Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis.

BACKGROUND: Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy. OBJECTIVE: We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis. METHODS: We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI). RESULTS: We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78-3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23-4.62), tamoxifen (SMD - 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD - 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44-2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo. CONCLUSION: There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men. PROSPERO: CRD42023430179.

Erectile dysfunction: Is platelet-rich plasma the new frontier for treatment in patients with erectile dysfunction? A review of the existing evidence.

Erectile dysfunction (ED) is one of the commonest disorders in adult males and affects 12-19% of men of reproductive age. Only few studies have evaluated the impact of ED on men and couples with infertility-these studies report higher rates of ED in this sub-group of men compared to the general population, with the prevalence of ED in men diagnosed with male infertility ranging from 6.7 to 61.6%. Nevertheless, ED is considered a rare cause of male infertility, accounting for about 0.4-5% of all causes of male infertility. ED remains a poorly treated condition globally and current therapies, like oral medication, offer only temporary symptomatic relief and do not influence disease progression-patients are potentially on lifelong treatment, with ED worsening over time. In contrast, regenerative medicine may potentially reverse or halt the progression of ED processes. In this article, we review the evidence for intracavernosal injections of platelet-rich plasma (PRP) in the treatment of ED.

Penile Mass: When Should Someone Worry and Seek Care?

OBJECTIVES: We present a summary of penile cancer, its epidemiology, risk factors, and possible clinical presentations. We discuss a range of penile lesions that indicate an underlying penile malignancy. We also consider some nonmalignant penile lesions that may be confused with penile cancer. DATA SOURCES: Sources of information include original research articles, review journal articles, and textbooks, which have been referenced in the article. CONCLUSION: Penile cancer is a rare disease, although geographical variations exist. Due to this rarity, many health care professionals may overlook a diagnosis of penile cancer. Malignant penile lesions may often be confused with benign lesions and vice versa. One needs to have a high index of suspicion to not overlook this important diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Referral to specialists should be made if malignancy is suspected, if the diagnosis is uncertain, or if the lesion persists despite reasonable treatment with steroids and other creams.

Update on penile sparing surgery for penile cancer.

PURPOSE OF REVIEW: Penile sparing surgery (PSS) is considered the standard of care in penile cancer where appropriate, as preservation of the penis may enable the patient to maintain urinary and sexual function. This review will focus on the latest developments over the past two years. RECENT FINDINGS: In this review, we discuss the latest findings in oncological outcomes in PSS, specifically glansectomy. We also introduce technology that may be useful in improving the precision of surgical resection margins in PSS. Finally, we consider the value of patient-reported outcome measures (PROMs) and consider how research in this area can be improved. SUMMARY: A recent study has found a correlation between local recurrences (LR) and worse overall and cancer-specific survival in glansectomy, which challenges the belief that LR do not confer worse oncological outcomes. Despite numerous studies evaluating PROMs in penile cancer/PSS, few of these studies provide quality evidence of the 'supportive care needs'. A shift in research is required to identify those men at most risk of distress and to identify ways to support men diagnosed with penile cancer.

An unusual case of asymptomatic non-urothelial bladder tumour.

INTRODUCTION: Non-urothelial tumours are rare and account for less than 5% of all bladder tumours. Bladder paragangliomas also known as extra-adrenal pheochromocytomas are of the non-urothelial subgroup. We present an unusual case of asymptomatic bladder paraganglioma. CASE REPORT: A 77year old lady presented with acute abdominal pain was found to have an incidental enhancing nodule in the bladder. During cystoscopy and transurethral resection the patient experienced significant fluctuations in blood pressure that required anaesthetic adjustments. Review of histology confirmed a diagnosis of bladder paraganglioma. DISCUSSION: Most bladder paraganglioma cases present with sympathomimetic related symptoms and microscopic haematuria but our patient was asymptomatic which resulted in inadequate pre-operative optimisation and high anaesthetic risk. Majority of paragangliomas are benign but there is a 20-40% chance of malignancy. The management options will predominantly depend on whether disease is localised, regional, metastatic or recurrent in nature. CONCLUSION: Due to the non-specific nature of disease, variability of presentations and rare incidence, bladder paragangliomas are often not part of the urologists' differential diagnoses. In our opinion, establishing guidelines should assist to achieve a balance between anaesthetic risks, cystoscopy and follow up.

Open partial nephrectomy in renal cell cancer - Essential or obsolete?

Since the first partial nephrectomy was first conducted 131 years ago, the procedure has evolved into the gold standard treatment for small renal masses. Over the past decade, with the introduction of minimally invasive surgery, open partial nephrectomy still retains a valuable role in the treatment of complex tumours in challenging clinical situations (e.g. hereditary renal cancer or single kidneys), and enables surgeons to push the boundaries of nephron-sparing surgery. In this article, we consider the origin of the procedure and how it has evolved over the past century, the surgical techniques involved, and the oncological and functional outcomes.

What Burden of Prostate Cancer Can Radiologists Rule Out on Multiparametric Magnetic Resonance Imaging? A Sensitivity Analysis Based on Varying the Target Condition in Template Prostate Mapping Biopsies.

