Follow-up of non-palpable testicular incidentalomas under 1 cm: does growth rate differentiate malignant and non-malignant lesions?

OBJECTIVE: To determine whether small, incidentally detected testicular lesions can be safely followed up, by assessing growth rate and volume threshold for benign vs. malignant lesions. METHODS: This retrospective observational study includes a consecutive series of 130 testicular incidentalomas < 1 cm and with negative tumour markers identified from October 2001 to November 2022, which were initially followed up with ultrasound. A total of 39 cases proceeded to surgery during the study period, either due to lesion growth (n = 28) or patient preference/recommendation by the referring urologist (n = 11). For the lesions that were growing, specific growth rate (SGR) and doubling time (DT) were calculated assuming an exponential growth pattern. In addition, the velocity of increase of the average diameter (∆Dav) and of the maximum diameter (∆Dmax) were calculated. RESULTS: Of the 130 nodules that were initially followed up, six disappeared, eight were reduced in size, eighty-eight were stable, and twenty-eight increased in size. For operated nodules all 18 malignant tumours, 8/9 benign tumours, and 2/12 surgically proved non-neoplastic lesions were growing. The best cut-off values of the growth indicators to differentiate between malignant and non-malignant histology were 3.47 × 10-3%volume/day, ≤ 179 days, > 10 × 10-3 mm/day, and > 5 × 10-3 mm/day for SGR, DT, ∆Dmax, ∆Dav, respectively. CONCLUSIONS: Malignant and non-malignant small incidentalomas can be effectively differentiated based on growing parameters, even though overlap exists. An increase of the maximum diameter of about 1 mm and 2 mm in three months and in six months, respectively, suggests malignancy. CLINICAL RELEVANCE STATEMENT: Growing parameters allow an educated assessment of benign and malignant small testicular incidentalomas. Non-aggressive management is justified and safe when follow-up includes self-examination and tumour marker assessment to reduce the risk of interval tumour growth. KEY POINTS: Small, non-palpable and asymptomatic testicular nodules < 1 cm are unexpectedly discovered during scrotal ultrasound. Growth indicators estimate the potential malignancy, even though overlap with non-malignant lesions exists. Non-growing incidentalomas can be safely followed up.

Low-intensity laser diode plus extracorporeal shock wave therapy: a new treatment strategy in the management of Peyronie's disease.

PURPOSE: To assess the clinical effectiveness of extra corporeal shockwave therapy (ESWT) administration compared with ESWT plus a low-intensity laser diode therapy (LILDT) in the management of Peyronie's disease (PD) stable stage. METHODS: In this study, 214 patients affected by PD in stable stage (≥ 12 months), were divided into two groups. Group 1 (G1) counted 111 patients treated only with ESWT; Group 2 (G2) consisted of 103 patients that received ESWT with the same protocol of G1 plus LILDT for six weeks. The patients of both groups were assessed at baseline and follow-up for erectile function, painful erections, penile plaque size and penile curvature. The results were evaluated at baseline and 3, 6, 12 months after the treatment. RESULTS: Three months after the treatment in G2 pain in an erection or during intercourse was resolved completely in 78.6% of the patients, whereas in 55.8% cases of G1 (p < 0.003). G2 patients had a reduction of curvature degree after the 3 months treatment (p < 0.002). However, mean plaque size decreased in both groups without statistically differences with baseline values. Mean ± SD IIEF-5 score further improved significantly in the group treated with ESWT plus LILDT (p < 0.001). There were no permanent adverse sequelae after treatments. CONCLUSION: This study demonstrates an interesting therapeutic strategy when combined to the synergistic action of a shock wave therapy with low-intensity laser therapy on the stable plaques with significant benefits in terms of pain perception, penile curvature and sexual activity.

Detection of disease-causing mutations in prostate cancer by NGS sequencing.

