Marlon Perera

Sensitivity, Specificity, and Predictors of Positive 68Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT Positron emission tomography (PET) of 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality introduced to assess the burden of prostate cancer, typically in biochemically recurrent or advanced disease. 68Ga-PSMA PET provides the ability to selectively identify and localize metastatic prostate cancer cells and subsequently change patient management. Owing to its limited history, robust sensitivity and specificity data are not available for 68Ga-PSMA PET-positive scans. OBJECTIVE A systematic review and meta-analysis of reported predictors of positive 68Ga-PSMA PET and corresponding sensitivity and specificity profiles. EVIDENCE ACQUISITION We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analysis and meta-regression of proportions were performed using a random-effects model with pre-PET prostate-specific antigen (PSA) levels as the dependent variable. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. EVIDENCE SYNTHESIS Sixteen articles involving 1309 patients were analysed. The overall percentage of positive 68Ga-PSMA PET among patients was 40% (95% confidence interval [CI] 19-64%) for primary staging and 76% (95% CI 66-85%) for biochemical recurrence (BCR). Positive 68Ga-PSMA PET scans for BCR patients increased with pre-PET PSA. For the PSA categories 0-0.2, 0.2-1, 1-2, and >2 ng/ml, 42%, 58%, 76%, and 95% scans, respectively, were positive. Shorter PSA doubling time increased 68Ga-PSMA PET positivity. On per-patient analysis, the summary sensitivity and specificity were both 86%. On per-lesion analysis, the summary sensitivity and specificity were 80% and 97%, respectively. CONCLUSIONS In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive 68Ga-PSMA PET. Pooled data indicate favourable sensitivity and specificity profiles compared to choline-based PET imaging techniques. PATIENT SUMMARY Positron emission tomography using 68Ga-labelled prostate-specific membrane antigen is an emerging radiological technique developed to improve the characterisation of metastatic prostate cancer. We summarised the data available to date and found that this new test provides excellent rates of detection of cancer spread in late-stage prostate cancer.

Prostatic Urethral Lift Improves Urinary Symptoms and Flow While Preserving Sexual Function for Men with Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis

CONTEXT Treatment for lower urinary tract symptoms resulting from benign prostatic hyperplasia (BPH) is varied, and significant side effects, particularly concerning sexual function, affect uptake. The prostatic urethral lift (PUL) procedure is a recent addition to the armamentarium for BPH treatment, with independent reports suggesting improvement of symptoms, sexual function, and urinary flow. OBJECTIVE We undertook a systematic review and meta-analysis of reported symptomatic, functional, and sexual outcomes following the PUL procedure. EVIDENCE ACQUISITION We performed a critical review of Medline, Embase, ScienceDirect, Cochrane Library, and Web of Science databases in May 2014 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Quality assessment was performed using a modification of the Methodological Index for Non-Randomized Studies tool. All retrospective, prospective, and controlled trials were included for analysis. Symptom scores, sexual health scores, and functional outcomes were pooled and meta-analysed using quality and random-effects models. EVIDENCE SYNTHESIS Ten articles comprising six independent patient cohorts were included for analysis. Pooled estimates from between 452 and 680 patients suggested overall improvement following PUL, including symptoms (large gain; standardised mean gain range of 1.3-1.6, International Prostate Symptom Score difference of -7.2 to -8.7 points), maximum flow rate (3.8-4.0 ml/s), and quality of life (2.2-2.4 points). Sexual function was preserved with a small improvement estimated at 12 mo (standardised mean gain range of 0.3-0.4). Pooled estimates were mostly heterogeneous across study groups. CONCLUSIONS PUL is a well-tolerated, minimally invasive therapy for BPH that provides favourable symptom, sexual health, and functional outcomes during follow-up to 12 mo. Longer follow-up and larger randomised studies are required to further confirm these preliminary results. PATIENT SUMMARY We reviewed the early results of an innovative procedure directed towards the management of prostate enlargement. The results revealed a well-tolerated procedure that produces improvement in urinary symptoms and function while preserving sexual function.

