Do alpha blockers reduce the risk of urinary retention post-transperineal prostate biopsy? A systematic narrative review.

BACKGROUND: Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications associated with transrectal ultrasound-guided prostate biopsy (TRUSB). TPB is associated with an infective complication rate of near zero, however, acute urinary retention (AUR) remains the leading complication causing morbidity. Previously in TRUSB, there was weak evidence that alpha-blockers reduce AUR rates, and their usage has been extrapolated to clinical practice with TPB. This review aims to explore if there is an evidence base for using alpha-blockers to prevent AUR following TPB. METHODS: A systematic approach was used to search Ovid Medline and Embase using keywords related to "Transperineal" and "Retention". Articles were then screened by applying inclusion and exclusion criteria to find studies that compared alpha-blocker recipients to no alpha-blocker use in the perioperative period and the subsequent effect on AUR in TPB. RESULTS: 361 records were identified in the initial search to produce 5 studies included in the final review. No randomised controlled trials (RCTs) were identified. One observational study showed a reduction in AUR rate from 12.5% to 5.3% with a single dose of tamsulosin. A previous systematic review of complications associated with prostate biopsy concluded there may be a potential benefit to alpha-blockers given in the TPB perioperative period. Three observational studies demonstrated a harmful effect related to alpha-blocker use; however, this was well explained by their clear limitations. CONCLUSION: Based on this review and the extrapolation from TRUSB data, perioperative alpha-blockers may offer some weak benefits in preventing AUR following TPB. However, there is significant scope and need for an RCT to further develop the evidence base further given the significant gap in the literature and lack of a standard alpha blocker protocol in TPB.

PEDAL protocol: a prospective single-arm paired comparison of multiparametric MRI and 18F-DCPFyl PSMA PET/CT to diagnose prostate cancer.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy. METHODS AND ANALYSIS: The PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. Sample size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management. ETHICS AND DISSEMINATION: This study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute. TRIAL REGISTRATION NUMBER: ACTRN12620000261910.

Utility of urinary biomarkers in primary haematuria: Systematic review and meta-analysis.

Objectives: To evaluate the diagnostic performance of FDA-approved urinary biomarkers in the evaluation of primary haematuria for investigation of bladder cancer. Methods: The scientific databases MEDLINE, EMBASE, Pubmed and Web of Science were searched to collect studies. Studies that evaluated the diagnostic performance of FDA-approved urinary biomarkers in investigating patients with primary haematuria without a prior history of bladder cancer were included. Quality of studies was assessed using the JBI Criteria. Bivariate mixed-effects regression model was used to calculate pooled sensitivities and specificities for each biomarker. Results: Eighteen studies were included in the analysis. The biomarkers assessed in these studies were CxBladder, AssureMDx, Bladder Tumour Antigen (BTA), NMP22, UroVysion and Immunocyt/uCyt+. Several biomarkers, such as AssureMDx, CxBladder and Immunocyt, were shown to have better diagnostic performance based on their sensitivity, specificity and diagnostic odds ratio, as well as positive and negative likelihood ratios. Across the six biomarkers, sensitivity ranged from 0.659 to 0.973, and the specificity ranged between 0.577 and 0.833. Conclusion: Despite certain biomarkers demonstrated better performance, current diagnostic abilities of the FDA-approved biomarkers remain insufficient for their general application as a rule out test for bladder cancer diagnosis and as a triage test for cystoscopy in patients with primary haematuria. High-quality prospective studies are required to further analyse this and also analyse the correct scenario in which urinary biomarkers may be best utilised.

Thermo-expandable prostatic stents for bladder outlet obstruction in the frail and elderly population: An underutilized procedure?

Purpose: To report our outcomes with the use of a thermo-expandable metallic intraprostatic stent (Memokath) for patients with bladder outlet obstruction (BOO) secondary to prostatic obstruction, and to assess it is a feasible option for many frail and elderly men unsuitable for surgery. Materials and Methods: We reviewed patients who underwent insertion of a Memokath stent for BOO over 17 years (January 1999 to December 2015) at one regional center over a long follow-up period (median, 7 years). Patients were selected if they had obstructive urinary symptoms or urinary retention with an indwelling catheter in situ, and were ineligible for transurethral resection of the prostate (TURP) under general or spinal anesthesia. Primary outcomes assessed were the improvement in urinary symptoms and voiding parameters, as well as the ability to void spontaneously if catheterized, along with complications. Results: One hundred forty-four patients who presented with BOO or urinary retention had a Memokath stent inserted. Ninety patients (62.5%) had a successful stent insertion with a significant difference between the median preoperative (550 mL) and postoperative residual volume (80 mL, p<0.0001). Nearly two-thirds of men (64%) returned to unassisted voiding with no increased risk of complications over time. Fifty-four patients (37.5%) experienced stent failure. Main complications requiring stent removal or repositioning were migration, occlusion, refractory urinary retention and irritative voiding symptoms. Conclusions: In elderly and frail men with BOO deemed unsuitable to undergo TURP, prostatic stent is a safe and practical alternative to long-term catheterization.

Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent.

OBJECTIVES: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and chronic kidney disease. Two promising preconditioning methods for the kidney, intermittent arterial clamping (IC) and treatment with the hypoxia mimetic cobalt chloride, have never been directly compared. Furthermore, the protective efficacy of the chemically related transition metal Zn2+ against renal IRI is unclear. Although Co2+ ions have been shown to protect the kidney via hypoxia inducible factor (HIF), the effect of Zn2+ ions on the induction of HIF1α, HIF2α and HIF3α has not been investigated previously. MATERIALS AND METHODS: The efficacy of different preconditioning techniques was assessed using a Sprague-Dawley rat model of renal IRI. Induction of HIF proteins following Zn2+ treatment of the human kidney cell lines HK-2 (immortalized normal tubular cells) and ACHN (renal cancer) was measured using Western Blot. RESULTS: Following 40 minutes of renal ischemia in rats, cobalt preconditioning offered greater protection against renal IRI than IC as evidenced by lower peak serum creatinine and urea concentrations. ZnCl2 (10 mg/kg) significantly lowered the creatinine and urea concentrations compared to saline-treated control rats following a clinically relevant 60 minutes of ischemia. Zn2+ induced expression of HIF1α and HIF2α but not HIF3α in HK-2 and ACHN cells. CONCLUSION: ZnCl2 preconditioning protects against renal IRI in a dose-dependent manner. Further studies are warranted to determine the possible mechanisms involved, and to assess the benefit of ZnCl2 preconditioning for clinical applications.

Identification of binding sites for C-terminal pro-gastrin-releasing peptide (GRP)-derived peptides in renal cell carcinoma: a potential target for future therapy.

OBJECTIVE: To determine the expression and biology of the neuroendocrine growth factor gastrin-releasing peptide (GRP) and other proGRP-derived peptides in renal cancer. MATERIALS AND METHODS: Receptor binding studies, enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, were used to quantitate the presence of proGRP-derived peptide receptors and their ligands in renal cancer cell lines and human renal cancers. Biological activity of proGRP peptides was confirmed with proliferation, migration, and extracellular-signal-regulated kinases 1 and 2 (ERK1/2) activation assays in vitro. In vivo, ACHN renal cancer xenografts were treated with proGRP-derived peptides to assess tumour size and necrosis. hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor (VEGF) expression were investigated with Western blotting and ELISA respectively, to determine the possible contribution of the proGRP peptides to tumour viability. RESULTS: In ACHN cells that expressed both proGRP- and GRP-receptors, the expression of proGRP binding sites was 80-fold greater than the GRP-receptor (GRPR). C-terminal proGRP-derived peptides stimulated the activation of ERK1/2, but with a different time course to GRP, consistent with the suggestion that these peptides may have unique cellular functions. Both GRP and proGRP47-68 stimulated proliferation and migration of ACHN cells in vitro, but only GRP reduced the extent of tumour necrosis in ACHN xenografts. GRP, but not proGRP47-68, was able to induce HIF1α and VEGF expression in ACHN cells. This may account in part for the reduction in necrosis after GRP treatment. C-terminal proGRP-derived peptides were present in all three renal cancer cell lines and a panel of human renal cancers, but mature amidated GRP was absent. CONCLUSION: C-terminal proGRP peptides are more abundant in renal cancers and their cell lines than the more extensively studied amidated peptide, GRP. These results suggest that C-terminal proGRP-derived peptides may be a better target for novel renal cancer treatments.

Algorithm for selecting men for pelvic lymph node dissection (PLND) during radical prostatectomy based on clinical risk factors in an Australian population.

