Comparing T2-T3 staging of penile cancer according to the American Joint Committee on cancer 8th edition with two modified staging systems in predicting survival outcome: A single-center experience.

Introduction: Penile cancer is a rare malignancy of the genitourinary tract. We aimed to validate the recent changes in the T2 and T3 stages of penile cancer in the American Joint Committee on Cancer (AJCC) 8th edition and to compare its predictive ability with two other modified staging systems for survival outcomes. Methods: This is a retrospective study of patients diagnosed with penile cancer from June 2015 to March 2020. The AJCC 8th edition and two other newly proposed systems by Li et al. and Sali et al. were used for staging the tumor. All variables were categorized and correlated with lymph node (LN) metastases and overall survival (OS). Results: Fifty-four patients were eligible for this study. The mean age was 58 years (range 46-72 years). The tumor stage (P = 0.016), clinical LN stage (P = 0.001), the involvement of the spongiosa (P = 0.015) and the cavernosa (P = 0.002), lymphovascular invasion (LVI) (P = 0.000), and PNI (P = 0.021) were found to be the significant predictors of LN metastases. When the 5 year OS was compared between the T2 and T3 stages of the AJCC 8th edition, Li staging and the Sali staging systems, it was 91% and 50.1% (P = 0.001), 97.5% and 10.3% (P = 0.000), 94.4% and 14.7% (P = 0.000), respectively. The presence of LVI (P = 0.001) was the most significant independent predictor of OS. Conclusions: The recent changes in the AJCC 8th edition pertaining to the T2-T3 stage are relevant, although the other two newly proposed staging systems were more precise in predicting the survival outcomes.

Use of Anabolic-Androgenic Steroids and Male Fertility: A Systematic Review and Meta-analysis.

Background: Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive athletes, but many amateur men. Objective: The objective of this study was to assess and systematically review the effects of AAS on male fertility parameters, spermiogram, testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) and to review reversibility and other morbidity impacting fertility. Methods: Eligibility criteria - We included studies mentioning data about adult males using supraphysiologic doses of AAS for sports performance or appearance enhancement, with comparison data from general population or matched controls if available reporting fertility parameters and sexual performance. Information sources - A systematic literature search was performed using PubMed, MEDLINE, EMBASE, Google Scholar and World of Science. Controlled clinical trials randomised or nonrandomised (if available), case series with or without matched controls, case reports, cross-sectional surveys, reports on follow-up of subjects caught in doping test and their fertility parameters when reported. Risk of bias/quality assessment - The quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Results: Included studies - Thirty-two studies were included. There were 12 cohort studies, 5 case-control studies, 9 cross-sectional surveys and 6 case reports. The study population comprised 9371 individuals, of which 2671 were AAS users. Synthesis of results - AAS users had reduced levels of FSH and LH than the naïve population. These levels remained low for 3-6 months after stopping AAS. One year after stopping AAS, the users and naïve population had insignificant differences in FSH and LH values. The total testosterone (TT) levels were comparable in users and naïve populations at baseline, 3 months and 6 months after stopping, but at 1 year, TT values were lower in AAS users. Sperm concentration in AAS users and naïve population was similar, but sperm motility was lower in AAS users. The testicular size was lower in AAS users. The erectile function improved with AAS use, but on withdrawal, there was decreased libido and erectile dysfunction. Most AAS users need additional medications to mitigate detrimental effects on fertility. Description of the effect - AAS use negatively impacted the gonadotrophin levels and had lower sperm motility and testicular size. Strength - Comprehensive review of 32 publications, study population of 9371 individuals, of which 2671 were AAS users, meta-analysis of reproductive hormones, semen parameters and testis size. Limitations: The limitations are small sample size of most of the studies, polypharmacy, lack of information on dosing and high heterogeneity. Interpretation: AAS use is detrimental for sperm motility and has a partially reversible negative impact on male fertility. Users must be cautioned about its negative impact on libido and erectile function.Registration: PROSPERO Registration No. CRD42023411294.

Role of Macroscopic Image Enhancement in Diagnosis of Non-Muscle-Invasive Bladder Cancer: An Analytical Review.

