DNA damage marker phosphorylated histone H2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity.

AIMS: To evaluate the relationships between immunohistochemical markers related to cellular senescence, cell proliferation and histological grade of epithelial dysplasia (OD) of the oral cavity. In addition, the predictive value of these markers for progression of OD was assessed. METHODS AND RESULTS: Retrospective immunohistochemical analyses were performed on 86 formalin-fixed paraffin-embedded specimens of OD and oral squamous cell carcinoma (OSCC) for Ki67, phosphorylated histone H2AX (γH2AX), p53, p16, trimethyl-histone H3 (Lys9) (H3K9me3) and cyclin D1 (CycD1). Three separate areas representing the highest severity of OD on each slide were annotated digitally by two independent pathologists. Mean automated histoscores of the selected markers were generated and compared to that of age-matched healthy controls (n = 24). Follow-up data of OD were retrieved and anonymized by a clinical team member and linked using unique participant identifiers. The median follow-up was 10.9 years (interquartile range: 10.1-11.5). Ki67 (P < 0.0001), γH2AX (P = 0.03) and p53 (P = 0.04) were increased significantly with higher histological grade of OD. γH2AX (P = 0.03), but not histological grade of OD (P = 0.73), was associated prospectively with disease progression. Using the median histoscore for γH2AX (median histoscore = 17) as a cut-off, histoscore ≥17 was associated with an increased risk of disease progression [hazard ratio (HR) = 3.15, 95% confidence interval (CI): 1.41-7.39, P = 0.0064]. CONCLUSIONS: Although proliferation marker Ki67, DNA damage/checkpoint markers γH2AX and p53 were increased in higher grade of OD, only γH2AX was predictive of disease progression. These observations may reflect the role of DNA replicative stress in the transformation from OD to OSCC. Larger studies should evaluate whether γH2AX can be used as a predictive marker of OD.

A case series of interventions and outcomes in patients with laryngeal squamous cell cancer.

OBJECTIVE: The larynx is the second most prevalent subsite for head and neck cancer. Over half of head and neck cancer patients present with advanced disease. We report our regional practices for palliative intent laryngeal squamous cell cancer (SCC). METHODS: Retrospective analysis of patients with laryngeal SCC treated with palliative intent, discussed at the regional head and neck multidisciplinary team meeting from July 2010 to June 2016. RESULTS: A total of 65 patients were included, of whom 45 per cent had potentially curable disease but were not fit for curative treatment. Nine patients (14 per cent) underwent tracheostomy, with mean survival and hospital stay of 278 and 48 days, respectively. Four patients (6 per cent) underwent debulking surgery with mean survival and hospital stay of 214 and 1 days, respectively. CONCLUSION: All palliative treatment measures offered to patients can have an impact on survival and quality of life. Patients should be at the centre of the decision-making process and counselled on the potential impact of interventions.

Applying the British Association of Oral and Maxillofacial Surgeons quality outcomes metrics to a regional Australian oncology and reconstructive service: benchmarking the data to audit clinical outcomes in emerging, regional, and small-volume centres.

The traditional model of centralisation of care, whilst having many advantages, also requires adaptation and upscaling to meet the requirements of both regional areas and the increasing urban sprawl. However, to ensure comparable outcomes with current major centres, this transition, when required, must be delivered in a safe and effective manner. Our project, which utilised the British Association of Oral and Maxillofacial Surgeons (BAOMS) recently published outcome data from the Quality and Outcomes in Oral and Maxillofacial Surgery (QOMS) project to benchmark data prospectively collected from a small-volume, emerging centre in Northern Queensland, was the first of its kind in terms of validation studies. As expected, the small volume of our centre impacted the ability to derive powerful statistical models and comparators, an intrinsic limitation for small-volume centres whilst they are developing services. However, during this evolution project, the use of comparison metrics allowed for the detection of alert and alarm levels, which are invaluable to ensure patient safety and quality of outcome.Our paper demonstrated that, irrespective of size or volume, the utilisation of quality assurance metrics (national or international) provides for the safe and transparent upscaling of head and neck services in emerging, regional, and small-volume centres.

Risk prediction of complicated course in patients undergoing major head and neck surgery with free flap reconstruction.