OBJECTIVE: To define selection criteria for pelvic lymph node dissection (PLND) based on a contemporary Australian cohort of men with clinically localised prostate cancer undergoing radical prostatectomy (RP) with PLND, as stage migration of prostate cancer has led to re-evaluation of the role of PLND at the time of RP. PATIENTS AND METHODS: In all, 200 consecutive men treated by one surgeon between 2000 and 2005 with open RP and PLND. The clinical and pathological data were extracted by retrospective chart review. Associations between clinical predictors and LN positivity were assessed by logistic regression analysis. RESULTS: Overall, there were LN metastases were in 10 (5%) men. The LN positivity rate was significantly associated with biopsy Gleason score, preoperative prostate-specific antigen (PSA) concentration and percentage of positive cores (PPC), with respective odds ratios (OR) (95% confidence interval [CI]) of 3.70 (1.98-6.92), 1.11 (1.04-1.19) and 1.04 (1.01-1.06) Trend toward significant association with clinical stage (OR 1.75, 95% CI 0.97-3.13) On multivariate analysis, PSA concentration and biopsy Gleason score were significant predictors of LN disease. All 10 men with LN metastases came from a high-risk group of 96, identifiable by having at least one of the following: stage ≥ cT2b, biopsy Gleason score ≥ 4+3, PSA concentration of ≥ 10 ng/mL or PPC of ≥ 38%. CONCLUSIONS: The risk of LN metastases depends upon well-defined clinical risk factors of stage, biopsy Gleason score, PSA concentration and PPC. The present data suggests a simple risk-stratification method, using these risk factors, of identifying men to have PLND at the time of RP.

Predictors of positive surgical margins at open and robot-assisted laparoscopic radical prostatectomy: a single surgeon series.

Robot-assisted laparoscopic radical prostatectomy (RALRP), increasingly used to treat localized prostate cancer, has advantages over open radical prostatectomy (ORP) in terms of reduced bleeding and quicker convalescence. However, debate continues over whether RALRP provides superior or at least equivalent surgical outcomes. This study compares positive surgical margins (+SM), as a surrogate for long-term cancer control, at RALRP and ORP performed by a single experienced surgeon during the process of taking up RALRP. 400 consecutive patients undergoing surgery for prostate cancer under a single surgeon (DW) between November 1999 and July 2009 were studied. Prior to July 2005, all patients underwent ORP; after this date, most patients were treated by RALRP. Data were collected by retrospective chart review and analysed independently of the treating surgeon. +SM were defined as the presence of cancer at an inked surface. Overall, 23 (11.5%) of 200 patients undergoing RALRP had +SM, compared to 40 (20.0%) of 200 patients undergoing ORP (P < 0.05). On univariate logistic regression analysis, in addition to surgical approach (odds ratio [OR] = 1.92), patient age (OR = 1.05), pathologic stage (OR = 3.93) and specimen Gleason (GS) score (OR = 1.86) were significant predictors of +SM. On multivariate analysis, surgical approach, p-stage and specimen GS remained significant predictors of +SM. RALRP is associated with lower rates of +SM compared to ORP, even after adjusting for other known risk factors. Of note, the RALRP in this study were part of the surgeon's learning curve.

Paraneoplastic movement disorders.

Neurologic paraneoplastic syndromes (NPSs) result from damage to the nervous system due to the remote effects of cancer not related to metastasis, infection, or metabolic derangements. NPSs are rare, affecting 1 in 10,000 patients with cancer. Pathogenesis is likely related to the immune mechanisms: normal neural tissue is mistakenly attacked due to the similarity in the onconeural antigens expressed by the tumor cells. Among the various "classic" and other NPSs, this review focuses on paraneoplastic movement disorders, including ataxia due to cerebellar degeneration, stiff-person syndrome, opsoclonus-myoclonus syndrome, chorea, parkinsonism, and tremor. The recently described syndrome of paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis is also included, given that these patients have complex movements such as stereotypies and dyskinesias in addition to psychiatric symptoms, altered sensorium, and other neurologic signs. Although variable, treatment and prognosis of NPSs rely heavily on treatment of the underlying malignancy and immunotherapy.

Diagnosis of pheochromocytoma in the setting of Parkinson disease.

BACKGROUND: A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. DIAGNOSIS: Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.

