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A 41 years-old male patient presented acutely with severe right testicular pain, and fever for 48 hours. Patient had a backround of previous left orchidectomy for epididymo-orchitis and sexually-transmitted disease. A clinical diagnosis of right epididymo-orchitis was made and patient was treated with intravenous broad-spectrum antibiotic. However subsequent ultrasound revealed imminent testicular ischaemia. Given the challenging nature of the case, i.e. single testicle with testicular ischaemia, surgical exploration, fasciotomy and tunica vaginalis grafting was performed to the patient. The patient recovered fully post-operatively with ultrasound proving restoration of end-diastolic flow to the testicle.

Background Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent phase III cohort to evaluate the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker in localized PC. Patients and methods In our multicentre, prospective phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous phase II study. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and PC-specific survival (PCSS). Results In the phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4; 95% CI, 1.1–1.9; P = 0.03), MFS (HR, 2.8; 95% CI, 1.2–6.6;P = 0.02) and PCSS (HR, 3.8; 95% CI, 1.5–9.5;P = 0.005). These results were validated in our prospective phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.9; 95% CI, 1.1–3.3;P = 0.02), with shorter MFS (HR, 2.0; 95% CI, 1.1–3.4;P = 0.02). AZGP1 improved the discriminatory value when incorporated into existing prognostic risk models. Conclusion Our study provides prospective phase III validation that absent/low AZGP1 expression provides independent prognostic value in PC. This study provides robust evidence for the incorporation of this biomarker into clinical practice.

Background Total cystectomy and subsequent reconstruction of the urinary tract may be required for primary malignancy of the bladder, or in the context of multi-visceral resection for more advanced pelvic tumors. Complications following urinary diversion are a major source of morbidity, particularly in pelvic exenteration (PE) patients. Methods All patients who underwent radical cystectomy alone or during PE at a single tertiary referral centre between 2008 and 2014 were reviewed. Postoperative urological complications were collected and compared between groups. Results Two hundred and thirty-one patients underwent en bloc cystectomy (98 cystectomy alone, 133 as part of a PE). Postoperative urological complications occurred in 33% of the cystectomy alone group and 59% of the PE group (P

Aims Ductal adenocarcinoma is a rare variant of prostate cancer, and as such clinical outcomes and best management are not well defined. This series demonstrates the atypical presentation and unusual clinical behaviour of ductal adenocarcinoma and proposes management guidelines to assist clinicians. Materials and methods A retrospective review of pure (nine patients) and mixed (18 patients) ductal adenocarcinoma of the prostate referred to the Departments of Radiation Oncology of the Sydney Cancer Centre, Royal Prince Alfred Hospital and Northern Sydney Cancer Centre, Royal North Shore Hospital, between 2000 and 2015. Results Twenty-seven patients were treated with definitive radiotherapy, nine patients (33%) with pure ductal and 18 (67%) with mixed ductal-acinar adenocarcinoma. The median follow-up was 38 months. Four patients (15%) failed locally, all of whom received less than 80 Gy, or no brachytherapy boost. Five patients (19%) failed distantly, four with biopsy-proven lung metastases. All distant failures occurred with a prostate-specific antigen (PSA) Conclusion This series shows the atypical clinical presentation of this entity, as well as its propensity to metastasise to unusual sites. Relapse may occur at low absolute PSA values and is often asymptomatic. Ductal cancer should not simply be regarded as a high Gleason grade cancer. We propose management guidelines, including regular computed tomography examinations (rather than relying solely on PSA levels) as part of the follow-up for patients with any component of ductal adenocarcinoma.

Purpose To investigate diffusion anisotropy in whole human prostate specimens Methods Seven whole radical prostatectomy specimens were obtained with informed patient consent and institutional ethics approval. Diffusion tensor imaging was performed at 9.4 Tesla. Diffusion tensors were calculated from the native acquired data and after progressive downsampling Results Fractional anisotropy (FA) decreased as voxel volume increased, and differed widely between prostates. Fixation decreased mean FA by ∼0.05–0.08 at all voxel volumes but did not alter principle eigenvector orientation. In unfixed tissue high FA (> 0.6) was found only in voxels of volume 0.25. FA decreased at longer diffusion times (Δ = 60 or 80 ms compared with 20 ms), but only by ∼0.02 at typical clinical voxel volume. Peripheral zone FA was significantly lower than transition zone FA in five of the seven prostates Conclusion FA varies widely between prostates. The very small proportion of clinical size voxels with high FA suggests that in clinical DWI studies ADC based on three-direction measurements will be minimally affected by anisotropy. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