Globalization of Continuing Professional Development by Journal Clubs via Microblogging: A Systematic Review

Background Journal clubs are an essential tool in promoting clinical evidence-based medical education to all medical and allied health professionals. Twitter represents a public, microblogging forum that can facilitate traditional journal club requirements, while also reaching a global audience, and participation for discussion with study authors and colleagues. Objective The aim of the current study was to evaluate the current state of social media–facilitated journal clubs, specifically Twitter, as an example of continuing professional development. Methods A systematic review of literature databases (Medline, Embase, CINAHL, Web of Science, ERIC via ProQuest) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of Twitter, the followers of identified journal clubs, and Symplur was also performed. Demographic and monthly tweet data were extracted from Twitter and Symplur. All manuscripts related to Twitter-based journal clubs were included. Statistical analyses were performed in MS Excel and STATA. Results From a total of 469 citations, 11 manuscripts were included and referred to five Twitter-based journal clubs (#ALiEMJC, #BlueJC, #ebnjc, #urojc, #meded). A Twitter-based journal club search yielded 34 potential hashtags/accounts, of which 24 were included in the final analysis. The median duration of activity was 11.75 (interquartile range [IQR] 19.9, SD 10.9) months, with 7 now inactive. The median number of followers and participants was 374 (IQR 574) and 157 (IQR 272), respectively. An overall increasing establishment of active Twitter-based journal clubs was observed, resulting in an exponential increase in total cumulative tweets (R 2=.98), and tweets per month (R 2=.72). Cumulative tweets for specific journal clubs increased linearly, with @ADC_JC, @EBNursingBMJ, @igsjc, @iurojc, and @NephJC, and showing greatest rate of change, as well as total impressions per month since establishment. An average of two tweets per month was estimated for the majority of participants, while the “Top 10” tweeters for @iurojc showed a significantly lower contribution to overall tweets for each month (P<.005). A linearly increasing impression:tweet ratio was observed for the top five journal clubs. Conclusions Twitter-based journal clubs are free, time-efficient, and publicly accessible means to facilitate international discussions regarding clinically important evidence-based research.

Prostate cancer biomarkers: Are we hitting the mark?

Purpose Localised prostate cancer diagnosis and management is increasingly complex due to its heterogeneous progression and prognostic subgroups. Pitfalls in current screening and diagnosis have prompted the search for accurate and invasive molecular and genetic biomarkers for prostate cancer. Such tools may be able to distinguish clinically significant cancers from less aggressive variants to assist with prostate cancer risk stratification and guide decisions and healthcare algorithms. We aimed to provide a comprehensive review of the current prostate cancer biomarkers available and in development. Methods MEDLINE and EMBASE databases searches were conducted to identify articles pertaining to the use of novel biomarkers for prostate cancer. Results A growing number of novel biomarkers are currently under investigation. Such markers include urinary biomarkers, serology-based markers or pathological tissue assessments of molecular and genetic markers. While limited clinical data is present for analysis, early results appear promising. Specifically, a combination of serum and urinary biomarkers (Serum PSA + Urinary PCA3 + Urinary TMPRSS2-ERG fusion) appears to provide superior sensitivity and specificity profiles compared to traditional diagnostic approaches (AUC 0.88). Conclusion The accurate diagnosis and risk stratification of prostate cancer is critical to ensure appropriate intervention. The development of non-invasive biomarkers can add to the information provided by current screening practices and allows for individualised risk stratification of patients. The use of these biomarkers appears to increase the sensitivity and specificity of diagnosis of prostate cancer. Further studies are necessary to define the appropriate use and time points of each biomarker and their effect on the management algorithm of prostate cancer.

Long-Term Urethral Function Measured by Uroflowmetry After Hypospadias Surgery: Comparison with an Age Matched Control

PURPOSE Long-term outcomes of hypospadias surgery, particularly urinary function, have not been examined thoroughly. Uroflowmetry can be used to evaluate long-term functional outcomes by assessing flow shape and the rate of micturition. We assessed urethral function using uroflowmetry in adolescents after undergoing hypospadias repair in infancy and compared this with age matched controls. MATERIALS AND METHODS After human research ethics committee approval (HREC 28111A), 17 boys 13 to 15 years old with no history of urological or neurological disorders underwent uroflowmetry (65 separate voids) to determine standard values for boys of this age. Then 60 boys age 13 to 15 years who had undergone treatment for hypospadias in early infancy were seen for long-term followup and underwent uroflow assessment. RESULTS Standard urinary flow rates were established in the 13 to 15-year-old control group and represented on a nomogram. In the boys who underwent hypospadias surgery the urine flow rates were significantly lower compared to the control nomogram (p <0.0001), with half the patients having uroflow rates below 1 SD from the control mean but without symptoms. Boys with significant preoperative chordee were more likely to have poorer urinary flow (p <0.04). A poor urinary flow rate also was significantly associated with post-void residual bladder volume (p <0.03). There was no correlation with original meatal location, number of operations, presence of postoperative complications, current anatomy and lower urinary tract symptoms (eg post-void dribble, hesitancy, incontinence). CONCLUSIONS At long-term followup after hypospadias surgery urinary flow rates were significantly lower compared to age matched controls but still fell within the normal range. In the hypospadias cohort there was no significant association with lower urinary tract symptoms and poor urinary flow. Detection of poor urinary flow may indicate incomplete bladder emptying. The presence of severe chordee preoperatively is a significant risk factor for poor urinary flow rates on long-term followup.