Gene mutations may affect the fate of many tumors including prostate cancer (PCa); therefore, the research of specific mutations associated with tumor outcomes might help the urologist to identify the best therapy for PCa patients such as surgical resection, adjuvant therapy or active surveillance. Genomic DNA (gDNA) was extracted from 48 paraffin-embedded PCa samples and normal paired tissues. Next, gDNA was amplified and analyzed by next-generation sequencing (NGS) using a specific gene panel for PCa. Raw data were refined to exclude false-positive mutations; thus, variants with coverage and frequency lower than 100× and 5%, respectively were removed. Mutation significance was processed by Genomic Evolutionary Rate Profiling, ClinVar, and Varsome tools. Most of 3000 mutations (80%) were single nucleotide variants and the remaining 20% indels. After raw data elaboration, 312 variants were selected. Most mutated genes were KMT2D (26.45%), FOXA1 (16.13%), ATM (15.81%), ZFHX3 (9.35%), TP53 (8.06%), and APC (5.48%). Hot spot mutations in FOXA1, ATM, ZFHX3, SPOP, and MED12 were also found. Truncating mutations of ATM, lesions lying in hot spot regions of SPOP and FOXA1 as well as mutations of TP53 correlated with poor prognosis. Importantly, we have also found some germline mutations associated with hereditary cancer-predisposing syndrome. gDNA sequencing of 48 cancer tissues by NGS allowed to detect new tumor variants as well as confirmed lesions in genes linked to prostate cancer. Overall, somatic and germline mutations linked to good/poor prognosis could represent new prognostic tools to improve the management of PCa patients.

Differences in surgical and functional outcomes in benign prostate hyperplasia patients with only lower urinary tract symptoms versus those in retention: A systematic review and meta-analysis.

AIMS: To evaluate outcomes after benign prostate hyperplasia (BPH) surgery among men with lower urinary tract symptoms (LUTS) only versus those with urinary retention (UR). METHODS: The protocol was registered in PROSPERO with ID#232253. Eligible studies identified from four electronic databases. Search, data extraction and quality assessment were performed independently by two reviewers. Studies with perioperative, functional, early and late complication outcomes included. RESULTS: Twenty-five studies, 14 593 patients including 1 randomized controlled trial, 11 prospective and 13 retrospective studies included for meta-analysis. This showed higher risk of immediate transient recatherization (risk ratio [RR]: 5.29, p < 0.00001), longer days to trial-off-catheter (mean difference [MD]: 0.25, p < 0.00001), longer hospitalization stay in the UR group (MD: 0.35, p < 0.00001), and higher risk of intraoperative blood transfusions (RR: 1.90, p = 0.002), postoperative urinary tract infections (RR: 1.49, p < 0.00001) and sepsis (RR: 8.15, p = 0.009) too. Failure of surgery like permanent recatheterization (RR: 5.27, p < 0.00001) was more in preoperative UR group. Negligible differences seen in long term functional outcomes between the two groups (International Prostate Symptom Score at 12 months, MD: -0.06, p = 0.68; Quality of Life at 12 months, MD: 0.20, p < 0.00001; maximum urinary flow rate at 12 months, MD: -0.33, p = 0.10; and postvoid residual volume at 12 months, MD: 4.32, p < 0.00001). CONCLUSIONS: Preoperative UR patients undergoing surgery for BPH have higher risk of postoperative complications versus LUTS only group including the need for permanent catheterization. Both groups had similar long-term functional outcomes. We could infer that patients with UR on whom surgery is successful, with time may recover bladder function akin to patients with LUTS alone.

The induction of AMPK-dependent autophagy leads to P53 degradation and affects cell growth and migration in kidney cancer cells.

The most common subtype of renal cell carcinoma (RCC) is the clear cell RCC (ccRCC) that accounts for 70-80% of cases. The fate of ccRCC is linked to alterations of genes that regulate TP53. The dysfunction of p53 affects several processes including autophagy, which is increased in different advanced carcinomas and could be associated with cancer progression. We report that different kidney cancer cell lines show higher levels of autophagy than control cells. The increased autophagy is associated with the upregulation of miR501-5p, which stimulates mTOR-independent autophagy by the activation of AMP kinase. AMPK activation occurs through the decrease of ATP generation caused by the downregulation of the mitochondrial calcium uniporter (MCU) that leads to the reduction of mitochondrial calcium uptake. Autophagy induction promotes the degradation of p53 through the autophagolysosomal machinery. Consistently, the inhibition of autophagy reduces both cell proliferation and migration enhancing the expression of p53, p21 and E-Cadherin as well as decreasing Vimentin synthesis. Taken together, these findings indicate that autophagy is involved in the progression of kidney cancer. Therefore, the pharmacological targeting of this process could be considered an interesting option for the treatment of advanced renal carcinoma.