OBJECTIVE: To evaluate the minimum disease burden of prostate cancer at which multiparametric magnetic resonance imaging (MRI) optimally performs. METHODS: Between 2006 and 2008, 64 men underwent multiparametric MRI imaging (index test) followed by template prostate mapping biopsy (reference test). Three radiologists independently reported each quadrant of every prostate on a scale of 1 to 5: highly likely benign, likely benign, equivocal, likely malignant, highly likely malignant (≥3 or ≥4 was considered positive). There were 256 prostate sectors; bootstrapping adjustment was used to account for nonindependence. The target condition indicating cancer on biopsies was varied by changing the maximum cancer core length (MCCL) and total cancer core length (TCCL) within each sector from 1 mm to 10 mm. The sensitivity, specificity, and positive (PPVs) and negative predictive values (PPVs) were calculated for each MCCL and TCCL. Gleason ≤3+3 and Gleason ≥3+4 cancers were analyzed separately. RESULTS: Mean age was 62 years (range, 40-76 years), and mean prostate-specific antigen level was 8.2 µg/L (range, 2.1-43 µg/L). Fifty percent of quadrants (127 of 256) had prostate cancer, of which 65% (83 of 127) were Gleason ≤3+3. For Gleason ≤3+3, multiparametric MRI had an NPV of ≥95% at an MCCL of ≥5 mm and at a TCCL of ≥7 mm (MRI score ≥3). For Gleason ≥3+4, an NPV of ≥95% was seen at an MCCL of ≥5 mm (MRI score ≥3) and TCCL ≥6 mm. CONCLUSION: Multiparametric MRI may allow areas of the prostate which test negative to avoid biopsy. Whether multiparametric MRI can be used as a "triage" test before the first biopsy requires results from ongoing prospective validating cohort studies.

Hospital admissions after transrectal ultrasound-guided biopsy of the prostate in men diagnosed with prostate cancer: a database analysis in England.

OBJECTIVES: To investigate the complication rate within 30 days after transrectal ultrasound-guided biopsy of the prostate in England, and to examine associated risk factors. METHODS: A population-based study was carried out using the English cancer registry linked to administrative hospital data. We included men aged 45 years and older diagnosed with prostate cancer between 2000 and 2008. A complication was considered to have occurred if men had been admitted to hospital as a result of urological causes (urinary tract infection/sepsis, hematuria and urinary retention) within 30 days of the transrectal ultrasound-guided biopsy of the prostate. Multivariable logistic regression was carried out to estimate odds ratios, reflecting the impact of risk factors on the complication rate. RESULTS: Of the 198,361 included men, 69% were aged between 65 and 84 years. The 30-day complication rate was 3.7% (1.1% for urinary tract infection/sepsis, 1.4% for hematuria and 1.3% for urinary retention). The most important risk factors were age above 85 years (odds ratio 3.85, 95% confidence interval 3.18-4.67, compared with age below 55 years) and three or more comorbidities (odds ratio 3.50, 95% confidence interval 3.17-5.87, compared with no comorbidity). The overall complication rate increased over time (odds ratio 1.20, 95% confidence interval 1.08-1.34, 2008 compared with 2000), as did the complication rate as a result of urinary tract infection/sepsis (odds ratio 1.72, 95% confidence interval 1.41-2.10, 2008 compared with 2000). CONCLUSIONS: There has been an increase in the complication rate after transrectal ultrasound-guided biopsy of the prostate in England between 2000 and 2008, predominantly as a result of infections. Age and comorbid conditions seem to represent the two most important risk factors for occurrence of post-biopsy complications.

The accuracy of multiparametric MRI in men with negative biopsy and elevated PSA level--can it rule out clinically significant prostate cancer?

PURPOSE: To assess the performance of multiparametric magnetic resonance imaging (mp-MRI) in patients with previous negative transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS: Fifty-four patients with at least 1 previous negative TRUS prostate biopsy underwent mp-MRI in the form of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging. This was followed by transperineal template systematic prostate biopsies. Analysis was done based on 2 sectors per prostate, right and left (108 sectors out of 54 prostates). mp-MRI was scored using an ordinal scale 1 to 5 based on the suspicion of the presence of clinically significant disease. We used 6 different definitions for clinically significant disease and tested the performance of mp-MRI at each single definition. RESULTS: Median age was 64 (range, 39-75), median PSA level was 10 (range, 2-23), and median number of biopsies was 45 (range, 21-137). Cancer of any volume and any grade was detected in 34 of 54 (63%) patients. mp-MRI accuracy at detection of clinically significant cancer using University College London (UCL) definition 2 (any Gleason score of 4 or maximum cancer core length of ≥ 4 mm or both) showed sensitivity of 76%, specificity of 42%, positive predictive value of 38%, and negative predictive value of 79%. For a different definition of significant tumor (UCL definition 1; dominant Gleason score 4 or maximum cancer core length ≥ 6 mm or both), the sensitivity was 90%, specificity 42%, positive predictive value 26%, and negative predictive value 95%. CONCLUSIONS: mp-MRI showed good performance at both detection and ruling out clinically significant disease, according to the definition used. mp-MRI can then be used as a triage test in the population with persistently elevated or rising PSA levels to select patients that can avoid unnecessary prostate biopsy.