The British Association of Oral and Maxillofacial Surgeons (BAOMS) Quality and Outcomes in Oral and Maxillofacial Surgery (QOMS) reconstructive audit aims to provide surgical teams with risk adjusted comparative performance data. The goal is to enable surgeons to optimise surgical pathways. Risk adjustment requires that data on appropriate predictive variables are collected. This study looked at variables predicting major complications and flap failure in a single institution with the aim of determining whether the QOMS dataset adequately captures the appropriate data points. A prospective database of head and neck flap procedures and associated postoperative complications has been maintained in the maxillofacial surgery department since August 2009 up to August 2022 (n=1327). A total of 25 putative risk variables were extracted from the health records for each patient. The outcomes of interest were total flap failure and major complications. Independent predictors of flap failure were recipient site (sinonasal/anterior skull base), previous major surgery, previous major surgery and radiotherapy, and flap selection. For major complications ACE-27 comorbidity score, flap type, use of tracheostomy, elevated preoperative plasma C-reactive protein (CRP) and flap selection were independently predictive. Apart from preoperative activated innate immunity all relevant risk stratification variables identified in this study form part of the QOMS dataset. QOMS is therefore likely to adequately risk stratify patients based upon currently collected variables.

The functional intraoral Glasgow scale in floor of mouth carcinoma: longitudinal assessment of 62 consecutive patients.

The functional integrity of the floor of the mouth (FOM) is essential in maintaining tongue mobility, deglutition, and control and disposal of saliva. The present study focused on reporting oral function using functional intraoral Glasgow scale (FIGS) in patients who had surgical ablation and reconstruction of FOM carcinoma with or without chemo-radiotherapy. The study included patients who had surgical treatment of floor of mouth cancer in two regional head and neck units in Glasgow, UK between January 2006 and August 2007. Patients were assessed using FIGS before surgery, 2 months, 6 months and 1 year after surgery. It is a five-point scale self-questionnaire to allow patients to self-assess speech, chewing and swallowing. The maximum total score is 15 points. The influence of socio-demographic parameters, tumour characteristics and surgical parameters was addressed in the study. A total of 62 consecutive patients were included in the study; 41 (66.1 %) were males and 21 (33.9 %) were females. The patients' mean age at the time of diagnosis was 60.6 years. Fifty (80.6 %) patients had unilateral origin of FOM tumours and 10 (19.4 %) had bilateral origin. Peroral approach was the most common approach used in 35 (56.4 %) patients. The mean preoperative FIGS score was 14. Two months after surgery, it droped to 9.4 then started to increase gradually thereafter and recorded 10.1 at 6 months and 11 at 1 year. Unilateral FOM resection recorded better score than bilateral and lateral FOM tumours than anterior at 1 year postoperatively. Furthermore, direct closure showed better functional outcome than loco-regional and free flaps. The FIGS is a simple and comprehensive way of assessing a patient's functional impairment following surgery in the FOM. Tumour site and size, surgical access, surgical resection and method of reconstruction showed significant influence on oral function following surgical resection. A well-designed rehabilitation programme is required to improve oral function after surgical resection of oral cancer.

Patterns of recurrence in patients undergoing curative treatment for maxillary alveolus squamous cell carcinoma.

The aim of this paper was to examine patterns of recurrence in patients undergoing curative treatment for maxillary alveolus squamous cell carcinoma (MASCC). Clinicopathological data on 41 patients undergoing curative resection for MASCC between February 2006 and May 2020 were retrospectively gathered. Outcomes included local, regional, or distant failure as first site of treatment recurrence. Univariate analysis identified significant clinicopathological variables for type of recurrence. Multivariate regression analysis generated predictive models. Ten of 41 patients developed regional recurrence, and nine manifested contralateral recurrence following ipsilateral neck dissection. In three patients the ipsilateral neck was pN0. Nodal metastasis was predictive of regional recurrence, particularly with extranodal tumour extension (ENE). Multivariate analysis with regional recurrence confirmed that ENE was independently predictive. Nodal disease and ENE in patients with MASCC was found to be predictive of contralateral regional recurrence. Management of the neck in MASCC that extends to the palatal aspect should therefore be considered as midline disease.

Prognostic significance of dysplasia associated with oral squamous cell carcinoma in patients undergoing surgery with curative intent.