Early diagnosis of non-muscle-invasive bladder cancer (NMIBC) is of paramount importance to prevent morbidity and mortality due to bladder cancer. Although white light imaging (WLI) cystoscopy has long been considered the gold standard in the diagnosis of bladder cancer, it can miss lesions in a substantial percentage of patients and is very likely to miss carcinoma in situ and dysplasia. Tumor margin detection by WLI can be inaccurate. Moreover, WLI could, sometimes, be inadequate in distinguishing inflammation and malignancy. To improve the diagnostic efficacy of cystoscopy, various optical image enhancement modalities have been studied. These image enhancement modalities have been classified as macroscopic, microscopic, or molecular. Photodynamic diagnosis (PDD), narrow band imaging (NBI), and Storz image 1 S enhancement (formerly known as SPIES) are macroscopic image enhancement modalities. A relevant search was performed for literature describing macroscopic image enhancement modalities like PDD, NBI, and image 1 S enhancement. The advantages, limitations, and usefulness of each of these in the diagnosis of bladder cancer were studied. Photodynamic diagnosis requires intravesical instillation of a photosensitizing agent and a special blue light cystoscope system. PDD has been shown to be more sensitive than WLI in the detection of bladder cancer. It is superior to WLI in the detection of flat lesions. Bladder tumor resection (TURBT) by PDD results in more complete resection and reduced recurrence rates. PDD-guided TURBT may have some role in reducing the risk of progression. Narrow band imaging provides increased contrast between normal and abnormal tissues based on neovascularization, thereby augmenting WLI. NBI requires a special light source. There is no need for intravesical contrast instillation. NBI is superior to WLI in the detection of bladder cancer. The addition of NBI to WLI improves the detection of flat lesions like carcinoma in situ. NBI is not useful in predicting invasive tumors or grades of tumors. NBI-directed TURBT reduces recurrence rates and recurrence free survival. But its efficacy in retarding progression is unproven. Image 1 S-enhancement utilizes software-based image enhancement modes without the need for a special light source or intravesical contrast instillation. This system provides high-quality images and identifies additional abnormal-looking areas. Another advantage of this system is simultaneous side-by-side visualization of WLI and enhanced image, providing WLI images as the control for comparison. As with PDD, S-enhancement produces a lower rate of a missed bladder cancer diagnosis. The system significantly improves the diagnosis of NMIBC. The sensitivity and negative predictive value of image 1 S enhancement increase with the increase in cancer grade. A negative test by S-enhancement effectively rules out NMIBC. All the image enhancement modalities have proven their utility in improving detection and short-term cancer control. But none of these modalities have proven their utility in delaying progression, or in long-term cancer control. Cancer progression and long-term control are governed by the biological nature of cancer cells. Early detection by optical enhancement may not be of utility in this regard. Well-designed studies are needed to establish the efficacy of these modalities in the evaluation of patients with bladder cancer. The last word, in this regard, is yet to be written.

Microbiome studies in urology- where do we stand and where can we reach?

The role of microbiome milieu in the urinary tract, their interplay in diverse urological conditions and their therapeutic implications are not completely understood. The microbiome has contributed towards urinary tract infections, urolithiasis and urological cancers. The possibility of manipulating microbiome for diagnosis and treatment is evolving. Probiotics might help in overcoming the problems of recurrent infection and antibiotic resistance. Novel applications like stents and catheters coated with non-pathogenic organisms are being developed. Research in the urinary microbiome has progressed from using mouse models to the presently available three- dimensional cultured organoids, thus making it more feasible. As our knowledge regarding the urinary microbiome increases, justice can be done to many patients in whom the advancements can be used for prophylaxis, diagnosis, treatment and even in improving their quality of life. The growing amount of antibiotic resistance is also a matter of concern and probiotics might be the answer to this upcoming calamity. In this review, we have discussed the role of the urinary microbiome in pathogenesis, diagnosis and treatment of urological conditions and pondered upon its future prospects.

Gender identity disorder (GID) in adolescents and adults with differences of sex development (DSD): A systematic review and meta-analysis.

Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment team as some of these children develop gender identity disorder (GID) when they become adults. In this systematic review and meta-analysis we have analyzed the prevalence of GID in adolescent and adults with DSD. The secondary outcome of this review is to help physicians in appropriate sex assignment of DSD children so that development of GID in later life can be reduced. METHODS: Pubmed/Index medicus were searched for "intersex" [All fields] OR "disorders of sexual differentiation AND "gender identity disorder OR gender dysphoria" [MeSH] for articles published between 2005 and 2020. Typical diagnoses included were congenital adrenal hyperplasia (CAH); complete androgen insensitivity syndrome (CAIS); partial androgen insensitivity syndrome (PAIS); 5 alpha reductase deficiency (5ARD); 17-hydroxysteroid dehydrogenase deficiency (17HSD); mixed gonadal dysgenesis (MGD) and complete gonadal dysgenesis (CGD). GID or gender dysphoria (a strong feeling of dissatisfaction about oneself as male or female) prevalence in DSD patients older than 12 years of age was extracted. Within each condition, GID percentage was compared between female and male rearing. RESULTS: The I2statistics for prevalence of GID in DSD showed high heterogeneity with I2 of 93% (95% C.I 90-95%) among the 20 articles included. The overall prevalence of GID among those with DSD was 15% (95% C.I 13-17%). CAH reared females had 4% GID while CAH reared males had significantly higher GID at 15% (p = 0.0056). All CAIS patients were raised as females and the prevalence of GID was 1.7%. GID prevalence was 12% in PAIS raised as females while 25% in those raised as males with no significant difference (p = 0.134). GID was significantly high in 5ARD (53%) and 17HSD (53%) reared as females with half of them virilizing at puberty forcing a gender change. Among sex chromosome DSD 22% of those reared as females had GID while none in those raised as male with no significant difference. CONCLUSIONS: GID is low in women with CAH, CAIS and CGD favoring female sex of rearing in these conditions. GID is high in women with 5ARD/17HSD favoring male sex of rearing in these conditions. GID is variable in PAIS or MGD and no recommendations on sex of rearing could be made in these conditions. Each DSD patient is unique and they warrant multi-disciplinary care and long term psycho sexual support.

Postnatal management of bilateral Grade 3-4 ureteropelvic junction obstruction.

INTRODUCTION: Bilateral hydronephrosis on prenatal ultrasound can be managed expectantly or with surgical intervention. The treatment strategies and outcomes are not clearly defined. METHODS: We conducted a retrospectively audit of outcomes of management of prenatally detected severe bilateral ureteropelvic junction obstruction (UPJO) in our institution.Patients with bilateral Grade 3-4 hydronephrosis were included. Those with complications like rupture, underwent bilateral intervention within 4 weeks; in the remaining, unilateral pyeloplasty was performed at 4-12 weeks. The contralateral renal unit was re-evaluated at a later date for further improvement or deterioration. All the patients were followed up with ultrasonography and renogram at 3 months, 6 months, and 1-year post operatively. The case records were analyzed for the resolution of antero-posterior diameter (APD) or the improvement in single-kidney glomerular filtration rate (s-GFR) in the operated units. RESULTS: Over 15 years, 28 patients (56 renal units) had bilateral UPJO (male-to-female ratio = 13:1). Twelve units underwent neonatal intervention to tackle the complications (6 bilateral pyeloplasty), 17 units underwent early pyeloplasty, and 15 underwent late pyeloplasty. Twelve of the twenty-two (54%) contralateral units, which were stented/observed, resolved spontaneously. Receiver operating characteristics analysis revealed that those with initial APD <25 mm and initial s-GFR >35 ml/m were more likely to improve during the observation. Ten of the forty-four operated units (22%) failed to show an improvement. Units with initial s-GFR <10 ml/m had poor chance of postoperative functional recovery. CONCLUSIONS: In neonates with bilateral UPJO, the worse affected kidney is operated first, as it still has the potential to recover. The contralateral milder UPJO unit is known to recover spontaneously following unilateral pyeloplasty. In those with bilateral Grade 4 UPJO and mass, bilateral pyeloplasty is feasible. Alternatively, unilateral pyeloplasty + contralateral cystoscopic retrograde stenting may prevent rupture or functional deterioration in the opposite kidney.

Persistent Mullerian duct syndrome: rare presentation in an elderly man.

Persistent Mullerian duct syndrome has been described as a disease of internal male pseudohermaphroditism, a rare autosomal recessive disease, characterised by persistent Mullerian derivatives in patients with male pattern 46, XY karyotype and normal pattern virilisation. We present a case of an elderly man, who on evaluation for bilateral undescended testes was found to have a pelvic mass suggestive of malignant transformation of an undescended testis on imaging. On surgical exploration, uterus with multiple fibroids, bilateral fallopian tubes, cervix and bilateral atrophic testes were identified. Interestingly, in this case, imaging (contrastCT and MRI) had missed Mullerian structures due to varied presentation, but exploration and excision of the structures followed by their histopathology revealed uterine leiomyomas and confirmed other Mullerian structures (bilateral fallopian tubes, cervix) with bilateral testes.

Utility of ultrasound elastography in postoperative follow-up of children with unilateral ureteropelvic junction obstruction.

