A Randomised Phase II Trial to Evaluate the Feasibility of Radiotherapy Dose Escalation, Facilitated by Intensity-Modulated Arc Radiotherapy Techniques, in High-Risk Neuroblastoma.

BACKGROUND AND PURPOSE: For high-risk neuroblastoma, planning target volume coverage is often compromised to respect adjacent kidney tolerance. This trial investigated whether intensity-modulated arc radiotherapy techniques (IMAT) could facilitate dose escalation better than conventional techniques. MATERIALS AND METHODS: Children with high-risk abdominal neuroblastoma referred for radiotherapy to the primary tumour site and involved regional lymph nodes were randomised to receive either standard dose (21 Gy in 14 fractions) or escalated dose (36 Gy in 24 fractions) radiotherapy. Dual planning with both a conventional anterior-posterior parallel opposed pair radiotherapy technique and an IMAT technique was performed. The quality of target volume and organ-at-risk delineation, and dosimetric plans, were externally reviewed. Dosimetric parameters were used to judge the superior technique for treatment. This feasibility trial was not powered to detect improvement in outcome with dose escalation. RESULTS: Between 2017 and 2020, 50 patients were randomised and dual-planned. The IMAT technique was judged more favourable in 48 patients. In all patients randomised to receive 36 Gy, IMAT would have permitted delivery of the full dose (median D50% 36.0 Gy, inter-quartile range 36.0-36.1 Gy) to the target volume, whereas dose compromise would have been required with conventional planning (median D50% 35.6 Gy, inter-quartile range 28.7-35.9 Gy). CONCLUSION: IMAT facilitates safe dose escalation to 36 Gy in patients receiving radiotherapy for neuroblastoma. The value of dose escalation is now being evaluated in a current prospective phase III randomised trial.

Clinical Implementation of Robust Multi-isocentric Volumetric Modulated Arc Radiotherapy for Craniospinal Irradiation.

AIMS: To determine if multi-isocentric volumetric modulated arc radiotherapy for craniospinal irradiation (CSI-VMAT) can be implemented safely and accurately using robust optimisation in a commercially available treatment planning system. Our initial clinical experience is reported for the first 20 patients treated with the technique. MATERIALS AND METHODS: Patients received between 23.4 and 39.6 Gy (mode 23.4 Gy) in 13-22 fractions with CSI-VMAT. The heart mean dose was 4.2-10.3 Gy (median 5.3 Gy) for patients prescribed up to 24 Gy and 6.5-16.3 Gy (median 10.1 Gy) for patients receiving 35 Gy or more. The lung mean dose was 5.5-7.6 Gy (median 6.8 Gy) for patients prescribed up to 24 Gy and 6.9-11.1 Gy (median 10.0 Gy) for patients receiving 35 Gy or more. The robustness of the planning target volume D0.1cm3 and D99% to systematic errors in the isocentre superoinferior position of up to 5 mm was evaluated. These remained acceptable but were correlated to the length of the available beam overlap through the neck. RESULTS: As of January 2021, one patient was deceased after 508 days and one patient was lost to follow-up after completing treatment. The median follow-up was 399 days (range 175-756 days) and progression-free survival was 131 days (34-490 days). Acute toxicities at Common Terminology Criteria for Adverse Events v5.0 grade 3+ included lowered white blood cell count (16/20), decreased platelet count (8/20), nausea (5/20), vomiting (2/20), pharyngeal mucositis (1/20) and oral mucositis (1/20). Three patients developed grade 4 neutropenia or decreased white blood cell count. CONCLUSIONS: CSI-VMAT can be implemented safely and accurately using robust optimisation functions in a commercially available treatment planning system.

Treatment of acute aneurysmal subarachnoid haemorrhage with primary flow diversion: 5-year single-centre experience.