An analysis of the causes of bladder neck contracture after open and robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: To evaluate the difference in outcome of bladder neck contracture (BNC) and its causes between large groups of patients undergoing open radical prostatectomy (ORP) and robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: We analysed 200 consecutive RPs performed by one surgeon for prostate cancer, 100 by ORP and 100 by RALP, between March 2003 and September 2007. The operative techniques of bladder neck repair and urethro-vesical anastomosis were different. The ORP patients had a conventional stomatization and 'racquet handle' repair of the bladder if necessary, with mucosal eversion and a direct circular interrupted 'end-to-end' suture anastomosis between the bladder and urethra. The RALP patients had no bladder neck reconstruction or mucosal eversion and their anastomosis was by the continuous suture 'parachute' technique. RESULTS: There was no BNC in the RALP group, whilst 9% of the ORP group developed a BNC (P < 0.005). Apart from surgical technique, other variables, including patient age, previous transurethral resection of the prostate, Gleason score, T stage, urine infection rate, urinary leakage, blood loss, drain tube removal, anastomotic suture material, catheter type and catheter removal times were statistically comparable in both groups. CONCLUSION: This series suggests that the major factor involved in the cause of bladder neck contracture after ORP, relates to the stomatization or 'racquet handle' bladder neck repair, and the end-to-end anastomosis between the urethra and stomatized bladder. Mucosal eversion might also contribute. Normal postoperative urinary leakage when the anastomotic apposition is good seems unlikely to be a significant aetiological factor in the development of BNC. Prolonged urinary leakage results from an anastomotic gap, which heals by second intention, thereby causing scarring and BNC. The RALP 'parachute' technique, which expands the anastomosis towards the bladder, appears to protect against BNC. Mucosal eversion is not necessary in the parachute repair.

Selegiline orally disintegrating tablets in patients with Parkinson disease and "wearing off" symptoms.

BACKGROUND: Selegiline orally disintegrating tablet (ODT; Zelapar) is a selective monoamine oxidase B inhibitor developed as an adjunct to levodopa (LD) for Parkinson disease. Most patients on long-term LD therapy eventually experience deterioration at the end of the LD dosing interval, with predictable "wearing off" and "on-off" fluctuations. METHODS: We conducted a 12-week, double-blind, placebo-controlled, parallel-design trial of selegiline ODT. The primary efficacy point was reduction in the percentage of average daily "off" time. Secondary measures included reductions in daily off hours and total daily off time, Clinical Global Impressions-Improvement (CGI-I), and Patient Global Impression-Improvement (PGI-I). Patients on LD received selegiline ODT (1.25 mg/d for 6 weeks, then 2.5 mg/d for 6 weeks) or placebo. Safety and tolerability were measured. RESULTS: The intent-to-treat population included 98 patients receiving selegiline ODT and 50 patients receiving placebo. Combined efficacy results for weeks 10 and 12 revealed an 11.6% reduction in percentage of daily off time for selegiline ODT versus a 9.8% reduction for placebo (NS). PGI-I detected a statistically significant difference between treatment groups in favor of selegiline ODT (P = 0.02), whereas CGI-I detected a strong trend toward improvement (P = 0.06). Selegiline ODT was safe and well tolerated. CONCLUSIONS: This study showed no significant difference in improvement in percentage of off time with selegiline ODT versus placebo. Some clinical impressions (e.g., PGI-I, CGI-I) improved. This result contrasts with an identically designed study that showed a significant improvement in off time with selegiline ODT. A combined analysis of both studies suggested overall efficacy.

Paroxysmal Kinesigenic Segmental Myoclonus due to a spinal cord glioma.

We report an 18-year-old man with paroxysmal jerking movements of the left arm since age 7 years. These were invariably precipitated by startle or sudden movements. He was subsequently diagnosed with a cervical cord anaplastic astrocytoma on MRI. We could not identify previous reports of paroxysmal myoclonus secondary to a spinal cord neoplasm. We have coined the term Paroxysmal Kinesigenic Segmental Myoclonus to describe this entity.

Benefits and risks of pharmacological treatments for essential tremor.

Essential tremor can cause significant functional disability in some patients. The arms are the most common body part affected and cause the most functional disability. The treatment of essential tremor includes medications, surgical options and other forms of therapy. Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor. Treatment for essential tremor is recommended if the tremor causes functional disability. If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability. The currently available medications can improve tremor in approximately 50% of the patients. If the tremor is disabling, treatment should be initiated with either primidone or propranolol. If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination. If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used. If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit. Other medications that may be helpful include gabapentin or topiramate. If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor. Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used. There are other medications that have been tried in essential tremor and have questionable efficacy. These drugs include carbonic anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine. If the patient still has disabling tremor after medication trials, surgical options are usually considered. Surgical options include thalamotomy and deep brain stimulation of the thalamus. These surgical options provide adequate tremor control in approximately 90% of the patients. Surgical morbidity and mortality for these procedures is low. Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation. In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures. The use of medication and/or surgery can provide adequate tremor control in the majority of the patients.