INTRODUCTION: We aimed to determine whether shear wave velocity (SWV) on ultrasound elastography is useful in follow-up of children with ureteropelvic junction obstruction (UPJO) following pyeloplasty. METHODS: Consecutive children with unilateral UPJO who were co-operative for elastography (n = 31) were included. SWV of normal kidney was used as control, and it was compared with that of the affected kidney (UPJO) in the same patient. They were followed up with elastography at 3 months and elastography + renogram at 6 months postoperatively. In patients with a static renogram at 6 months, the study was repeated at 1 year. Patient outcomes were classified as improved at 6 months, static at 6 months, and worsened at 1 year based on ultrasound and renogram findings. The SWV was compared between the different outcomes. RESULTS: Thirty-one children with a median age of 8.5 years were studied (m:f = 29:2; L:R = 22:9). The mean SWV was significantly higher (3.21 m/s) in UPJO kidney compared to the SWV (2.72 m/s) found in normal kidney (P = 0.011). The mean SWV was significantly less at 3 months (2.73 m/s) and 6 months (2.57 m/s) postoperative follow-up (P = 0.018 and P= 0.001). Among the patients who improved, the mean SWV was 2.65 m/s. This SWV was significantly raised (3.57 m/s) in patients whose condition remained static (P = 0.006) and even higher (4.36 m/s) in those who worsened (P = 0.001). CONCLUSIONS: SWV was significantly higher in UPJO compared to normal kidneys in children. It is useful in assessing postoperative resolution, and a rising velocity can be useful as an early marker of recurrence in UPJO.

Comparative Analysis of Microleakage of Zirconia-infused Glass Ionomer Cement with Miracle Mix and Amalgam: An In Vitro Study.

Context Various restorative materials are introduced in dentistry to achieve adequate strength and restore aesthetics. Dental amalgam is a versatile material with self-sealing property, but is unaesthetic. Other restorative materials like composites require conservative preparation, but exhibit polymerisation shrinkage resulting in microleakage. To overcome these drawbacks, a high strength restorative material reinforced with ceramic and zirconia fillers known as Zirconomer (Shofu Inc., Japan) has been introduced. Aims This in vitro study aims to evaluate and compare the microleakage of zirconia-infused glass ionomer cement (Zirconomer) with Miracle Mix (GC Fuji Miracle Mix, Japan) and amalgam. Materials and methods In this in vitro study, 30 non-carious premolar teeth were randomly divided into three groups (n=10) depending on the restorative material used-Silver Amalgam (DPI, India), Miracle Mix, and Zirconomer. Standard Class V cavities were prepared on the buccal surface of 30 non-carious extracted premolars. The restored teeth were thermocycled and then immersed in 2% methylene blue dye for 24 hours. All teeth were bisected longitudinally in a buccolingual direction and observed under a stereo microscope at 40X magnification for the evidence of dye penetration. The data were analyzed using one-way analysis of variance (ANOVA) and Kruskal-Walis tests (p<0.01). Results Zirconomer showed the least microleakage in Class V cavity restoration with a statistically significant difference to amalgam and Miracle Mix. Conclusions Zirconomer has proven to be an excellent restorative material as it showed the least microleakage followed by Miracle Mix and amalgam. Zirconomer raises the bar for restorative reinforced glass ionomers by outperforming conventional glass ionomers and amalgam restoration.

Multimode smartphone biosensing: the transmission, reflection, and intensity spectral (TRI)-analyzer.

We demonstrate a smartphone-integrated handheld detection instrument capable of utilizing the internal rear-facing camera as a high-resolution spectrometer for measuring the colorimetric absorption spectrum, fluorescence emission spectrum, and resonant reflection spectrum from a microfluidic cartridge inserted into the measurement light path. Under user selection, the instrument gathers light from either the white "flash" LED of the smartphone or an integrated green laser diode to direct illumination into a liquid test sample or onto a photonic crystal biosensor. Light emerging from each type of assay is gathered via optical fiber and passed through a diffraction grating placed directly over the smartphone camera to generate spectra from the assay when an image is collected. Each sensing modality is associated with a unique configuration of a microfluidic "stick" containing a linear array of liquid chambers that are swiped through the instrument while the smartphone captures video and the software automatically selects spectra representative of each compartment. The system is demonstrated for representative assays in the field of point-of-care (POC) maternal and infant health: an ELISA assay for the fetal fibronectin protein used as an indicator for pre-term birth and a fluorescent assay for phenylalanine as an indicator for phenylketonuria. In each case, the TRI-analyzer is capable of achieving limits of detection that are comparable to those obtained for the same assay measured with a conventional laboratory microplate reader, demonstrating the flexibility of the system to serve as a platform for rapid, simple translation of existing commercially available biosensing assays to a POC setting.