The aim of this study was to evaluate the prognostic significance of dysplasia in patients undergoing primary surgery with curative intent in the treatment of oral squamous cell carcinoma (OSCC). This study specifically aimed to demonstrate the effect of dysplasia on local recurrence, disease specific survival (DSS) and overall survival (OS). Data collection for 833 patients with OSCC undergoing treatment for curative intent was undertaken retrospectively for the period of February 2006 to May 2020. Analysis of any association between known clinicopathological prognostic categorical variables with respect to dysplasia was undertaken using the chi squared test. A Kaplan-Meier analysis was performed to demonstrate the impact of dysplasia on DSS and OS, and Cox's proportional-hazards model deployed to obtain hazard ratios associated with dysplasia and the outcomes of interest. Dysplasia was statistically significant in predicting disease specific and overall survival in patients undergoing primary surgery for OSCC (DSS p<0.001, HR 0.577; 95%CI 0.428 to 0.777), OS p<0.001 HR 0.691; 95%CI 0.562 to 0.850) with the absence of dysplasia predicting poorer outcomes. The absence of dysplasia correlated with pathological higher T and N stage, increased categorised depth of tumour invasion, non-cohesive invasive front, lymphovascular invasion, perineural invasion, extranodal extension and increased modified Glasgow Prognostic Score. No significant prognostic relationship was attributable to the presence of dysplasia at a surgical margin. The absence of dysplasia appeared to be a significant independent prognostic indicator for patients with OSCC. The presence or absence of dysplasia may provide a heuristic means of stratifying OSCC primary lesions in terms of disease hostility.

Systemic inflammatory response in predicting outcomes of patients undergoing curative resection for oral squamous cell carcinoma.

This study aimed to evaluate the prognostic significance of the modified Glasgow prognostic score (mGPS), neutrophil:lymphocyte ratio (NLR), and platelet:lymphocyte ratio (PLR) in patients undergoing resection of oral squamous cell carcinoma (OSCC) with curative intent. We also aimed to explore the relation between activated systemic inflammation and adverse tumour characteristics. Between February 2006 and December 2019, data on 825 patients undergoing curative resection of OSCC were retrospectively gathered. Preoperative C-reactive protein and serum albumin levels were obtained to calculate a mGPS. Full blood count parameters were collected to calculate NLR and PLR values. Categorical factors were analysed using the chi squared test. Multivariate regression was performed to identify independent prognostic variables and the predictive value of each model generated. For disease-specific survival (DSS) and overall survival (OS), mGPS (DSS and OS both p<0.001), NLR (DSS and OS both p<0.001) and PLR (DSS and OS both p<0.001) were significant on univariate analysis. Independent predictive variables for DSS included mGPS, clinical node stage, categorised depth of tumour invasion, non-cohesive invasive front, and lymphovascular invasion. The concordance index was acceptable (0.756) for this model. Replacing mGPS with NLR or PLR as a marker of systemic inflammation demonstrated the same preoperative variables as independently predictive for DSS. The concordance index for these models were acceptable (NLR 0.76 and PLR 0.756). The systemic inflammatory response is prognostically significant in patients undergoing curative resection of OSCC. The potential link between an inflammatory tumour microenvironment and activated systemic inflammation merits further investigation.

The relative propensity for regional metastasis in floor of mouth squamous cell carcinoma versus other oral cavity subsites.

There are previous papers suggesting that floor of mouth (FOM) oral squamous cell carcinomas (OSCC) metastasise earlier than other oral cavity subsites. This report further evaluates that hypothesis. Between February 2006 and December 2019, 825 patients underwent curative resection of OSCC. Data on nodal metastases and depth of invasion (DOI) of the primary tumour were collated. The relationship between tumour DOI and likelihood of nodal metastases was examined. A total of 203 patients had a FOM OSCC, 75 of which had nodal metastases. No difference was found in the incidence of, or correlation with DOI, and occurrence of regional metastases when FOM was compared to other OSCC subsites. We conclude that FOM OSCC has a similar regional metastatic propensity as other subsites in the oral cavity.

Patterns of recurrence amongst patients undergoing resection of oral squamous cell carcinoma with curative intent.

