Associations between environmental exposures in the Middle East Area of Operations and pregnancy outcomes in Australian Defence Force veterans.

Military personnel deployed on operations may encounter a variety of hazards with the capacity to adversely affect reproductive health. This paper investigates the association between self-reported exposure to reproductive toxicants and adverse pregnancy outcomes in Australian Defence Force veterans who deployed to Iraq and Afghanistan during the period 2001-2009. Utilising the Middle East Area of Operations (MEAO) Census Study data set, descriptive analyses of participants' self-reported exposure were compared with the occupational environmental monitoring data taken at their reported deployment location. Univariate analyses assessed the significance of unadjusted associations between self-reported exposures and reproductive outcomes. There is no systematic or consistent relationship between deployment to the MEAO and adverse pregnancy outcomes. Overall, self-reported adverse reproductive outcomes were significantly increased in veterans who deployed to both Afghanistan and Iraq (p = 0.04) compared to those who only deployed to only one of those locations; particularly in women (p = 0.009). Miscarriage was the most likely of these (p = 0.008). These figures would benefit from being confirmed against medical records but are worthy of further study. In this historical cohort study, causal inference cannot be made due to absence of control groups to exclude sources of potential bias. Imprecision in the assessment of environmental hazards in the MEAO and other methodological constraints make it impossible to calculate precise estimates of risk. The results warrant continued investigation, especially when combined with previous findings related to pregnancy outcomes in this population, the importance of reproductive outcomes, and the potential emergence of new hazards.

Cost-effectiveness analysis of imaging surveillance in stage II and III extremity soft tissue sarcoma: an Australian perspective.

BACKGROUND: Surveillance imaging is used to detect local and/or distant recurrence following primary treatment of localised soft tissue sarcoma (STS), however evidence supporting optimal surveillance modality or frequency is lacking. We used prospectively collected sarcoma data to describe current surveillance imaging practice in patients with AJCC stage II and III extremity STS and evaluate its cost-effectiveness. METHODS: From three selected Australian sarcoma referral centres, we identified patients with stage II and III extremity STS treated between 2009 and 2013. Medical records were reviewed to ascertain surveillance imaging practices, including modality, frequency and patient outcomes. A discrete event simulation model was developed and calibrated using clinical data to estimate health service costs and quality adjusted life years (QALYs) associated with alternative surveillance strategies. RESULTS: Of 133 patients treated for stage II and III extremity STS, the majority were followed up with CT chest (86%), most commonly at 3-monthly intervals and 62% of patients had the primary site imaged with MRI at 6-monthly. There was limited use of chest-X-ray. A discrete event simulation model demonstrated that CT chest screening was the most cost effective surveillance strategy, gaining additional QALYs at a mean incremental cost of $30,743. MRI alone and PET-CT alone were not cost-effective, whilst a combined strategy of CT + MRI had an incremental cost per QALY gained of $96,556. CONCLUSIONS: Wide variations were observed in surveillance imaging practices in this high-risk STS cohort. Modelling demonstrated the value of CT chest for distant recurrence surveillance over other forms of imaging in terms of cost and QALYs. Further work is required to evaluate cost-effectiveness in a prospective manner.

A population-based study of soft tissue sarcoma incidence and survival in Australia: An analysis of 26,970 cases.

BACKGROUND: Soft tissue sarcomas (STS) are rare, often fatal tumors, but little is known of the epidemiology and survival in the Australian population. This study aims to provide the first epidemiological analysis of incidence and survival rates of STS in the Australian population. METHODS: A retrospective population-based observational study was conducted between 1982 and 2009 of all patients with a diagnosis of STS using the Australian Institute of Health and Welfare (AIHW) Australian Cancer Database. Incidence rates per 100,000; incidence rate ratios, age-standardized incidence rates, prevalence and incidence rates of subtypes of STS, median, one-year and 5-year survival rates were examined. RESULTS: A total of 26,970 patients were identified. Between 1982 and 2009 STS incidence rates significantly increased from 3.99 [95% CI 3.68-4.32] to 6.12 [95% CI 5.80-6.46] per 100,000 Australian population, with a peak incident rate ratio (IRR) of 1.59 [95% CI 1.51-1.69] (p < 0.0001) in 2001. Median age at diagnosis increased from 58 to 63 years. Incidence rates were stable across all 10-year age cohorts, except for people aged over 70 where it increased. Overall, age-standardized incidence rates increased from 4.70 [95% CI 4.42-5.00] in 1982 to 5.87 [95% CI 5.63-6.11] per 100 000 Australians in 2009. Leiomyosarcoma (20.43%), malignant fibrous histiocytoma (16.14%), and soft tissue tumors/sarcomas, not otherwise specified (10.18%) were the most common STS subtypes. Median survival from diagnosis increased from 5.80 years [95% CI 5.06-6.54] in 1985-1989 cohort to 8.18 years [95% CI 7.54-8.81] in the 2000-2004 cohort (log-rank test p < 0.0001). CONCLUSION: The incidence of STS is increasing in Australia, most noticeably in those aged over 70 years, with a small but statistically significant increase in overall survival rates.