// Mu Yao 1, 2 , Chanlu Xie 1, 2, 3 , Mei-Yee Kiang 1, 2 , Ying Teng 1, 2 , David Harman 4 , Jessamy Tiffen 5, 6 , Qian Wang 5, 6 , Paul Sved 7 , Shisan Bao 8 , Paul Witting 8 , Jeff Holst 5, 6 , Qihan Dong 1, 2, 3 1 Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia 2 Central Clinical School and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia 3 School of Biomedical and Health Sciences, University of Western Sydney, Parramatta, NSW 2751, Australia 4 Molecular Medicine Research Group, University of Western Sydney, Parramatta, NSW 2751, Australia 5 Origins of Cancer Laboratory, Centenary Institute, Camperdown, NSW 2050, Australia 6 Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia 7 Department of Urology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia 8 Department of Pathology, The University of Sydney, Sydney, NSW 2006, Australia Correspondence to: Qihan Dong, e-mail: q.dong@uws.edu.au Mu Yao, e-mail: mu.yao@sydney.edu.au Keywords: prostate cancer, phospholipase A2α, cell cycle re-entry, p27, Skp2 Received: May 15, 2015 Accepted: September 14, 2015 Published: September 24, 2015 ABSTRACT Cell cycle re-entry of quiescent cancer cells has been proposed to be involved in cancer progression and recurrence. Cytosolic phospholipase A 2 α (cPLA 2 α) is an enzyme that hydrolyzes membrane glycerophospholipids to release arachidonic acid and lysophospholipids that are implicated in cancer cell proliferation. The aim of this study was to determine the role of cPLA 2 α in cell cycle re-entry of quiescent prostate cancer cells. When PC-3 and LNCaP cells were rendered to a quiescent state, the active form of cPLA 2 α with a phosphorylation at Ser 505 was lower compared to their proliferating state. Conversely, the phospho-cPLA 2 α levels were resurgent during the induction of cell cycle re-entry. Pharmacological inhibition of cPLA 2 α with Efipladib upon induction of cell cycle re-entry inhibited the re-entry process, as manifested by refrained DNA synthesis, persistent high proportion of cells in G 0 /G 1 and low percentage of cells in S and G 2 /M phases, together with a stagnant recovery of Ki-67 expression. Simultaneously, Efipladib prohibited the emergence of Skp2 while maintained p27 at a high level in the nuclear compartment during cell cycle re-entry. Inhibition of cPLA 2 α also prevented an accumulation of cyclin D1/CDK4, cyclin E/CDK2, phospho-pRb, pre-replicative complex proteins CDC6, MCM7, ORC6 and DNA synthesis-related protein PCNA during induction of cell cycle re-entry. Moreover, a pre-treatment of the prostate cancer cells with Efipladib during induction of cell cycle re-entry subsequently compromised their tumorigenic capacity in vivo . Hence, cPLA 2 α plays an important role in cell cycle re-entry by quiescent prostate cancer cells.

Radiation therapy is used to treat cancer by radiation-induced DNA damage. Despite the best efforts to eliminate cancer, some cancer cells survive irradiation, resulting in cancer progression or recurrence. Alteration in DNA damage repair pathways is common in cancers, resulting in modulation of their response to radiation. This article focuses on the recent findings about molecules and pathways that potentially can be targeted to sensitize prostate cancer cells to ionizing radiation, thereby achieving an improved therapeutic outcome.

Item does not contain fulltext CONTEXT: Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach. OBJECTIVE: To critically review the recent data on the management of NMIBC to arrive at a general consensus. EVIDENCE ACQUISITION: A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched. EVIDENCE SYNTHESIS: The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies. CONCLUSIONS: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy.

To investigate the hypothesis that the clinically observed decrease in apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance imaging with increasing prostate cancer Gleason grade can be attributed to an increasing volume of low-diffusivity epithelial cells and corresponding decreasing volumes of higher-diffusivity stroma and lumen space rather than to increased cell density.Tissue samples were acquired after institutional ethics review committee approval and informed consent from patients were obtained. Nuclear count, nuclear area, and gland component volumes (epithelium, stroma, lumen space) were measured in tissue from 14 patients. Gland component volumes and cellularity metrics were correlated with Gleason pattern (Spearman rank correlation coefficient) and measured ADC (Pearson correlation coefficient) in six prostates ex vivo. Differences between metrics for cancerous tissue and those for normal tissue were assessed by using a two-tailed two-sample t test. Linear mixed models with a post hoc Fisher least significant difference test were used to assess differences between gland component volumes and cellularity metrics for multiple groups. To adjust for a clustering effect due to repeated measures, the organ mean value of the measured metric for each tissue type was used in the analysis.There were significant differences between Gleason patterns for gland component volumes (P.05) but not nuclear count (P = .100) or area (P = .141). There was a stronger correlation of Gleason pattern with gland component volumes (n = 553) of epithelium (Spearman ρ = 0.898, P.001), stroma (ρ = -0.651, P.001), and lumen space (ρ = -0.912, P = .007) than with the cellularity metrics (n = 288) nuclear area (ρ = 0.422, P = .133) or nuclear count (ρ = 0.082, P = .780). There was a stronger correlation between measured ADC and lumen volume (r = 0.688, P.001) and epithelium volume (r = -0.647, P.001) than between ADC and nuclear count (r = -0.598, P.001) or nuclear area (r = -0.569, P.001) (n = 57).Differences in the gland compartment volumes of prostate tissue having distinct diffusivities, rather than changes in the conventionally cited "cellularity" metrics, are likely to be the major contributor to clinically observed variations of ADC in prostate tissue.