This study was aimed to identify key clinicopathological variables that predict recurrence in those undergoing curative resection of oral squamous cell carcinoma (OSCC) with emphasis on initial treatment failure patterns. Between February 2006 to May 2020, clinicopathological data on 833 patients who underwent curative resection of OSCC were gathered. Outcomes of interest included local, regional, distant, and overall recurrence. Univariate analysis was performed to identify significant clinicopathological variables for each recurrence type, and a multivariate regression analysis was utilised to generate predictive models. A total of 187 patients (22.4%) developed recurrent disease; 79 local, 63 regional, and 46 distant. For local recurrence: tumour depth of invasion (DOI) >5--10 mm, tumour DOI >10 mm and modified Glasgow Prognostic Score (mGPS) 2 were independently predictive (c-index 0.708). For regional recurrence: primary OSCC of hard palate/maxilla, pN1, pN3b, and non-cohesive invasive front were independently predictive (c-index 0.738). For distant recurrence: pN1 pN2a, pN2b, pN2c, pN3b, and tumour DOI >10 mm were independently predictive (c-index 0.809). For recurrence at any site; pN1, pN2a, pN2b, pN2c, pN3b, tumour DOI >5-10 mm, tumour DOI >10 mm, mGPS 2, and involved surgical margins were independently predictive (c-index 0.750). Recurrence events after curative treatment for OSCC are relatively predictable on the basis of available clinicopathological characteristics. It seems likely that trials of adjuvant systemic therapy in high-risk OSCC will continue to be designed with emerging therapeutic agents. Trials should focus on those of highest risk of relapse and this study adds clarity to the selection of the correct target population.

Machine learning methods applied to risk adjustment of cumulative sum chart methodology to audit free flap outcomes after head and neck surgery.

We describe a risk adjustment algorithm to benchmark and report free flap failure rates after immediate reconstruction of head and neck defects. A dataset of surgical care episodes for curative surgery for head and neck cancer and immediate reconstruction (n = 1593) was compiled from multiple NHS hospitals (n = 8). The outcome variable was complete flap failure. Classification models using preoperative patient demographic data, operation data, functional status data and tumour stage data, were built. Machine learning processes are described to model free flap failure. Overall complete flap failure was uncommon (4.7%) with a non-statistical difference seen between hospitals. The champion predictive model had acceptable discrimination (AUROC 0.66). This model was used to risk-adjust cumulative sum (CuSUM) charts. The use of CuSUM charts is a viable way to monitor in a 'Live Dashboard' this quality metric as part of the quality outcomes in oral and maxillofacial surgery audit.

Sentinel lymph node biopsy for early oral cancer - accuracy and considerations in patient selection.

Sentinel lymph node biopsy (SLNB) for staging oral squamous cell carcinoma (OSCC) patients presenting with early (T1 and T2 N0) disease in preference to elective neck dissection (END) remains controversial worldwide. A retrospective analysis of 145 patients who underwent sentinel lymph node biopsy for a previously untreated early oral cancer between 2010 and 2020 was performed. The primary outcome measures were predictors of occult metastases, accuracy of SLNB and disease specific plus overall survival. The negative predictive value, the false negative rate, and sensitivity for SLNB were 97%, 7.8%, and 92%, respectively. Depth of invasion (DOI) was a significant predictor of N status, overall survival, and disease specific survival. There was a significant difference in the incidence of the neck node metastasis in patients with DOI <5mm compared to those with DOI >5mm. For tumours >5mm there was a moderate to good correlation between radiological depth on contrast enhanced computed tomography (CECT) and histopathological DOI. Preoperative estimation of DOI may be a useful tool in the counselling of patients in the selection of either SLNB or END for N staging purposes in early OSCC.

Survival in node-positive early oral squamous cell carcinoma: sentinel node biopsy versus elective neck dissection.

Patients undergoing sentinel node biopsy (SLNB) for early oral squamous cell carcinoma (OSCC) who harbour occult metastases (pN+ve) may be at greater risk of mortality due to prolonged overall treatment times than those identified as pN+ve on elective neck dissection (ELND). A retrospective comparative survival analysis was therefore undertaken to test this hypothesis. Patients were identified from the South Glasgow multidisciplinary team (MDT) database. Group 1 comprised 38 patients identified as pN+ve, or who were false negative, on sentinel lymph node biopsy (SLNB). Group 2 comprised 146 patients staged pN+ve on ELND. The groups were compared with the Kaplan Meier method and Cox proportional hazards model. In addition, a matched-pair analysis was performed. A unique and specifically designed algorithm was deployed to optimise the pairings. No difference in disease-specific or overall survival was found between the groups. Patients undergoing SLNB as the initial neck staging modality in early OSCC and are identified as pN+ve do not appear to be at a survival disadvantage compared with those staged with ELND.