MicroRNA501-5p induces p53 proteasome degradation through the activation of the mTOR/MDM2 pathway in ADPKD cells.

Cell proliferation and apoptosis are typical hallmarks of autosomal dominant polycystic kidney disease (ADPKD) and cause the development of kidney cysts that lead to end-stage renal disease (ESRD). Many factors, impaired by polycystin complex loss of function, may promote these biological processes, including cAMP, mTOR, and EGFR signaling pathways. In addition, microRNAs (miRs) may also regulate the ADPKD related signaling network and their dysregulation contributes to disease progression. However, the role of miRs in ADPKD pathogenesis has not been fully understood, but also the function of p53 is quite obscure, especially its regulatory contribution on cell proliferation and apoptosis. Here, we describe for the first time that miR501-5p, upregulated in ADPKD cells and tissues, induces the activation of mTOR kinase by PTEN and TSC1 gene repression. The increased activity of mTOR kinase enhances the expression of E3 ubiquitin ligase MDM2 that in turn promotes p53 ubiquitination, leading to its degradation by proteasome machinery in a network involving p70S6K. Moreover, the overexpression of miR501-5p stimulates cell proliferation in kidney cells by the inhibition of p53 function in a mechanism driven by mTOR signaling. In fact, the downregulation of this miR as well as the pharmacological treatment with proteasome and mTOR inhibitors in ADPKD cells reduces cell growth by the activation of apoptosis. Consequently, the stimulation of cell death in ADPKD cells may occur through the inhibition of mTOR/MDM2 signaling and the restoring of p53 function. The data presented here confirm that the impaired mTOR signaling plays an important role in ADPKD.

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia.

PURPOSE: We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. MATERIALS AND METHODS: We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. RESULTS: Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (pv0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. CONCLUSIONS: This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Sonographic patterns of Peyronie's disease in patients with absence of palpable plaques.

PURPOSE: Non-palpable isolated septal plaques of the penis are likely present in a significant number of patients affected by erectile dysfunction (ED) and penile pain without deformity or curvature. The aim of this study was to evaluate the ultrasound (US) patterns observed in patients investigated for ED or penile pain without curvature. MATERIALS AND METHODS: We reviewed the medical records of 386 patients who underwent an initial colour-Doppler ultrasonography (CDU) of the penis for DE and/or penile pain without curvature. After satisfying inclusion criteria, 41 patients were individualized. All patients had a non-palpable plaque with involvement of the penile septum. Three US patterns were identified: focal hyperecoic thickening of the intercavernosum septum (IS) with acoustic shadow (pattern 1), non-calcified thickening (isoechoic or slightly hyperechoic (pattern 2), and microcalcifications in the IS without associated acoustic shadow (pattern 3). RESULTS: Patients' mean age was 51.3±16.7. ED was the predominant disorder in 73.2% of patients, followed by penile pain and length loss in 19.5% and 7.3% of patients, respectively. 32(78.1%) patients showed the pattern 1, 6 (14.6%) pattern 2, and 3 (7.3%) pattern 3. Plaques size varied from 3 to 13 mm. The penile hemodynamic response to CDU reported abnormal findings distally to the septal plaques in 20 patients (<25cm/sec). Median left and right cavernosum artery flows measured a peak systolic velocity of 31cm/sec and 33 cm/sec, respectively. CONCLUSIONS: We believe that an US study with CDU provides a way to characterize, localize, and deliver treatment choice in patients with Peyronie's Disease.

Rupture of the cavernous body diagnosed by contrast-enhanced ultrasound: Presentation of a clinical case.

