Predictability of Recurrence using Immunohistochemistry to delineate Surgical Margins in mucosal Head and Neck Squamous Cell Carcinoma (PRISM-HNSCC): study protocol for a prospective, observational and bilateral study in Australia and India.

OBJECTIVES: Treatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates of recurrence. Incomplete surgical removal of the tumour, attributed to lack of reliable methods to delineate the surgical margins, is a major cause of disease recurrence. The predictability of recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM) in mucosal HNSCC study aims to redefine margin status by identifying the true extent of the tumour at the molecular level by performing IHC with molecular markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on the surgical margins and test the use of Lugol's iodine and fluorescence visualisation prior to the wide local excision. This article describes the study protocol at its pre - results stage. METHODS AND ANALYSIS: PRISM-HNSCC is a bilateral observational research being conducted in Darwin, Australia and Vellore, India. Individuals diagnosed with HNSCC will undergo the routine wide local excision of the tumour followed by histopathological assessment. Tumours with clear surgical margins that satisfy the exclusion criteria will be selected for further staining of the margins with eIF4E and p53 antibodies. Results of IHC staining will be correlated with recurrences in an attempt to predict the risk of disease recurrence. Patients in Darwin will undergo intraoperative staining of the lesion with Lugol's iodine and fluorescence visualisation to delineate the excision margins while patients in Vellore will not undertake these tests. The outcomes will be analysed. ETHICS AND DISSEMINATION: The PRISM-HNSCC study was approved by the institutional ethics committees in Darwin (Human Research Ethics Committee 13-2036) and Vellore (Institutional Review Board Min. no. 8967). Outcomes will be disseminated through publications in academic journals and presentations at educational meetings and conferences. It will be presented as dissertation at the Charles Darwin University. We will communicate the study results to both participating sites. Participating sites will communicate results with patients who have indicated an interest in knowing the results. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12616000715471).

Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma.

Molecular markers can be used to identify residual cancer at the surgical margins of head and neck squamous cell carcinoma (HNSCC) and assist in evaluating the complete resection of the tumour. The purpose of the present study was to investigate the expression levels of prognostic molecular markers at the histological tumour free surgical margins. In the present clinical retrospective study, 24/48 patients were selected with negative surgical margins for further analysis with immunohistochemical staining. Contingency tables and Fisher's exact tests were used to investigate the association between the expression levels of p53 and eukaryotic translation imitation factor 4E (eIF4E) with the clinical outcomes for patients with HNSCC. The expression levels of p53 and eIF4E were 54.2 and 87.5%, respectively, in the surgical margins of patients with HNSCC. A total of 3/7 patients with recurrent cancer (42.8%) were identified with p53-positive margins, and 6 (85.7%) patients exhibited recurrence with eIF4e-positive margins. No statistically significant differences were identified for the recurrence risk between the overexpression of p53 and eIF4E in the surgical margins (P=0.88 and P=0.99, respectively). The eIF4E marker appears to be a more marked prognosticator compared with p53, as overexpression of eIF4E was identified in the margins of 6/7 patients with local recurrence.

Epidemiology, etiology, and motivation of alcohol misuse among Australian Aboriginal and Torres Strait Islanders of the Northern Territory: a descriptive review.

The per capita alcohol consumption of the Northern Territory, Australia, is second highest in the world, estimated 15.1 liters of pure alcohol per year. Alcohol abuse is a major public health concern among Aboriginal and Torres Strait Islander people in Australia. The Aboriginal and Torres Strait Islanders in the Northern Territory consume approximately 16.9 liters of pure alcohol per year. This descriptive review is based on current published and grey literature in the context of high risk alcohol use, with a special focus on the epidemiological, etiological, and social factors, to predict alcohol misuse among the Australian Aboriginal and Torres Strait Islanders in Northern Territory. The methodology involved a descriptive search on PubMed, Northern Territory government reports, health databases, and Web sites with an emphasis on the etiology and epidemiology of high-risk alcohol consumption among the Australian Aboriginal and Torres Strait Islanders of the Northern Territory. This review has its own limitations because it does not rely on systematic review methodologies. However, it presents real data on the motives for binge drinking and alcohol-related violent assaults of this vulnerable population. Alcohol abuse and alcohol-related harms are considerably high among the rural and remote communities where additional research is needed. High-risk alcohol misuse within Australian Aboriginal and Torres Strait Islanders communities often leads to a series of physical and social consequences. This review highlights the need for culturally appropriate intervention approaches focusing on alcohol misuse among the Aboriginal and Torres Strait Islanders population of the Northern Territory.