The relevance of surgical margins in clinically early oral squamous cell carcinoma.

OBJECTIVES: There is controversy regarding surgical margins in the management of early oral squamous cell carcinoma (OSCC). The main objectives of this study were to assess the: relevance of the margin independent of tumour variables; threshold for a safe margin; relevance of dysplasia at the margin. MATERIALS & METHODS: UK based retrospective multicenter cohort study of patients with previously untreated and clinically early OSCC between 1998 and 2016. All patients had surgery as the primary modality and had surgical staging of the neck. Minimum follow-up was 2 years. Margins were classified as: clear ≥5.0 mm; close 1.0-4.9 mm; involved not cut-through (INC-T) 0.1-0.9 mm; cut-through (C-T) 0 mm. RESULTS: 669 patients were included. After adjusting for tumour variables Cox multivariate regression analysis demonstrated that close margins had similar survival outcomes to clear margins (Hazard Ratio(HR) 0.99 (95%CI 0.50-1.95) for Local Recurrence Free Survival (LRFS); HR 1.08 (95%CI 0.7-1.66) for Disease Free Survival (DFS); HR 0.74 (95%CI 0.44-1.25) for Disease Specific Survival (DSS); HR 0.80 (95%CI 0.58-1.11) for Overall Survival (OS)). C-T margins had significantly worse LRFS (HR 5.01 (95%CI 2.02-12.39)) and DFS (HR 2.58 (95%CI 1.28-5.20)). INC-T margins had significantly worse DFS (HR 1.98 (95% CI 1.01-3.87)). Time dependent receiver operating characteristic curve analysis did not demonstrate a clear margin threshold for LRFS within 24 months (AUC = 0.53 (95%CI 0.41-0.64)). Dysplasia at the margin did not influence LRFS or DFS. CONCLUSION: Only resection margins <1 mm independently affected survival outcomes. This should be considered when making decisions regarding adjuvant treatment.

Vascularized temporoparietal fascial flap for the treatment of a traumatic cerebrospinal fluid fistula in the middle cranial fossa. Technical note.

The temporoparietal fascial flap (TPFF) is a vascularized pedicle flap commonly used in head and neck reconstructions. The authors describe the use of a TPFF in repairing a large traumatic middle cranial fossa CSF fistula via a middle cranial fossa approach. During the 18-month follow-up, the patient had no further CSF leakage or meningitis. The use of a TPFF for the repair of a traumatic CSF fistula has not been described in the literature. The authors recommend the use of a TPFF in treating recurrent or large middle cranial fossa CSF fistulas. The flap provides a well-vascularized thin layer that can be ideal in middle cranial fossa repair, and its proximity to the operation site is perfect as well.

Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer.

BACKGROUND: The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer. METHOD: Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines. RESULTS/CONCLUSION: A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.

One miniplate versus two in the management of mandibular angle fractures: a prospective randomised study.

We compared the use of one miniplate (n=36) with that of two miniplates (n=26) for the treatment of the mandibular angle in a randomised trial. There were no significant differences between the groups in total morbidity (22/36 compared with 14/26) or for individual complications. We conclude that two miniplates seem to confer no extra benefit to patients, but a much larger trial would be required to show this conclusively.

Laryngeal dysplasia: aetiology and molecular biology.

Laryngeal premalignancy is a common clinical concern. While tobacco has long been established as the principal identifiable aetiological factor, the last two decades have seen publications investigating a potential role for gastroesophageal reflux, gastrectomy and human papilloma virus. Furthermore, there have been major advances in our understanding of the molecular biology of cancer and premalignancy. Accompanying this increased understanding, significant efforts have been made to correlate the expression of molecular markers with the clinical course of premalignant laryngeal lesions. This review summarizes current knowledge of the aetiological factors and molecular biology of laryngeal premalignancy. All aetiological factors, including molecular markers, are discussed separately and their possible role in the clinical course of these lesions is discussed.