Penile trauma represents a urological emergency characterized by the breaking of the albuginea tunic. A fast diagnosis and early surgical repair are the best treatments to avoid post-operative sequelae such as curvatures or deformities of the penis. An ultrasound evaluation may not be able to identify the injury in the tunica albuginea due to the edematous swelling of the penis and clots within the tear deteriorate the image contrast and can hide the injury. We here report a case study of successful management via surgical treatment for rupture of the cavernous body diagnosed by contrast-enhanced ultrasound in a young patient with penile trauma.

Are ultrasonographic measurements a reliable parameter to choose non-palpable testicular masses amenable to treatment with sparing surgery?

PURPOSE: To analyze the dimensional characteristics between non-palpable testicular masses detected during ultrasonographic (US) study and their postoperative dimensions reported in definitive histological diagnosis, and evaluate if the sonographic measurements may be a relevant parameter to improve the identification of testicular lesions amenable to treatment with testicular-sparing surgery (TSS). METHODS: A total of 77 patients who underwent radical orchiectomy or TSS for non-palpable testicular masses suspected for malignant neoplasms were included into this study. Preoperative US studies were also carried out in all patients to evaluate the diameter, volume and sonographic characteristics of the testicular lesions and the contralateral testes. All patients underwent inguinal orchiectomy or testicular exploration (for masses ≤1.5 cm) through an inguinal approach. RESULTS: The mean age at the time of diagnosis was 36.5 years. The predominant finding was a hypoechoic mass (71.4%). The vast majority of all malignant masses appeared markedly hypoechoic (89.8%); moreover, this differed significantly from benign lesions (39.3%, p<0.001). Calcified lesions were significantly associated with benign tumors (77.8%, p<0.002). The mean maximum lesion diameter of the affected testicle determined by preoperative US study was 14.1 mm (range 7-21). The mean maximum lesion determined postoperatively by pathology was 13.4 mm (range 5-20). Tumor lesions estimated by US study were more accurate in benign tumors, but the results were not statistically significant (p=0.323). CONCLUSIONS: We demonstrated that the sonographic diameter of the testicular lesions seems to be one of the most important parameter for the indication of an elective TSS and US is an accurate method for detecting and measuring these lesions.

Ultrasound detection of prostatic calculi as a parameter to predict the appearance of hematospermia after a prostate biopsy.

PURPOSE: We evaluated the correlation between prostate calculi and hematospermia in patients undergoing prostate biopsy, and its impact on sexual activity of patients. MATERIALS AND METHODS: A single-center prospective randomized study of 212 patients referred for transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed. All patients were divided into two groups: Group A (GA), 106 patients with moderate/marked presence of prostatic calculi visualized by TRUS; Group B (GB), 106 patients with absence/scarce of prostatic calcifications. Patients were handed questionnaires to obtain a validated data on the duration and impact of hematospermia on sexual activity. The anxiety scores were recorded using a visual analogue scale. RESULTS: No significant difference was noted between the two groups when comparing age, preoperative PSA level, prostate volume, and biopsy number, except for digital rectal examination (DRE) findings. Post-biopsy results of patients included in GA revealed that the complication of hematospermia was present in 65.1%, while in GB was present in 39.7% (p<0.001). On multivariate analysis for identifying significant preoperative predictors of hematospermia, which included variables of age, PSA, prostate volume, and prostate cancer were not shown to be significant predictors of hematospermia, except DRE and prostate calculi (p<0.001). The mean anxiety score was 3.7±2.8 in GA and 2.3±1.9 in GB, respectively (p<0.001). CONCLUSIONS: Prostatic calculi are an independent predictive factor of severe hematospermia after TRUSBx on the basis of multivariate analysis, but don't affect the positive rate of prostate cancer. Patients should be adequately counselled before TRUSBx to avoid undue anxiety and alterations in sexual activity.

Tadalafil once daily: Narrative review of a treatment option for female sexual dysfunctions (FSD) in midlife and older women.