Trends in incidence of head and neck cancer in the northern territory, Australia, between 2007 and 2010.

Incidence trends of head and neck cancer (HNC) have implications for screening strategies, disease management, guiding health policy making, and are needed to further oral cancer research. This paper aims to describe trends in age-adjusted HNC incidence rates focusing on changes across calendar period between 2007 and 2010 in Australian Northern Territory. Age-adjusted incidence rates of HNC were calculated for 2007- 2010 using Northern Territory population based data assembled by Department of Health, Northern Territory Government of Australia. Changes in the HNC rate ratio (RR) and Estimated Annual Percentage Change (EAPC) between 2007-2008, 2008-2009 and 2009-2010 were calculated. A total of 171 HNC patients were recorded by the Northern Territory Department of Health during the time period between 2007 and 2010, out of which, 135 were males (78.9% of male HNC patients) and 36 were females (21.1% of female HNC patients). In conclusion, HNC incidence rate has decreased in the Northern Territory Australian males but remains unchanged in Australian females. High incidences of HNC may be associated with the high smoking rate and high alcohol consumption in the Northern Territory. Continued monitoring of trends in HNC incidence rates is crucial to inform Northern Territory based cancer prevention strategies.

The risk factors of head and neck cancer and their general patterns in Australia: a descriptive review and update.

The purpose of this article is to provide a descriptive review of risk factors of head and neck cancer (HNC), with particular interest in their general patterns in Australia. All these risk factors are deeply perplexing, with socioeconomic, cultural, and geographic variables. We reviewed articles from PubMed, MEDLINE, and Google Scholar by using keywords such as risk factors, alcohol, tobacco, human papilloma virus (HPV), environmental risk factors, and other risk factors. We selected relevant articles after they completely fit into the inclusion criteria for this review. Previous reports highlight that smoking tobacco, consuming alcohol, and HPV infection are the major risk factors for HNC. Geographical variations in incidence rates are indicative of differences in the prevalence of risk factors among countries. HNC could be prevented by reducing the prevalence of established risk factors.

Alcohol-Related Violence among the Australian Aboriginal and Torres Strait Islanders of the Northern Territory: Prioritizing an Agenda for Prevention-Narrative Review Article.

Alcohol - related violence among Australian Aboriginal and Torres Strait Islanders (also called as "Indigenous") is a major public health concern in Northern Territory of Australia. There is dearth of epidemiological data that link three contributing epidemics: alcohol misuse, violence, and trauma in the Northern Territory. In this review, we aimed to concentrate on how these epidemics intersect among the Indigenous people in the Northern Territory. In our descriptive review, we have searched published papers, publicly available government and health department reports web sites reporting relevant data on these three risk factors in the Northern Territory. The high rate of family and domestic violence and assaults in the Australian Territory indicates an increased correlation with high risk alcohol use compared to unintentional injuries. Heavy drinking pattern and harmful use of alcohol among Indigenous people are more likely to be associated with the incidence of violent assaults and physical injuries in the Northern Territory. We are trying to emphasize our understanding of co-occurring risk factors on the alcohol - violence relationship and urging a need for interventional approaches to reduce the public health issues in the Northern Territory.

Incidence and mortality from mucosal head and neck cancers amongst Australian states and territories: what it means for the northern territory.

Mucosal head and neck cancers are squamous cell carcinomas that develop in the upper-aero digestive epithelium. Together they constitute the sixth most common cancer with an estimated 900,000 new cases and 350,000 deaths each year reported worldwide. The risk factors are tobacco, alcohol and human papillomavirus (HPV). Our research team initially reported a high incidence rate of HNC in the indigenous population of the Northern Territory. Mortality rates also vary in the Australian States and Territories, with particularly high mortality observed in the Northern Territory. There is a paucity of incidence studies of HNC for the Australian States and Territories. Therefore this review primarily focuses on variation in incidence and mortality iacross the country and highlights specifically the high incidence and mortality in the Northern Territory. Attention is also given to sex-specific incidence and mortality rates.

An Australian retrospective study to evaluate the prognostic role of p53 and eIF4E cancer markers in patients with head and neck squamous cell carcinoma (HNSCC): study protocol.