AIM: To evaluate the safety and efficacy of treatment of patients presenting with acute aneurysmal subarachnoid haemorrhage (SAH) with primary flow-diverting stents (FDS; with or without adjuncts), with comparison to the published literature. MATERIALS AND METHODS: A retrospective single-centre review was undertaken of prospectively obtained data on patients treated for SAH over a 60-month period. Of 354 patients treated for SAH during that time period, 24 patients with a total of 25 aneurysms were identified. Baseline patient demographics were recorded and clinical and imaging outcomes assessed. RESULTS: Eighty-eight per cent (22/25) of the aneurysms were completely occluded (Raymond-Roy 1) at mean 12-month follow-up. The minor complication rate was 12.5% (3/24) without permanent morbidity. Mortality rate was 4% (1/25) after one patient died following aneurysmal rebleed on day 7 post-procedure. Forty-two per cent (10/24) of patients had a high-pressure shunt placed prior to endovascular treatment, no haemorrhagic complications of neurosurgical intervention were observed. CONCLUSION: The necessity of dual antiplatelet therapy (DAPT) therapy when deploying FDS will rightly continue to limit their use in the acutely ruptured setting to a case-by-case basis whereby other treatment options are deemed unsafe. Methods employed to minimise subsequent haemorrhagic risks from DAPT in these patients may be worthy of further investigation.

Publisher Correction: Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer.

The original version of this Article contained an error in Fig. 4. In the left histogram of the right panel of Fig. 4d, several data points were inadvertently deleted from the histogram during the production process. This error has been corrected in both the PDF and HTML versions of the Article. The original, incorrect version of Fig. 4 is presented in the accompanying Publisher Correction.

Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer.

Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases are poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) to track the spatio-temporal fate of thousands of barcoded clones in primary tumors, and their metastases. Tumor resection had a major impact on reducing clonal diversity in secondary sites, indicating that most disseminated tumor cells lacked the capacity to 'seed', hence originated from 'shedders' that did not persist. The few clones that continued to grow after resection i.e. 'seeders', did not correlate in frequency with their parental clones in primary tumors. Cisplatin treatment of one BRCA1-mutated PDX model to non-palpable levels had a surprisingly minor impact on clonal diversity in the relapsed tumor yet purged 50% of distal clones. Therefore, clonal features of shedding, seeding and drug resistance are important factors to consider for the design of therapeutic strategies.

Long-term outcomes of en-bloc renal transplantation from paediatric donors into adult recipients.

INTRODUCTION: Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. METHODS: Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. RESULTS: Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36-264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients (p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36-172). Mean serum creatinine was 72.6 ± 21.6 µmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. CONCLUSION: En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.

Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release.

BACKGROUND: Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli. METHODS: Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. RESULTS: Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.

Patient reported functional outcomes following robotic-assisted (RARP), laparoscopic (LRP), and open radical prostatectomies (ORP).

BACKGROUND: Radical prostatectomy for prostate cancer is associated with significant complications, such as urinary incontinence and erectile dysfunction. Debate remains regarding the influence of surgical technique on these important functional outcomes. AIM: The aim of this study was to compare the early functional outcomes following robotic-assisted (RARP), laparoscopic (LRP), and open radical prostatectomy (ORP) in a rapid access cohort. METHODS: A retrospective review of a prospectively maintained database was performed between 2011 and 2014. Functional status was objectively assessed using the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and a self-reported continence score. RESULTS: Two hundred and ninety-two patients underwent RP (85 RARP, 100 LRP, 107 ORP). The mean age was 61.3 years with a mean initial PSA was 6.2 ng/ml. There was no difference noted in urinary function between ORP, LRP, and RARP at 3 months (p = 0.894), 6 months (p = 0.244), 9 months (p = 0.068) or 12 months (p = 0.154). All men noted a deterioration in erectile function; however, there was no difference at 3 months (p = 0.922), 6 months (p = 0.723), 9 months (p = 0.101) or 12 months (p = 0.395), CONCLUSION: Equivalent good early functional outcomes are being achieved in patients undergoing RP irrespective of surgical approach. Longer follow-up in a prospective randomized fashion is required to fully assess the most appropriate surgical technique.

