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).

Higher HTLV-1c proviral loads are associated with blood stream infections in an Indigenous Australian population.

BACKGROUND: An association between blood stream infections (BSI) and HTLV-1 seropositivity in Indigenous Australians might result from HTLV-1 mediated inflammation and parasite coinfections that provide portals of entry for bacteria. OBJECTIVES: To determine whether BSI risk increases with HTLV-1c proviral load (PVL) and to identify the pathogens responsible in the context of HTLV-1 related conditions. STUDY DESIGN: Indigenous adults admitted to Alice Springs Hospital, central Australia, were recruited as cases or controls according to whether they had a BSI. Clinical data were extracted from case notes and the hospital pathology database. HTLV-1 serology and PVL assays were then performed and risk factors for BSI were determined for HTLV-1 infected subjects. RESULTS: Risk factors were compared between 44 cases and 30 controls who were HTLV-1 Western blot positive. In a multivariable model, high HTLV-1c PVL was predictive of BSI during the study period (OR, 9.10; 95% CI, 2.40-34.4). Median (IQR) HTLV-1c PVL (copies per 100 PBL) was 39-fold higher for patients recording any BSI (0.116 (0.009, 0.277)) relative to those who had no BSI (0.003 (0.000, 0.067))(p=0.0007). Mean (SD) PVL for subjects with no BSI (n=27), 1 BSI (n=37) and ≥2 BSI (n=10) during the study period were 0.120 (0.301), 0.271 (0.622) and 0.500 (0.654) copies per 100 PBL, respectively (p=0.0007). Five BSI were associated with possible complications of HTLV-1; strongyloidiasis (3), infective dermatitis (1), HTLV-1 associated bronchiectasis (1). CONCLUSIONS: Higher HTLV-1c PVL predicts BSI risk; however; most BSI were not associated with recognised complications of HTLV-1 infection.

Higher human T-lymphotropic virus type 1 subtype C proviral loads are associated with bronchiectasis in indigenous australians: results of a case-control study.

BACKGROUND: We previously suggested that infection with the human T-lymphotropic virus type 1 (HTLV-1) subtype C is associated with bronchiectasis among Indigenous Australians. Bronchiectasis might therefore result from an HTLV-1-mediated inflammatory process that is typically associated with a high HTLV-1 proviral load (PVL). Human T-lymphotropic virus type 1 PVL have not been reported for Indigenous Australians. METHODS: Thirty-six Indigenous adults admitted with bronchiectasis from June 1, 2008, to December 31, 2009 were prospectively recruited and matched by age, sex, and ethno-geographic origin to 36 controls. Case notes and chest high-resolution computed tomographs were reviewed, and pulmonary injury scores were calculated. A PVL assay for the HTLV-1c subtype that infects Indigenous Australians was developed and applied to this study. Clinical, radiological, and virological parameters were compared between groups and according to HTLV-1 serostatus. RESULTS: Human T-lymphotropic virus type 1 infection was the main predictor of bronchiectasis in a multivariable model (adjusted risk ratio [aRR], 1.84; 95% confidence interval [CI], 1.19-2.84; P = .006). Moreover, the median HTLV-1c PVL (interquartile range) for cases was >100-fold that of controls (cases, 0.319 [0.007, 0.749]; controls, 0.003 [0.000, 0.051] per 100 peripheral blood lymphocytes; P = .007), and HTLV-1c PVL were closely correlated with radiologically determined pulmonary injury scores (Spearman's rho = 0.7457; P = .0000). Other predictors of bronchiectasis were positive Strongyloides serology (aRR, 1.69; 95% CI, 1.13-2.53) and childhood skin infections (aRR, 1.62; 95% CI, 1.07-2.44). Bronchiectasis was the major predictor of death (aRR, 2.71; 95% CI, 1.36-5.39; P = .004). CONCLUSIONS: These data strongly support an etiological association between HTLV-1 infection and bronchiectasis in a socially disadvantaged population at risk of recurrent lower respiratory tract infections.

Non-communicable diseases, infection and survival in a retrospective cohort of Indigenous and non-Indigenous adults in central Australia.

OBJECTIVES: We hypothesise that rising prevalence rates of non-communicable diseases (NCDs) increase infection risk and worsen outcomes among socially disadvantaged Indigenous Australians undergoing a rapid epidemiological transition. DESIGN: Available pathology, imaging and discharge morbidity codes were retrospectively reviewed for a period of 5 years prior to admission with a bloodstream infection (BSI), 1 January 2003 to 30 June 2007. PARTICIPANTS: 558 Indigenous and 55 non-Indigenous community residents of central Australia. OUTCOME MEASURES: The effects of NCDs on risk of infection and death were determined after stratifying by ethnicity. RESULTS: The mean annual BSI incidence rates were far higher among Indigenous residents (Indigenous, 937/100 000; non-Indigenous, 64/100 000 person-years; IRR=14.6; 95% CI 14.61 to 14.65, p<0.001). Indigenous patients were also more likely to have previous bacterial infections (68.7% vs 34.6%; respectively, p<0.001), diabetes (44.3% vs 20%; p<0.001), harmful alcohol consumption (37% vs 12.7%; p<0.001) and other communicable diseases (human T-lymphotropic virus type 1, 45.2%; strongyloidiasis, 36.1%; hepatitis B virus, 12.9%). Among Indigenous patients, diabetes increased the odds of current Staphylococcus aureus BSI (OR=1.6, 95% CI 1.0 to 2.5) and prior skin infections (adjusted OR=2.1, 95% CI 1.4 to 3.3). Harmful alcohol consumption increased the odds of current Streptococcus pneumoniae BSI (OR=1.57, 95% CI 1.02 to 2.40) and of previous BSI (OR=1.7, 95% CI 1.1 to 2.5), skin infection (OR=1.7, 95% CI 1.1 to 2.6) or pneumonia (OR=4.3, 95% CI 2.8 to 6.7). Twenty-six per cent of Indigenous patients died at a mean (SD) age of 47±15 years. Complications of diabetes and harmful alcohol consumption predicted 28-day mortality (non-rheumatic heart disease, HR=2.9; 95% CI 1.4 to 6.2; chronic renal failure, HR=2.6, 95%CI 1.0 to 6.5; chronic liver disease, HR=3.3, 95% CI 1.6 to 6.7). CONCLUSIONS: In a socially disadvantaged population undergoing a rapid epidemiological transition, NCDs are associated with an increased risk of infection and BSI-related mortality. Complex interactions between communicable diseases and NCDs demand an integrated approach to management, which must include the empowerment of affected populations to promote behavioural change.

Presacral carcinoid tumour arising in a tailgut cyst--a case report.

Primary carcinoid tumours of the presacral region are extremely infrequent with just a handful of such cases reported in literature. Tailgut cysts(retrorectal cystic hamartoma) are also very uncommon lesions which are usually identified in adult life. They are developmental abnormalities and consist of multiloculated cysts lined by squamous, transitional or glandular epithelium. Malignant transformation within tailgut cysts is rare; the tumours which arise include carcinoid tumours and adenocarcinomas. We report the unusual occurrence of a carcinoid tumour developing within a tailgut cyst.