Female Sexual Disorders (FSD) include a complex, multidimensional, individual experience that can change as an individual age, suggesting that these problems are caused by multiple factors including psychosocial factors, personal relationships, pathologic changes caused by diseases, and pharmacologic influences. Menopause is an important time for middle aged women and postmenopausal physiological changes could have a significant role in the development of FSD. Few is still known about their correct definition and treatment. Their incidence, prevalence and risk factors are difficult to define because of a high level of overlap in the experience of problems with desire, arousal, and orgasm. Little evidences are known about the best therapeutic approach, and both non-pharmacological and pharmacological treatment options have been described. Among these, phosphodiesterase type 5 inhibitors could be an effective option for many subtypes of female sexual disorders, with an improvement in different aspects of sexual function, such as desire, arousal, orgasm and sexual satisfaction. In this paper authors reviewed what is already known about the use of these vasoactive agents, particularly tadalafil, as a treatment option for female sexual disturbances.

Ultrasound findings of ruptured Peyronie's plaque: Case report and review of the literature.

We present here a rare case of rupture of tunica albuginea and corpus cavernosum, in the site of a Peyronie's plaque, which happened in a 61- year-old man during a vacuum cleaner masturbation. Ultrasound study showed an irregular hyperechoic defect at the cavernosal rupture site in correspondence of the Peyronie's plaque. The hematoma was evacuated, partially plaque excised, and the tear repaired. Ultrasonography is an ideal technique for evaluating patients with penile trauma and can be routinely used in an emergency. It is a non-invasive method that gives faster results than cavernosography and Magnetic Resonance Imaging.

Right ectopic intrathoracic kidney: Unusual clinical presentation in a young patient affected by scrotal varicocele.

Intrathoracic kidney is a partial or complete displacement of the kidney above the hemidiaphragm into the mediastinal compartment of the thorax. It is usually seen as an incidental finding discovered on chest radiograph or abdominal ultrasound. However computed tomography consents the correct detection of intrathoracic masses and defines their shape, size, and extent. We here report a case of ectopic thoracic kidney in a 22-year-old man who had a long history of scrotal discomfort associated with right varicocele. Frequently, this ectopia does not affect renal function and the stretched ureter provides good drainage. In literature, a small number of cases shows that varicocele is a possible mode of presentation of kidney tumors, but this is the first case of varicocele secondary to intrathoracic kidney ectopia.

Safety of transrectal ultrasound-guided prostate biopsy in patients affected by Crohn's disease.

PURPOSE: Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. It is usually considered a contraindication to transrectal ultrasound-guided prostate biopsy (TRUSBx). The aim of this study was to investigate the safety of TRUSBx in a small cohort of patients with CD. METHODS: We queried our institutional database clinical data of patients with a diagnosis of CD undergoing TRUSBx, and a retrospective prospective study of 5 patients was planned. All patients enrolled were in the remission phase of CD and asymptomatic. They received the same antibiotic prophylaxis and a povidone-iodine aqueous solution enema before the procedure. A standardized reproducible technique was used with using a ultrasound machine equipped with a 5-9 MHz multifrequency convex probe "end-fire". The patients were treated under local anaesthesia, and a 14-core biopsy scheme was performed in each patient as first intention. After the procedure each patient was given a verbal numeric pain scale to evaluate tolerability of TRUSBx. RESULTS: TRUSBx was successfully completed in all patients. The number of biopsy cores was 14 (12-16). Of the 5 biopsy procedures performed 40% revealed prostatic carcinoma (PCa) with a Gleason score 6 (3+3). No patients required catheterization or admission to the hospital for adverse events after the procedure. The most frequent adverse event was hematospermia (60%), while hematuria was present in 20% of patients and a minimal rectal bleeding in 20% of the patients. No patients reported severe or unbearable pain (score ≥ 8). CONCLUSIONS: This study suggests that CD may not be an absolute contraindication to TRUSBx for prostate cancer detection, but still requires a careful patients selection.

Distant subcutaneous spreading of Fournier's gangrene: An unusual clinical identification by preoperative ultrasound study.