Efficacy of vacuum erectile devices (VEDs) after radical prostatectomy: the initial Irish experience of a dedicated VED clinic.

Controversy exists regarding optimal penile rehabilitation program following radical prostatectomy (RP). Vacuum erectile devices (VEDs) have become an important component of penile rehabilitation protocols. The aim of this study was to assess the efficacy and patient satisfaction of a dedicated VED clinic. A voluntary telephone questionnaire was performed of all patients who attended a VED clinic to date in two university teaching hospitals. Patient demographics, histopathological characteristics and functional status (International Index of Erectile Function (IIEF) scores) were obtained from a retrospective review of a prospectively maintained database. Sixty-five men attended the dedicated VED clinic in the two university teaching hospitals. Forty-men (76.3%) men purchased a VED following the dedicated clinic. There was significant differences noted between the mean preoperative and the 3-month postoperative IIEF scores (22.08±3.16 vs 11.3±3.08, P=0.0001) and between the 3-month postoperative IIEF score and the post-VED use IIEF score (11.3±3.08 vs 16.74±2.62, P=0.0001). Despite VED use, there was a significant reduction in erectile function from presurgery status (22.08±3.16 vs 16.74±2.62, P=0.0001). All patients reported that the dedicated VED was helpful and would recommend it to other patients. Our study demonstrates that, despite a reduction in erectile function after RP, successful erections are attainable with a VED. There is potential and need for the development of a standard penile rehabilitation program and treatment of ED after RP internationally.

Demographics of Australian horses: results from an internet-based survey.

OBJECTIVE: To obtain information on the types of Australian horses, how they are kept and their activities. METHODS: An invitation to participate in an opt-in, internet-based survey was sent to 7000 people who had registered an email address to receive information from the Australian Horse Industry Council Inc. RESULTS: There were 3377 (48%) useable responses from owners of 26,548 horses. Most horses were kept on small properties (usually 2-8 ha) in paddocks in rural areas of Queensland, New South Wales and Victoria. Most horses were female or geldings and the most common of 54 different activities was breeding. Owners reported 19,291 horses were used in different activities and 6037 (23%) horses were not kept for any stated purpose or activity. Owners used an average of 1.95 horses in 2.9 different types of activities. The most common of the 43 breeds were Thoroughbred, Australian Stock Horse and Australian Quarter Horse. Only 1% of the total numbers of Thoroughbreds and Standardbreds in this survey were used in horse racing, indicating there is a demand for these breeds in non-racing activities. Microchip was the most favoured method of horse identification and 36% favoured compulsory registration of horses. Most respondents reported owning some other animal species. CONCLUSIONS: There is a wide variation in horse breeds used in different activities by Australian horse owners. There are regional differences in various management systems. There needs to be considerable improvement in the collection and recording of information to improve the validity and reliability of horse industry data.

Collation of data on applicants, offers, acceptances, students and graduates in veterinary science in Australia 2001-2013.

