A Clinical, Radiological and Histopathological Review of 74 Ossifying Fibromas.

BACKGROUND: Ossifying fibroma (OF) is a fibro-osseous lesion of the jaws and craniofacial bones. Accurate diagnosis can be challenging due to significant overlap of clinicopathological features. This study aimed to evaluate the clinical, radiological and histological features that can aid in diagnosis and identify characteristics that allow categorisation into the three subtypes: juvenile trabecular, psammomatoid and cemento-ossifying OF. METHODS: A total of 74 cases of OF were systematically reviewed for their principle features. Of these, 46 cases were evaluated for their radiographic features including size, location and relationship to the teeth. Histological assessment and stereological point counting were performed in 69 cases to assess the pattern, type and proportion of calcification, the nature of the stroma, the border of the lesion and the presence of secondary changes. Fisher's exact test and Chi-squared tests were used to determine associations between clinicopathological parameters and maxillary, mandibular, odontogenic, non-odontogenic and psammomatoid or trabecular lesions. RESULTS: OF showed a female predilection (F: M; 2:1) and a slight bimodal age distribution with peaks in the second (23%) and fourth decades (27%) (Mean age: 32.4 years). 83% of cases presented as an intra-oral swelling, with the mandible being the most common site (73%). Histologically, a range of morphological patterns were seen, with 50% of cases showing mixed trabecular and psammomatoid features. However, there were no significant differences between the variants of OF in terms of age, gender or histological features. CONCLUSION: Histological features of OF cannot be used to differentiate between the subtypes.

Do we have a robust method for preoperative tumour depth assessment for oral cavity tumours with clinically negative necks?

Tumour depth is an important prognostic factor in head and neck cancer and has recently been included in the eighth edition of the Union for International Cancer Control TNM classification of malignant tumours for oral squamous cell carcinoma (OSCC). It is important to appraise the accuracy of depth assessments; however, there is little current evidence in the literature. Accurate depth assessment is particularly pertinent in cT1-T2N0 OSCC where it may influence neck management. A retrospective study was performed at two tertiary referral centres, in which surgically treated patients with cT1-T4N0 OSCC were audited. Preoperative tumour depth assessments from multimodality radiological staging scans were compared with the final histopathological depth. The predictive accuracy of intraoral ultrasound (IOUS), computed tomography (CT), and magnetic resonance imaging (MRI) for tumour depth was evaluated. Accuracy to within 3mm of the histopathological depth was seen in 56.7% of MRI scans and 57.1% of CT scans. IOUS appeared to have superior prediction, with 78.2% of measurements within 3mm. Over one third of CT and MRI imaging failed to detect a lesion; IOUS scans detected the lesions in all of these case. In conclusion, the reliability of preoperative imaging assessment of tumour depth should be considered when recommending treatment.

Case-mix adjustment in audit of length of hospital stay in patients operated on for cancer of the head and neck.

Patients treated surgically for squamous cell carcinoma (SCC) of the head and neck form a heterogeneous group, and it is difficult to take this variation into account when measuring the quality of care. We have tested the feasibility of mathematical models that allow for the adjustment for case mix when auditing the length of hospital stay as a proxy indicator of the quality of care. We completed a case-note audit of 733 surgical episodes of care for SCC of the head and neck in five cancer networks, and used logistic regression and decision tree analysis to adjust for case mix using pertinent preoperative variables. Risk adjustment models of length of stay included age, alcohol, T classification, performance status, tracheostomy, high-risk status, and complexity of operation. The risk-adjusted length of stay differed significantly between the cancer networks studied (p<0.001). The models performed acceptably for the purpose of audit when this was under 15 days. Length of stay is a measurable outcome that can be used as a benchmark of surgical care. Audits of this after operations for cancer of the head and neck, if reported in national clinical audits, should take case mix into account.

Biopsy of the sentinel lymph node in oral squamous cell carcinoma: analysis of error in 100 consecutive cases.

UK national guidelines in 2016 recommended that sentinel lymph node biopsy should be offered to patients with early oral cancer (T1-T2 N0) in which the primary site can be reconstructed directly. This study describes the pitfalls that can be avoided in the technique of biopsy to improve outcomes. We retrospectively analysed the data from 100 consecutive patients and recorded any adverse events. Lymphatic drainage of tracer failed in two patients as a result of procedural errors. Two patients with invaded nodes developed recurrence after total neck dissection, one after micrometastases had been diagnosed, and the other as a result of extranodal spread that had led to understaging and therefore undertreatment. Two results would not have been mistakenly classified as clear if all the harvested nodes had been analysed histologically according to the protocol. The disease-specific (96%) and disease-free (92%) survival were better than expected for a group of whom a third had stage 3 disease. If all harvested nodes had been analysed by the correct protocol then two of the three nodes wrongly designated clear would have been detected, two deaths potentially avoided, and the false-negative rate would have fallen from 8.3% to 2.7%. We conclude that minor deviations from protocol can result in a detrimental outcome for the patient.

Validating a benchmarking tool for audit of early outcomes after operations for head and neck cancer.

INTRODUCTION In 2013 all UK surgical specialties, with the exception of head and neck surgery, published outcome data adjusted for case mix for indicator operations. This paper reports a pilot study to validate a previously published risk adjustment score on patients from separate UK cancer centres. METHODS A case note audit was performed of 1,075 patients undergoing 1,218 operations for head and neck squamous cell carcinoma under general anaesthesia in 4 surgical centres. A logistic regression equation predicting for all complications, previously validated internally at sites A-C, was tested on a fourth external validation sample (site D, 172 operations) using receiver operating characteristic curves, Hosmer-Lemeshow goodness of fit analysis and Brier scores. RESULTS Thirty-day complication rates varied widely (34-51%) between the centres. The predictive score allowed imperfect risk adjustment (area under the curve: 0.70), with Hosmer-Lemeshow analysis suggesting good calibration. The Brier score changed from 0.19 for sites A-C to 0.23 when site D was also included, suggesting poor accuracy overall. CONCLUSIONS Marked differences in operative risk and patient case mix captured by the risk adjustment score do not explain all the differences in observed outcomes. Further investigation with different methods is recommended to improve modelling of risk. Morbidity is common, and usually has a major impact on patient recovery, ward occupancy, hospital finances and patient perception of quality of care. We hope comparative audit will highlight good performance and challenge underperformance where it exists.

The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast.

Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are regulated during the cell cycle. This pattern of localization and regulation is similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2 protein. Because aurora2 has been implicated in oncogenesis, defects in kinetochore function may contribute to genetic instability in human tumors.

Regulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase Glc7p.

We have investigated the role of protein phosphorylation in regulation of Saccharomyces cerevisiae kinetochores. By use of phosphatase inhibitors and a type 1 protein phosphatase mutant (glc7-10), we show that the microtubule binding activity, but not the centromeric DNA-binding activity, of the kinetochore complex is regulated by a balance between a protein kinase and the type 1 protein phosphatase (PP1) encoded by the GLC7 gene. glc7-10 mutant cells exhibit low kinetochore-microtubule binding activity in vitro and a high frequency of chromosome loss in vivo. Specifically, the Ndc10p component of the centromere DNA-binding CBF3 complex is altered by the glc7-10 mutation; Ndc10p is hyperphosphorylated in glc7-10 extracts. Furthermore, addition of recombinant Ndc10p reconstitutes the microtubule-binding activity of a glc7-10 extract to wild-type levels. Finally, the glc7-10-induced mitotic arrest is abolished in spindle checkpoint mutants, suggesting that defects in kinetochore-microtubule interactions caused by hyperphosphorylation of kinetochore proteins activate the spindle checkpoint.