Health-related quality of life, psychosocial functioning, and unmet health needs in patients with sarcoma: A systematic review.

OBJECTIVE: Health-related quality of life (HRQoL), psychosocial distress, and unmet health needs are important patient-reported outcomes (PROs) for patients with sarcoma treated with curative intent. Syntheses of data on these PROs in patients with sarcoma are limited. METHODS: A systematic review of peer-reviewed literature published between 2007 and 2017 was conducted using five databases, guided by the PRISMA and Cochrane reporting guidelines. RESULTS: Of 7240 articles identified, 31 were included in this review. Compared with healthy individuals, patients with sarcoma frequently scored lower in physical and psychological HRQoL domains and experienced higher rates of self-image issues, depression, and suicide. However, outcomes for patients with sarcoma were relatively comparable to those with other malignancies. Anxiety symptoms were more common in the diagnosis phase, while depressive symptoms were more common in the treatment phase. Patients who are older, female, and socially isolated often reported lower HRQoL. As a sarcoma-specific HRQoL instrument is not available, and all studies have used generic instruments, key issues may have been omitted. CONCLUSION: There are few studies reporting data for HRQoL, psychosocial issues, or unmet health needs in this population. A sarcoma-specific HRQoL instrument is needed to accurately describe outcomes in this population. There is a need for further qualitative research to conceptualise the HRQoL issues relevant to this population, against which to map existing HRQoL instruments and guide adaptation or creation of a new instrument.

Patterns of head and neck sarcoma in Australia.

BACKGROUND: Sarcomas affecting the head and neck often require complex management due to the combination of anatomic, aesthetic and oncological considerations. The incidence and patterns of presentation are poorly understood and have not been reviewed in the Australian population. METHOD: This study sourced incidence and demographic data from the National Cancer Registry at the Australian Institute of Health and Welfare for the years 1982-2009 (corresponding to 97.3% of the Australian population). All cases of sarcoma, according to ICD-O-3 classification ((International Classification of Diseases for Oncology, 3rd edition), were assessed. RESULTS: A total of 3911 new cases of sarcoma affecting the head and neck were recorded during the period 1982-2009, including 1383, 2106 and 442 cases arising from skin, soft tissue and bone, respectively. The annual incidence rate of sarcomas affecting the head and neck was 1.59 per 100 000 population. The incidence of head and neck sarcoma rose substantially in older age groups (age 65 years and above) and was most common in male patients (69%). Malignant fibrous histiocytoma (MFH) was the most common pathology. There was an increase in incidence in skin-origin sarcoma in the head and neck, particularly affecting elderly males. CONCLUSION: The incidence of head and neck sarcoma in Australia is higher than that reported for an equivalent European population. The increase in MFH arising from the skin in elderly male patients mirrors the patterns of common cutaneous malignancy, particularly melanoma, suggesting that ultraviolet radiation is an epidemiological factor. Management of head and neck sarcoma is complex and best managed in a specialist multidisciplinary environment.

The ties that bind: what's in a title?

BACKGROUND: Many Australian and New Zealand surgeons use the title 'Mister' rather than 'Doctor', a practice dating back to traditions established over 600 years ago. The Royal Australasian College of Surgeons is currently undergoing a period of critical self-reflection, embodied by its 'Respect' campaign. Active measures to embrace diversity and encourage women into surgery are underway. METHODS: This paper reviews the historical basis to the use of gendered titles and their current use amongst fellows. De-identified demographic data from the college register of active fellows was searched by self-identified title, country or state, and gender. Data were further reviewed by surgical sub-specialty and year of fellowship. RESULTS: The college dataset suggests that there is significant variance in the preference for gendered titles, determined predominantly by geography rather than specialty. The highest use of gendered titles (by male and female surgeons) was in Victoria/Tasmania (58% male, 22% female) and New Zealand (81% male, 17% female). By contrast, only 2% of female surgeons in other states elected a gendered title (Miss/Mrs/Ms). CONCLUSION: Surgery is the only profession that continues to use gendered titles. As the College of Surgeons moves towards greater equity and diversity, consideration should be given to phasing out the use of gendered titles, which serve to divide rather than unite our profession.

