal therapy with fluconazole resolved the initial infection and a subsequent recurrence.

Eye injuries in athletics and recreation.

Sports-related eye injuries represent a significant eye health hazard worldwide. In the USA, it is estimated that eye injuries from sports account for more than 100,000 physician visits per year at the cost of greater than $175 million. The sports responsible for the greatest number of injuries are baseball, ice hockey, and racquet sports. In the USA there are over 189 million participants in these sports with a disproportionate number (one-third) of injuries involving the pediatric population. The most common injuries are abrasions and contusions, followed by more serious injuries, including hyphema. Substantial reduction in the incidence of eye injuries through prevention has been demonstrated in the sport of hockey which can serve as a model for other sports. Specific criteria for protective eyewear must be developed. Polycarbonate plastic lenses and frames which are sturdy and impact resistant provide optimal protection. Lensless goggles, street wear and spectacle correction glasses do not provide adequate eye protection. The ophthalmologist's role in preventing sports-related eye injuries includes addressing particular sports participants needs, identifying one-eyed athletes, and informing patients of the need for protective eyewear.

Unusual leiomyomatous hamartoma of the hard palate: a case report.

Harmartomas of the head and neck are common lesions, often taking the form of melanocytic nevi or vascular malformations such as hemangiomas and lymphangiomas. Hamartomas composed of other tissue types are much rarer and within the oral cavity are usually located on the tongue near the foramen cecum or on the anterior hard palate near the incisive papilla. Although most occur as isolated phenomena, a small number may be associated with other local developmental defects or with a syndrome complex. A normal 5-year-old girl had a 1 cm soft sessile swelling in the vault of the hard palate on the left side. Histopathologic examination showed bundles of smooth muscle embedded in fibrovascular stroma and accompanied by abundant mature fat and a small amount of salivary tissue. The features were regarded as those of a leiomyomatous hamartoma and could be distinguished from a smooth-muscle tumor, teratoma, and benign mesenchymoma by virtue of the clinical and histopathologic features. No recurrence has been seen after excision.

Detection of human papilloma virus DNA sequences in oral squamous cell papillomas by the polymerase chain reaction.

Nineteen clinically diagnosed, and histologically confirmed oral squamous cell papillomas were analyzed for the presence of human papilloma virus DNA sequence by the highly sensitive polymerase chain reaction technique, followed by dot blot hybridization of the polymerase chain reaction product with digoxigenin-labeled, type-specific oligonucleotide probes for human papilloma virus DNA types 6, 11, 16, and 18. Human papilloma virus DNA types 6 and 11 were identified in 68% of these oral lesions, which raises the possibility of an etiologic role for human papilloma virus in the pathogenesis of oral squamous cell papillomas.