OBJECTIVE: To collate data on the numbers of applications, offers, acceptances, students and graduates at Australian veterinary schools between 2001 and 2013. METHOD: Data were obtained from the Australian Department of Education, the Australian Bureau of Statistics, Graduate Careers Australia and the Australian Veterinary Association Ltd. RESULTS: The number of eligible applicants for veterinary science courses increased from 1540 in 2001 to 2243 in 2013 (46% increase). Offers for places ranged from 400 in 2001 to 643 in 2013 (61% increase) and acceptances ranged from 254 in 2001 to 457 in 2013 (80% increase).The total number of students enrolled ranged from 1641 in 2001 to 3036 in 2013 (85% increase). Female students increased from 1195 in 2001 to 2340 in 2013 (96% increase) and male students increased from 446 to 696 (56%) over this time period. Domestic students numbered 1411 in 2001 and 2391 in 2013 (69% increase). International students increased from 230 in 2001 to 643 in 2013 (180% increase). Students entering veterinary courses numbered 389 in 2001 and increased to 688 in 2013 (77% increase). Graduates increased from 312 in 2001 to 561 in 2013 (80% increase). Percent of recent veterinary graduates seeking full-time employment was 7.6% in 2001 and increased to 21.2% in 2013. Median starting salaries for veterinary graduates in Australia were A$34,000 in 2001 and A$46,000 in 2013 (35% increase). CONCLUSIONS: These data provide additional information about the ongoing increase in the numbers of domestic and international students studying veterinary science at Australian universities. Between 2001 and 2013 the numbers of Australian veterinary students and graduates increased at a greater rate than the Australian population.

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women.

AIMS: The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. METHODS: Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed. RESULTS: In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum. INTERPRETATION: The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.

Single centre experience of hypothermic machine perfusion of kidneys from extended criteria deceased heart-beating donors: a comparative study.

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.

Distinctive pro-inflammatory gene signatures induced in articular chondrocytes by oncostatin M and IL-6 are regulated by Suppressor of Cytokine Signaling-3.

OBJECTIVE: To describe gene expression in murine chondrocytes stimulated with IL-6 family cytokines and the impact of deleting Suppressor of Cytokine Signaling-3 (SOCS-3) in this cell type. METHOD: Primary chondrocytes were isolated from wild type and SOCS-3-deficient (Socs3(Δ/Δcol2)) mice and stimulated with oncostatin M (OSM), IL-6 plus the soluble IL-6 receptor (IL-6/sIL-6R), IL-11 or leukemia inhibitory factor (LIF) for 4 h. Total RNA was extracted and gene expression was evaluated by microarray analysis. Validation of the microarray results was performed using Taqman probes on RNA derived from chondrocytes stimulated for 1, 2, 4 or 8 h. Gene ontology was characterized using DAVID (database for annotation, visualization and integrated discovery). RESULTS: Multiple genes, including Bcl3, Junb, Tgm1, Angptl4 and Lrg1, were upregulated in chondrocytes stimulated with each gp130 cytokine. The gene transcription profile in response to OSM stimulation was pro-inflammatory and was highly correlated to IL-6/sIL-6R, rather than IL-11 or LIF. In the absence of SOCS-3, OSM and IL-6/sIL-6R stimulation induced an interferon (IFN)-like gene signature, including expression of IL-31ra and S100a9. CONCLUSION: While each gp130 cytokine induced a transcriptional response in chondrocytes, OSM- and IL-6/sIL-6R were the most potent members of this cytokine family. SOCS-3 plays an important regulatory role in this cell type, as it does in hematopoietic cells. Our results provide new insights into a hierarchy of gp130-induced transcriptional responses in chondrocytes that is normally restrained by SOCS-3 and suggest therapeutic inhibition of OSM may have benefit over and above antagonism of IL-6 during inflammatory arthritis.

Spatial and temporal evaluation of veterinarians and veterinary employers relative to human and domesticated animal populations in Australia 2002-2012.

OBJECTIVES: To examine the distribution of veterinarians, humans, domestic animals and non-private practice employers in Australia and assess whether a relationship exists between them. To identify trends in the number of veterinarians, humans and domestic animals between 2002 and 2012 that may influence future demands for veterinary services. METHODS: Australian data on registered veterinarians, veterinary practices, the human population and various domestic animal species were obtained for the years 2002, 2007 and 2012. The data were mapped to assess distribution and temporal trends in number and distribution were assessed. RESULTS: Nationally, registered veterinarians were distributed similarly to the general population, with a slight bias to regional areas. The number of veterinarians nationally increased both in absolute terms and relative to the human population between 2002 and 2012. Companion animals were distributed similarly to the human population and livestock occurred in highest density in the more productive agricultural areas. The areas with highest density of domestic animals were within 100 km of an existing veterinary practice. There was moderate correlation between the number of registered veterinarians and the number of people or companion animals, but poor correlation for livestock. The number of domestic animal species decreased between 2002 and 2012, with the exceptions of cattle and poultry. CONCLUSIONS: There is not a simple relationship between the number of veterinarians, people or domestic animals. Better data are needed to describe the drivers for demand for veterinary services and enable future workforce planning.

MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway.

Cellular senescence is an important mechanism that restricts tumour growth. The Ink4a-Arf locus (also known as Cdkn2a), which encodes p16(INK4A) and p19(ARF), has a central role in inducing and maintaining senescence. Given the importance of cellular senescence in restraining tumour growth, great emphasis is being placed on the identification of novel factors that can modulate senescence. The MYST-family histone acetyltransferase MOZ (MYST3, KAT6A), first identified in recurrent translocations in acute myeloid leukaemia, has been implicated in both the promotion and inhibition of senescence. In this study, we investigate the role of MOZ in cellular senescence and show that MOZ is a potent inhibitor of senescence via the INK4A-ARF pathway. Primary mouse embryonic fibroblasts (MEFs) isolated from Moz-deficient embryos exhibit premature senescence, which was rescued on the Ink4a-Arf(-/-) background. Importantly, senescence resulting from the absence of MOZ was not accompanied by DNA damage, suggesting that MOZ acts independently of the DNA damage response. Consistent with the importance of senescence in cancer, expression profiling revealed that genes overexpressed in aggressive and highly proliferative cancers are expressed at low levels in Moz-deficient MEFs. We show that MOZ is required to maintain normal levels of histone 3 lysine 9 (H3K9) and H3K27 acetylation at the transcriptional start sites of at least four genes, Cdc6, Ezh2, E2f2 and Melk, and normal mRNA levels of these genes. CDC6, EZH2 and E2F2 are known inhibitors of the INK4A-ARF pathway. Using chromatin immunoprecipitation, we show that MOZ occupies the Cdc6, Ezh2 and Melk loci, thereby providing a direct link between MOZ, H3K9 and H3K27 acetylation, and normal transcriptional levels at these loci. This work establishes that MOZ is an upstream inhibitor of the INK4A-ARF pathway, and suggests that inhibiting MOZ may be one way to induce senescence in proliferative tumour cells.

Activated Notch counteracts Ikaros tumor suppression in mouse and human T-cell acute lymphoblastic leukemia.

Activating NOTCH1 mutations occur in ~60% of human T-cell acute lymphoblastic leukemias (T-ALLs), and mutations disrupting the transcription factor IKZF1 (IKAROS) occur in ~5% of cases. To investigate the regulatory interplay between these driver genes, we have used a novel transgenic RNA interference mouse model to produce primary T-ALLs driven by reversible Ikaros knockdown. Restoring endogenous Ikaros expression in established T-ALL in vivo acutely represses Notch1 and its oncogenic target genes including Myc, and in multiple primary leukemias causes disease regression. In contrast, leukemias expressing high levels of endogenous or engineered forms of activated intracellular Notch1 (ICN1) resembling those found in human T-ALL rapidly relapse following Ikaros restoration, indicating that ICN1 functionally antagonizes Ikaros in established disease. Furthermore, we find that IKAROS mRNA expression is significantly reduced in a cohort of primary human T-ALL patient samples with activating NOTCH1/FBXW7 mutations, but is upregulated upon acute inhibition of aberrant NOTCH signaling across a panel of human T-ALL cell lines. These results demonstrate for the first time that aberrant NOTCH activity compromises IKAROS function in mouse and human T-ALL, and provide a potential explanation for the relative infrequency of IKAROS gene mutations in human T-ALL.

Demographics of Australian horse owners: results from an internet-based survey.