Intravenous lobular capillary haemangioma (pyogenic granuloma): A case report and a review of imaging findings as reported in the literature.

INTRODUCTION: Intravenous lobular capillary haemangioma (IVLCH) is a rare benign lesion with minimal published reports containing a description of its appearance at medical imaging. We present the ultrasound and MRI images of a histologically proven IVLCH and provide the first review of the imaging findings reported in the literature. METHODS: The imaging findings of a case of IVLCH are presented. A PubMed search of English language articles was performed from 1966 to October 2016, and all relevant papers were reviewed. Imaging findings from those papers are summarised. RESULTS: Key features on ultrasound are of a well-defined, usually hypoechoic, mass which is highly vascular. The host vein is usually apparent. MRI imaging usually shows T1 signal isointense to muscle and variable T2 signal, either isointense or of high signal relative to the vein. The lesions enhance with gadolinium. CONCLUSION: Intravenous lobular capillary haemangioma has distinctive ultrasound but less consistent MRI features although radiological diagnosis should usually be possible. Review of reported cases shows that a previously described gender bias is incorrect.

Feasibility of spacers to facilitate postoperative radiotherapy for retroperitoneal sarcomas.

INTRODUCTION: The role and timing of postoperative radiotherapy (PORT) in the management of retroperitoneal sarcoma (RPS) remains controversial. METHOD: This is a retrospective cohort review of patients undergoing curative resection for RPS at a single institution between January 2011 and July 2016. Patient selection was through the South Australian Soft Tissue Tumour Multidisciplinary Group (MDT) based at Royal Adelaide Hospital. An individualised approach, including assessment of resectability, histopathological grade and subtype, and radiotherapy considerations, was taken for each patient. Patients offered preoperative radiotherapy or palliation were excluded. A saline-filled spacer was inserted following operative resection. Radiotherapy commenced postoperatively. Patients underwent laparotomy to remove the device approximately 6 weeks post completion of PORT. Primary endpoints were technical feasibility, perioperative morbidity and radiation toxicity. Secondary endpoints were local recurrence (LR), distant recurrence (DR) and death. RESULTS: During the study period, 40 patients with RPS were managed through the MDT. Twelve patients (ages 33-78) underwent PORT utilising spacers. Radiotherapy toxicity was reported in four patients and extensive adhesions observed in another four patients during spacer removal. Median follow-up was 35 months (range 4-60). Seven patients remain alive and disease free. Four patients developed LR, three developed DR. Three patients died; two with DR and one with LR. Two patients with recurrent/progressive disease are alive; one with DR and one with LR. CONCLUSION: Use of intraoperative spacers to facilitate PORT is feasible, with acceptable toxicity following resection of RPS. Patient selection for this approach remains to be determined.

Desmoid Fibromatosis Presenting as Deep Venous Thrombosis: A Case Report and Discussion.

BACKGROUND Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common, serious cardiovascular event. Predisposing factors include genetic disorders, immobility, and underlying malignancy. Soft tissue tumors are by contrast rare, but should be included in the differential etiology of DVT, especially when the patient is young and has few thrombotic risk factors. CASE REPORT We present a 40-year-old patient whose initial diagnosis was spontaneous DVT of the lower leg, treated conventionally. Subsequently, he developed progressive calf swelling, which was diagnosed as multifocal desmoid fibromatosis, a rare and complex soft tissue tumor. CONCLUSIONS DVT is common but soft tissue tumors are rare. The disparity in incidence of these very distinct pathologies may contribute to late diagnosis of occult soft tissue pathology. We discuss the incidence, etiology, pathology, diagnosis, and best management of both desmoid fibromatosis and DVT, which may co-exist in a causative way.

Making cancer visible--Dyes in surgical oncology.