We present here the first case of successful management via preoperative ultrasonographic (US) study to detect a distant spreading of Fournier's gangrene (FG), which was happened in a 75-year-old man. US study showed the necrotizing infection in the periumbilical region distant 22 cm from the genital tract. A target incision of this periumbilical area and debridement of necrotic tissues was made. Computed tomography (CT) is superior to ultrasonography to confirm the diagnosis of FG and support in surgical management, but a CT evaluation in patients with FG may be limited by the frequent presence of concurrent acute renal failure or patient hemodynamic instability. Ultrasonography is an ideal technique for evaluating patients in bedside settings and can be routinely used in an emergency.

Pelvic congestion syndrome: the current state of the literature.

PURPOSE: Pelvic congestion syndrome is an uncommon poorly understood and frequently misdiagnosed disorder of the pelvic venous circulation, which causes chronic pelvic pain in women in premenopausal age. This condition has typical features, such as pelvic varicosities, pelvic pain worsened by prolonged standing, coitus, menstruation, and pregnancy. METHODS: The precise etiology of this syndrome remains uncertain, and it is probably multifactorial. Valvular insufficiency, venous obstruction, and hormones all may play a role in the development of congestion of the pelvic veins. RESULTS: Pelvic pain and venous varices are often both present in premenopausal women, but not necessarily causally related. Furthermore, incompetent and dilated pelvic veins are a common finding in asymptomatic women. As such, it is challenging but important to determine which patients have chronic pelvic pain specifically related to pelvic congestion syndrome in order to treat them properly. CONCLUSIONS: Once the syndrome has been accurately diagnosed, medical, surgical, or minimally invasive endovascular treatments can improve symptoms in a high percentage of cases. This updated nonsystematic review of the literature explores the pathophysiology, clinical features, diagnostic investigations, and treatment option of this complex condition that affects young women with considerable implications for their daily social and psychological condition.

Reply to the letter: We really need a classification of prostatic abscess?

Not available.

Ultrasonographic study of subcutaneous penile granuloma secondary to silicone injection.

Penile augmentation has been reported in the literature by injecting various materials. This study reports our experience in management of penile augmentation complications associated with selfpenile injection of silicone liquid. After a careful ultrasound study, the penile skin was excised through a circumferential sub-coronal incision and dissected with the silicon mass. Histology was well-compatible with silicone granulomas. The patient was discharged after 24 hours. Ultrasonography has permitted preoperatively to determine if the plane between the indurated inflammatory tissue and the Buck's fascia was preserved for the complete surgical excision of affected tissue.

Ultrasound evaluation of the striated urethral sphincter as a predictive parameter of urinary continence after radical prostatectomy.

OBJECTIVES: The purpose of this study was to evaluate preoperatively the results of transrectal ultrasound (TRUS) in the detection of morphological, vascularization status of urethral rhabdosphincter (RS) and evaluate the correlation with urinary continence after radical prostatectomy (RP). METHODS: 211 patients who underwent RP were prospectively studied using TRUS scan of the RS thickness. At the end of the examination a study was performed with the use of colour-Doppler for the assessment of the RS vascularity pattern. The level of continence was graded on a 5 point scale as: 1 = complete continence, 2 = 1 pad daily, 3 = 2-3 pads daily, 4 = 4 or more pads daily, and 5 = complete incontinence. RESULTS: It was possible to visualize the rhabdosphincter and its vascularity in all patients. Patients with normal continence (level 1 and 2) showed a sphincter-muscle thickness of 3.5 mm (± 0.4) and a hypoechoic ultrasound pattern. With respect to the other levels 3, 4 and 5 of urinary incontinence RS thickness was 2.8 mm (± 0.5), 2.1 mm (± 0.6), 1.7 (± 0.7) respectively. Incontinence after RP (≥ 3 level) was associated with urethral sphincter deficiency in the great majority of patients. Statistical significant differences were observed in the vascularity between continent and incontinent men in all measured vascularity variables (p < 0.005). CONCLUSIONS: This study suggests that RS integrity is a good predictor of urinary continence after RP and this information can be important during the preoperative phase as part of the informed consent.