OBJECTIVES: To obtain information on the demographics of Australian horse owners. METHODS: An invitation to participate in an opt-in, internet-based survey was sent to 7000 persons who had registered an email address to receive information from the Australian Horse Industry Council Inc. These horse owners represented approximately 1.75% of the total horse owners in Australia. The survey was available for completion between 1 and 31 July 2009. RESULTS: There were 3377 (48%) useable responses. The respondents were a self-selected group of approximately 0.85% of the estimated total horse owners in Australia. The overall geographic distribution of respondents was the same as the general population at a state and territory level. In general, respondents were female and aged between 31 and 60 years; most lived in rural areas of Queensland, New South Wales or Victoria; had at least a secondary education, but no formal horse industry qualification; had a higher weekly income if based in a capital city; earned less than 10% of weekly income from horse-related activities; were a member of more than one horse industry organisation; reported an affiliation with one of more than 300 different horse industry organisations; spent 10-30% of their daily time with horses; and preferred to receive information by email. CONCLUSIONS: The responses from this survey of horse owners provided demographic information that was previously unavailable. Horse owners tended to be older than the general population, had a higher level of education attainment, were in higher weekly income brackets and lived mostly in non-metropolitan areas of Australia. Because of the self-selection and small sample size, the results need to be interpreted with caution. Nevertheless, the present results are compatible with other smaller random and non-random surveys of horse owners internationally.

A single centre experience of active surveillance as management strategy for low-risk prostate cancer in Ireland.

INTRODUCTION: Active surveillance (AS) is a management strategy for addressing the widely acknowledged problem of over diagnosis and over treatment of clinically indolent prostate cancer. METHODS: A total of 80 patients were enrolled on the AS program in our institution between January 2008 and June 2012. All data were collected prospectively in a secure database. RESULTS: The mean age of patients enrolled was 62.7 years (range 50-72). Median PSA at enrolment was 5.6 ng/mL (range 1.2-13.4). The mean follow-up was 32 months (range 2-54). In total, 85 % of patients had a repeat biopsy after 1-year with 30 % having another biopsy after 3 years. Overall, 45 % of patients remain on AS. In the remainder; 42.5 % of patients have been removed from AS for definitive treatment, while 8.75 % of patients are now on watchful waiting, 2.5 % of patients self discharged from the program and one patient died of cardiovascular disease. The prostate cancer specific survival rate is 100 %. Reasons for removal from AS and referral for treatment were; 67.6 % of patients had upgrade of disease on repeat biopsy, 17.6 % of patients had PSA progression, 11.8 % patients had progression of disease on MRI, and one patient developed a palpable nodule. Regarding definitive treatment; 52.9 % of patients have been for referred for external beam radiotherapy, 14.7 % have been referred for brachytherapy, 29.4 % have been referred for surgery and one patient has refused definitive treatment. CONCLUSION: Our findings to date support active surveillance as a valid strategy for early, localised prostate cancer.

Incidence and long-term outcomes of squamous cell bladder cancer after deceased donor renal transplantation.

OBJECTIVE: To review the incidence and long-term outcomes of squamous cell carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS: Between January 1976 and March 2013, five patients from one center (0.0013%) developed SCC of the bladder after undergoing a deceased donor kidney transplant. Their relevant risk factors included long-term self-intermittent catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome variables were overall patient survival and latency period between transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up was 94 ± 89 (range: 4-239) months. The latency period between transplantation and bladder SCC was 87 ± 87 (range: 2-228) months, and all five patients were immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four patients had suspected metastases upon presentation, and one patient presented with organ-confined disease. This patient underwent a radical cystectomy and remains disease free eight months post-operatively. Despite radical treatment, the remaining four patients died from metastatic disease 7 ± 4.4 (range: 2-11) months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor prognosis particularly in renal transplant patients. Early detection with flexible cystourethroscopy in patients with risk factors for SCC may improve long-term outcomes in this patient cohort.