Complete surgical resection of the primary tumour is a crucial predictive step for head and neck squamous cell carcinoma (HNSCC), because incomplete resection may lead to increase in the recurrence rate. Molecular cancer markers have been investigated as potential predictors of prognosis marker, to identify patients who are at high risk of local recurrence. This retrospective study aimed to determine the prognostic correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival. Forty eight HNSCC patients were selected between 2006 and 2009 diagnosed at the Royal Darwin Hospital, Darwin, Northern Territory, Australia. Out of 48, only those 24 with negative surgical margins with hematoxylin and eosin (HandE) were chosen for further analysis. A total of 77 surgical margins were obtained and subsequently analysed by immunohistochemical (IHC) staining with monoclonal p53 and polyclonal eIF4E antibodies. Contingency table and χ2-test were used to investigate the correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival of the HNSCC patients. The follow up period was 74 months (range 1-74 months). The Kaplan-Meier method was used to generate recurrence and survival curves. This is a first retrospective study of Northern Territory patients, including Indigenous and non-Indigenous Australians. Molecular study of surgical margins could help to identify patients with and without clear margins after surgery and help in choice of the most appropriate adjuvant treatment for HNSCC patients.

Prevention of Alcohol-Related Crime and Trauma (PACT): brief interventions in routine care pathway - a study protocol.

BACKGROUND: Globally, alcohol-related injuries cause millions of deaths and huge economic loss each year . The incidence of facial (jawbone) fractures in the Northern Territory of Australia is second only to Greenland, due to a strong involvement of alcohol in its aetiology, and high levels of alcohol consumption. The highest incidences of alcohol-related trauma in the Territory are observed amongst patients in the Maxillofacial Surgery Unit of the Royal Darwin Hospital. Accordingly, this project aims to introduce screening and brief interventions into this unit, with the aims of changing health service provider practice, improving access to care, and improving patient outcomes. METHODS: Establishment of Project Governance: The project governance team includes a project manager, project leader, an Indigenous Reference Group (IRG) and an Expert Reference Group (ERG).Development of a best practice pathway: PACT project researchers collaborate with clinical staff to develop a best practice pathway suited to the setting of the surgical unit. The pathway provides clear guidelines for screening, assessment, intervention and referral. IMPLEMENTATION: The developed pathway is introduced to the unit through staff training workshops and associate resources and adapted in response to staff feedback. EVALUATION: File audits, post workshop questionnaires and semi-structured interviews are administered. DISCUSSION: This project allows direct transfer of research findings into clinical practice and can inform future hospital-based injury prevention strategies.

Study protocol: Screening and Treatment of Alcohol-Related Trauma (START) - a randomised controlled trial.

BACKGROUND: The incidence of mandibular fractures in the Northern Territory of Australia is very high, especially among Indigenous people. Alcohol intoxication is implicated in the majority of facial injuries, and substance use is therefore an important target for secondary prevention. The current study tests the efficacy of a brief therapy, Motivational Care Planning, in improving wellbeing and substance misuse in youth and adults hospitalised with alcohol-related facial trauma. METHODS AND DESIGN: The study is a randomised controlled trial with 6 months of follow-up, to examine the effectiveness of a brief and culturally adapted intervention in improving outcomes for trauma patients with at-risk drinking admitted to the Royal Darwin Hospital maxillofacial surgery unit. Potential participants are identified using AUDIT-C questionnaire. Eligible participants are randomised to either Motivational Care Planning (MCP) or Treatment as Usual (TAU). The outcome measures will include quantity and frequency of alcohol and other substance use by Timeline Followback. The recruitment target is 154 participants, which with 20% dropout, is hoped to provide 124 people receiving treatment and follow-up. DISCUSSION: This project introduces screening and brief interventions for high-risk drinkers admitted to the hospital with facial trauma. It introduces a practical approach to integrating brief interventions in the hospital setting, and has potential to demonstrate significant benefits for at-risk drinkers with facial trauma. TRIAL REGISTRATION: The trial has been registered in Australian New Zealand Clinical Trials Registry (ANZCTR) and Trial Registration: ACTRN12611000135910.

High risk alcohol-related trauma among the Aboriginal and Torres Strait Islanders in the Northern Territory.

High risk drinking is linked with high rates of physical harm. The reported incidence of alcohol - related trauma among Aboriginal and Torres Strait Islander people in the Northern Territory is the highest in the world. Facial fractures are common among young Aboriginal and Torres Strait Islanders. They are often linked with misuse of alcohol in the Northern Territory and are frequently secondary to assault. This review focuses on alcohol-related trauma in the Territory and draws attention to an urgent need for preventative health approach to address this critical issue.

Metastatic prostate cancer mimicking primary osteosarcoma of the jaw: an infrequent clinical case.

Prostate cancer metastasizing to the mandible is a rare occurrence. This case describes a patient whose presenting symptom was a painless swelling of the left mandible. Radiological investigation demonstrated a lesion within the left mandibular ramus, and subsequent biopsy confirmed the diagnosis of metastatic prostate cancer.