An update on focal therapy for prostate cancer

Globally, the increased uptake of serum PSA level screening led to an increase in the number of diagnoses of low-risk and intermediate-risk prostate cancer. Traditionally, these patients have been considered for either active surveillance programmes or radical whole-gland therapies, such as prostatectomy or radiotherapy. Focal therapy is an emerging treatment option that involves the focal ablation of prostate cancer with preservation of surrounding healthy tissue. This approach might result in reduced morbidity when compared with whole-gland therapies. In current practice, much controversy surrounds optimal patient selection and preoperative tumour localization strategies. Focal therapy modalities include cryotherapy, high-intensity focused ultrasound, laser ablation, photodynamic therapy, irreversible electroporation, radiofrequency ablation and focal brachytherapy. However, as long-term oncological data for focal therapies are lacking, formal recommendations for its use cannot be made.

Clearing emergency departments and clogging wards: National Emergency Access Target and the law of unintended consequences

To assess ED length of stay (EDLOS), access block, inpatient length of stay (IPLOS) and waiting times before and after the implementation of the National Emergency Access Target (NEAT).

Comparison of contemporary methods for estimating prostate tumour volume in pathological specimens

To evaluate the accuracy of various prostate tumour volume (TV) estimation methods.

A systematic review of patient-related risk factors for catheter-related thrombosis

Abstract To identify patient-related risk factors for venous thrombosis in patients with central venous catheters (CVC) or peripherally inserted central catheters (PICC). We performed a systematic review of the literature assessing patient-related risk factors for thrombosis related to CVC or PICC. The databases PubMed, Ovid and the Cochrane library were searched for observational studies pertaining to patient-related risk factors for CVC and PICC-related thrombosis. The initial search through PubMed, Ovid and the Cochrane library yielded 516 results. After 71 duplicates were removed, 445 articles were assessed for eligibility based on title and abstract. Four hundred and eleven articles were then excluded and 33 full text articles were manually assessed for eligibility. Eight articles were eliminated as they did not contain content relevant to the review. Twenty-five studies were then selected to assess 20 risk factors. There were no consistent significant associations for catheter-related thrombosis across the twenty-five studies. Multiple studies identified age, malignancy, diabetes, obesity, chemotherapy, thrombophilia and a history of thrombosis as significant risk factors for catheter-related thrombosis. Inconsistent findings among studies make it difficult to establish which patient-related risk factors are associated with catheter-related thrombosis. Future studies could include larger sample sizes and more cases of catheter-related thrombosis to produce more significant results. Identification of patient-related risk factors could lead to early recognition of upper limb deep vein thrombosis in patients with catheters, thereby preventing complications.

Penile Cancer: Contemporary Lymph Node Management

Purpose: In penile cancer, the optimal diagnostics and management of metastatic lymph nodes are not clear. Advances in minimally invasive staging, including dynamic sentinel lymph node biopsy, have widened the diagnostic repertoire of the urologist. We aimed to provide an objective update of the recent trends in the management of penile squamous cell carcinoma, and inguinal and pelvic lymph node metastases. Materials and Methods: We systematically reviewed several medical databases, including the Web of Science® (with MEDLINE®), Embase® and Cochrane databases, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta‐Analyses) guidelines. The search terms used were penile cancer, lymph node, sentinel node, minimally invasive, surgery and outcomes, alone and in combination. Articles pertaining to the management of lymph nodes in penile cancer were reviewed, including original research, reviews and clinical guidelines published between 1980 and 2016. Results: Accurate and minimally invasive lymph node staging is of the utmost importance in the surgical management of penile squamous cell carcinoma. In patients with clinically node negative disease, a growing body of evidence supports the use of sentinel lymph node biopsies. Dynamic sentinel lymph node biopsy exposes the patient to minimal risk, and results in superior sensitivity and specificity profiles compared to alternate nodal staging techniques. In the presence of locoregional disease, improvements in inguinal or pelvic lymphadenectomy have reduced morbidity and improved oncologic outcomes. A multimodal approach of chemotherapy and surgery has demonstrated a survival benefit for patients with advanced disease. Conclusions: Recent developments in lymph node management have occurred in penile cancer, such as minimally invasive lymph node diagnosis and intervention strategies. These advances have been met with a degree of controversy in the contemporary literature. Current data suggest that dynamic sentinel lymph node biopsy provides excellent sensitivity and specificity for detecting lymph node metastases. More robust long‐term data on multicenter patient cohorts are required to determine the optimal management of lymph nodes in penile cancer.