Mortality from prostate cancer is a result of progression of cancer cells to become androgen-refractory and metastatic. Eicosanoid products of the cyclooxygenase (COX) and lipoxygenase (LOX) pathways are important mediators of the proliferation of prostate cancer cells in culture and regulate tumour vascularisation and metastasis in animal models. Pharmacological agents that block either COX or LOX products effectively reduce the size of prostate cancer xenografts. Recently, phospholipase A(2) (PLA(2)) enzymes, which regulate the provision of arachidonic acid to both COX- and LOX-derived eicosanoids, are found to also regulate the growth of prostate cancer cells and tumours, with one enzyme, secreted PLA(2)-IIA, being increased in prostate cancer tissues. Annexin A1 and A2, known inhibitors of cytosolic phospholipase A(2)-alpha activity, are absent in prostate cancer tissues. We propose that PLA(2) enzyme function is dysregulated by aberrant up regulation of secreted enzymes and downregulation of endogenous inhibitors of cytosolic phospholipase A(2) activity in prostate cancer and that this dysregulation contributes to the pathogenesis of prostate cancer. Thus, in addition to COX and LOX enzymes, PLA(2) enzymes represent important targets for the treatment of prostate cancer.

Localized surgical therapy and surveillance examines the evidence and practice of two of the most important aspects of management of localized bladder cancer. The first part, surgical therapy, comprises preoperative assessment (including preoperative imaging studies, laboratory investigations, and antibiotic prophylaxis) followed by transurethral resection of bladder tumor. This section explores the principles of TURBT, including resection depth, staged resections, and bladder drainage. Specific circumstances such as tumors at the ureteral orifices, lateral/anterior walls, within diverticulae and reresection are specifically addressed.

Pain is a significant problem following spinal cord injury (SCI) and has a major influence on quality of life and the ability to engage in rehabilitation. Surgery is often indicated in the management of spinal cord injury to stabilise the spine and prevent further neurological deficit. However, the relationship between surgical intervention and the presence of pain following SCI is unclear. We performed a prospective, longitudinal study of 100 individuals with traumatic SCI to determine the prevalence of different types of SCI pain at 2, 4, 8, 13, 26 and 52 weeks following SCI and to determine whether there was a relationship between surgical intervention and the presence or absence of specific types of SCI pain. We found that surgical intervention was associated with a significantly higher prevalence of musculoskeletal pain at 2 weeks but not at 4, 8, 13, 26 and 52 weeks following injury, when compared with those who did not have surgery. There were no significant differences in the prevalence of visceral, neuropathic at level or neuropathic below level pain in the surgical and non-surgical groups at any stage. The results from this study suggest that apart from an increased prevalence of musculoskeletal pain at 2 weeks following SCI in those who undergo surgery, there is no significant relationship between surgical intervention and the presence of SCI pain.

OBJECTIVE To determine the outcome of patients with subarachnoid haemorrhage and whether delays in their diagnosis and referral have been reduced over a 15-year period. DESIGN A 15-year retrospective study of patients admitted to a tertiary neurosurgical unit between 1977 and 1992. SETTING The Royal North Shore Hospital, Sydney. PATIENTS 511 patients admitted with subarachnoid haemorrhage from ruptured intracranial aneurysms. RESULTS Of 486 patients with at least a six-month follow-up, 66% made a good recovery and 19% died. Outcome was significantly influenced by the neurological condition of the patient at admission (P < 0.0001). There was no significant difference in the relative proportions of patients transferred late (three or more days after onset of symptoms) when those admitted before and after 1986 were compared. CONCLUSION Delayed diagnosis and referral remain the major preventable problems in the management of patients with aneurysmal subarachnoid haemorrhage.