Dyes share an intricate relationship with oncology. Dyes can cause cancer as chemical carcinogens, but can also be harnessed against cancer when used as diagnostic and therapeutic agents. Histopathology, imaging, and newer molecular diagnostics all rely on dyes, and their use in sentinel lymph node biopsies and intra-operative imaging has helped drive a paradigm shift in cancer surgery towards minimally-invasive and organ sparing approaches with enhanced resection accuracy. As therapeutic agents, the cytotoxicity of specific dyes can be employed in direct chemo-ablation or in photodynamic therapy. The same agent can have dual functionalities in cancer detection and treatment, in a novel field known as theranostics. This is facilitated by newer generation dyes conjugated with tumour-targeting probes such as antibodies, and these bio-conjugate agents can also incorporate nanotechnology or radio-isotopes. Further advances will be closely aligned with our increasing understanding of molecular oncology, and will form a new generation of cancer detection and treatment agents that promote precision medicine for cancer. Dyes and their roles have evolved and been reinvented, but they remain relevant as ever. This review explores the fascinating history of dyes, and their place in the state-of-the-art of oncology.

Primary pericardial mesothelioma presenting as multiple pericardial masses on CT.

We present the case of a 67-year-old male who was found to have multiple enhancing pericardial masses on CT imaging for investigation of weight loss and was subsequently diagnosed with primary pericardial mesothelioma. Although rare, pericardial mesothelioma is the most common primary malignancy of the pericardium and should be considered in the differential diagnosis of pericardial effusion, pericardial thickening or discreet pericardial mass. It is important for radiologists to be aware of pericardial mesothelioma as its clinical presentation is non-specific and it may be incidentally noted on radiological studies for investigation of apparently non-related symptoms. The prognosis of primary pericardial mesothelioma is universally poor.

Surgery: no profession for a lady.

There are currently over 700 active female Fellows of the Royal Australasian College of Surgeons, accounting for just less than 10% of the surgical workforce. The first female Fellow of the College was Lillian Violet Cooper, of Queensland, who was admitted to Fellowship on 17 June 1927. Over the following half century, 32 women obtained Fellowships, initially awarded on the basis of experience and clinical practice and then, from 1947, by passing the Fellowship examination. This paper will examine the contribution of some of these early pioneer women, not just as surgeons, but as role models, advocates of women in professional life and champions of equality.

XI-006 induces potent p53-independent apoptosis in Ewing sarcoma.

There is an imperious need for the development of novel therapeutics for the treatment of Ewing sarcoma, the second most prevalent solid bone tumour observed in children and young adolescents. Recently, a 4-nitrobenzofuroxan derivative, XI-006 (NSC207895) was shown to diminish MDM4 promoter activity in breast cancer cell lines. As amplification of MDM4 is frequently observed in sarcomas, this study examined the therapeutic potential of XI-006 for the treatment of Ewing and osteosarcoma. XI-006 treatment of Ewing and osteosarcoma cell lines (n = 11) resulted in rapid and potent apoptosis at low micro-molar concentrations specifically in Ewing sarcoma cell lines (48 hr IC50 0.099-1.61 µM). Unexpectedly, apoptotic response was not dependent on MDM4 mRNA/protein levels or TP53 status. Alkaline/neutral comet and γH2AX immunofluorescence assays revealed that the cytotoxic effects of XI-006 could not be attributed to the induction of DNA damage. RNA expression analysis revealed that the mechanism of action of XI-006 could be accredited to the inhibition of cell division and cycle regulators such as KIF20A and GPSM2. Finally, potent synergy between XI-006 and olaparib (PARP inhibitor) were observed due to the down-regulation of Mre11. Our findings suggest that XI-006 represents a novel therapeutic intervention for the treatment of Ewing sarcoma.

The Well-Being of Australian Service Mothers.

In recent years servicewomen with dependent children have for the first time in history been deployed into conflict zones in support of Australian Defence Force operations. This represents a significant social change, and the implications of deployment on the health of these service mothers are not fully understood. Data from women who participated in the Middle East Area of Operations Census study were analyzed to compare the psychological and physical symptoms reported by service mothers with service women who had no dependent children at the time of deploying to Afghanistan and/or Iraq. Of the 921 women who were included in this analysis, 235 had dependent children and 686 had no dependent children (comparison group). Service mothers were significantly older and were more likely to have served in the Air Force than women in the comparison group. Findings demonstrate that serving mothers were not at any significantly higher risk of psychological distress, post-traumatic stress symptoms, alcohol misuse, or reporting of somatic symptoms, than women who had no dependent children. A number of possible explanations for these findings are discussed, including the healthy soldier/mother effect, support from partners and extended family members, and collegial networks.

Seroprevalence of Strongyloides stercoralis in a South Australian Vietnam veteran cohort.

OBJECTIVES: Strongyloides stercoralis is a parasitic roundworm causing chronic infection that is endemic in Southeast Asia. Vietnam veterans are considered to be at high risk of Strongyloides infection. The prevalence of persistent infection in this group is unknown. This study aimed to establish the seropositivity rate of Strongyloides antibodies in South Australian Vietnam veterans and to identify the most reported symptoms within the seropositive group. METHOD: This cross-sectional study recruited 309 veterans who had served in Vietnamese territory between 1962 and 1975 and were currently resident in South Australia. Participants completed a self-administered questionnaire examining demographics, deployment, somatic symptoms and depression. Venous blood was collected for Strongyloides serology and eosinophil count. Participants who demonstrated positive Strongyloides serology underwent faecal microscopy for parasites. RESULTS: A total of 309 participants were recruited and 256 completed the questionnaire. Strongyloides seropositivity was demonstrated in 29 of 249 participants (11.6%). No participant had Strongyloides larvae detected by faecal microscopy. On multivariate analysis, only dermatological symptoms were associated with positive serology (OR 4.84, 95%CI 1.31-17.92, p-value 0.01). CONCLUSIONS: This study found a high seroprevalence (11.6%) of Strongyloides antibodies within the Vietnam veteran community in South Australia. Seropositivity was associated with increased likelihood of dermatological symptoms. IMPLICATIONS: Post-deployment screening and eradication therapy for Strongyloides should be offered to ADF staff after service in Strongyloides-endemic areas. This should include those veterans who left the service many years ago.

Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma.

PURPOSE: This international, multicenter, single-arm trial assessed efficacy and safety of intralesional rose bengal (PV-10) in 80 patients with refractory cutaneous or subcutaneous metastatic melanoma. METHODS: Sixty-two stage III and 18 stage IV melanoma patients with disease refractory to a median of six prior interventions received intralesional PV-10 into up to 20 cutaneous and subcutaneous lesions up to four times over a 16-week period and were followed for 52 weeks. Objectives were to determine best overall response rate in injected target lesions and uninjected bystander lesions, assess durability of response, and characterize adverse events. RESULTS: For target lesions, the best overall response rate was 51 %, and the complete response rate was 26 %. Median time to response was 1.9 months, and median duration of response was 4.0 months, with 8 % of patients having no evidence of disease after 52 weeks. Response was dependent on untreated disease burden, with complete response achieved in 50 % of patients receiving PV-10 to all of their disease. Response of target lesions correlated with bystander lesion regression and the occurrence of locoregional blistering. Adverse events were predominantly mild to moderate and locoregional to the treatment site, with no treatment-associated grade 4 or 5 adverse events. CONCLUSIONS: Intralesional PV-10 yielded durable local control with high rates of complete response. Toxicity was confined predominantly to the injection site. Cutaneous bystander tumor regression is consistent with an immunologic response secondary to ablation. This intralesional approach for local disease control could be complementary to current and investigational treatments for melanoma.

The experience of melanoma follow-up care: an online survey of patients in australia.

Investigating patients' reports on the quality and consistency of melanoma follow-up care in Australia would assist in evaluating if this care is effective and meeting patients' needs. The objective of this study was to obtain and explore the patients' account of the technical and interpersonal aspects of melanoma follow-up care received. An online survey was conducted to acquire details of patients' experience. Participants were patients treated in Australia for primary melanoma. Qualitative and quantitative data about patient perceptions of the nature and quality of their follow-up care were collected, including provision of melanoma specific information, psychosocial support, and imaging tests received. Inconsistencies were reported in the provision and quality of care received. Patient satisfaction was generally low and provision of reassurance from health professionals was construed as an essential element of quality of care. "Gaps" in follow-up care for melanoma patients were identified, particularly provision of adequate psychosocial support and patient education. Focus on strategies for greater consistency in the provision of support, information, and investigations received, may generate a cost dividend which could be reinvested in preventive and supportive care and benefit patient well-being.