Conservative treatment of Peyronie's disease: a guide.

PURPOSE: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. METHODS: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. RESULTS: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. CONCLUSIONS: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.

Urology: a trip into metaverse.

PURPOSE: Metaverse is becoming an alternative world in which technology and virtual experiences are mixed with real life, and it holds the promise of changing our way of living. Healthcare is already changing thanks to Metaverse and its numerous applications. In particular, Urology and urologic patients can benefit in many ways from Metaverse. METHODS: A non-systematic literature review identified recently published studies dealing with Metaverse. The database used for this review was PubMed, and the identified studies served as the base for a narrative analysis of the literature that explored the use of Metaverse in Urology. RESULTS: Virtual consultations can enhance access to care and reduce distance and costs, and pain management and rehabilitation can find an incredible support in virtual reality, reducing anxiety and stress and improving adherence to therapy. Metaverse has the biggest potential in urologic surgery, where it can revolutionize both surgery planning, with 3D modeling and virtual surgeries, and intraoperatively, with augmented reality and artificial intelligence. Med Schools can implement Metaverse in anatomy and surgery lectures, providing an immersive environment for learning, and residents can use this platform for learning in a safe space at their own pace. However, there are also potential challenges and ethical concerns associated with the use of the metaverse in healthcare. CONCLUSIONS: This paper provides an overview of the concept of the metaverse, its potential applications, challenges, and opportunities, and discusses the implications of its development in Urology.

Crohn's Disease-Related Stoma Complications and Their Impact on Postsurgical Course.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. The diversion through a colostomy or an ileostomy is sometimes required for disease control. In these patients, common stoma-related complications sum up with CD-related complications and often require revisional surgery. METHODS: The aim of the study was to assess stoma morbidity after surgery for CD and to identify the burden of CD-related or CD-associated complications. Thus, details of past medical history, surgery, and follow-up of 54 consecutive patients operated on for CD with any sort of stoma were retrieved from the stoma therapist prospectively maintained database. RESULTS: In our series, 23 patients had a colostomy, and 31 patients had an ileostomy. Complications occurred after stoma creation in 38 patients (70%) at a median of 1.3 months (interquartile range 0.6-7.2). CD-related complications arose in 8 patients (including pyoderma gangrenosum in 3 patients, peristomal fistulae in 2, granulomas in 2, and peristomal abscess in 1). Patients with CD-related complications tended to have a shorter disease duration (p = 0.07) and higher occurrence of CD-related complications was associated with end-stoma (p = 0.006). In this cohort, 11 cases had to be surgically treated for peristomal fistulae or abscess, parastomal hernia, prolapse, pyoderma gangrenosum, and recurrent CD. DISCUSSION/CONCLUSIONS: In patients with CD, stoma creation is burdened by a high rate of postoperative complication and a relevant rate is specifically related to CD. Often these patients are required to be reoperated on to redo the stoma. Moreover, end-stoma configuration and aggressive CD phenotype are associated to a higher rate of complications.

The impact of COVID-19 pandemic on urological emergencies: a single-center experience.

PURPOSE: COVID-19 pandemic represents a novel challenge for healthcare systems, and it affects even the daily urological practice. Italy was the first country after China to experience a lock-down period. Our objective is to determine whether, during the COVID-19 period, there has been any modification in urological emergencies. METHODS: we retrospectively reviewed urgent urological consultations requested by the Emergency Department (ED) of Padua University Hospital in the 36-day period between February 22nd and March 30th, 2020 and compared them to the prior year cases within a similar time frame (February 24th to March 31st, 2019). Pediatric population (age < 15 years); surgical complications and traumas were excluded to avoid confounding from the reduction of activities during the lockdown. The number of daily consultations, the number of invasive procedures performed and admissions were evaluated, together with the predictors of admission were identified through multivariate logistic regression models. RESULTS: The final sample resulted in 107 consultations performed in 2020 and 266 in 2019. A higher number of daily consultations was performed during 2019 (7.33 vs 2.97, p < 0.001). Similarly, the number of daily-invasive procedures was higher in 2019 (p = 0.006), while there was no difference in the number of daily admissions (15 vs 12, p = 0.80). On multivariate analysis, the year (2020 vs 2019, OR 2.714, 95% CI 1.096-6.757, p = 0.0297) was a significant predictor of admission. CONCLUSIONS: Urgent urology practice was affected during COVID-19 pandemic with a remarkable reduction in urgent urological consultations; furthermore, a higher risk of admissions was observed in 2020. The consequences of a potentially delayed diagnosis remain to be determined.

Morbidity, mortality, and quality assessment following open radical cystectomy in elderly patients with bladder cancer.

BACKGROUND: Open radical cystectomy (ORC) with pelvic lymph-node dissection (PLND) for bladder cancer (BCa) and urinary diversion is a morbid procedure, and advanced age has been associated with a higher incidence of Clavien-Dindo ≥ 3 complications. AIM: To investigate the association between chronological age, survival outcomes, incidence of perioperative complications, and quality parameters in patients undergoing ORC. METHODS: We reviewed 413 patients who underwent ORC and PLND at a single academic centre between December 2009 and June 2018 for cT2-T4N0M0 BCa. Complete clinical, demographic, and pathological data were collected in the preoperative, preoperative, and postoperative setting. Patients were categorized as ≥ 75 years or < 75 years and statistical analysis was performed accordingly. Besides descriptive statistics, Kaplan-Meier log-rank test was used. Cox regression univariate and multivariate analyses were used to assess any potential predictor of OS and CSS. RESULTS: There were 285 (69%) patients < 75 years and 128 (31%) patients ≥ 75 years old. There was no significant difference between the two age groups neither in terms of distribution of pathological stage nor in terms of overall incidence of postoperative complications. Chronological age was not significantly associated with survival outcomes on multivariate analysis. Finally, the comorbidity index was the only significant risk factor for the incidence of any complications (OR = 0.83, p = 0.002) at multivariate binary logistic regression. CONCLUSION: Open radical cystectomy (ORC) is a feasible and safe procedure in patients with high-risk non-metastatic bladder cancer. Uro-oncologists should consider evaluating elderly patients for surgery according to a thorough geriatric assessment despite chronological age.

Treatment of Penile Prosthesis Implant's Infection.

INTRODUCTION: Penile prosthesis implant is a safe and effective option in erectile dysfunction patients, being implant procedures safe with a low risk of infection. However, when infection occurs, it represents a concrete problem for both surgeon and patient. METHODS: This is a comprehensive review of all issues relating to prosthesis infection, including causes and risk factors, methods of prevention, and management. We analyzed all preoperative and perioperative factors, which can play a role in infection of the device. RESULTS: Infection of penile prosthesis implant is hard to manage and correct. While the incidence of infection following first implant is up to 3%, in cases of re-implant surgery, the rate can reach as high as 18%. Many articles were found addressing prevention and treatment of penile prosthesis infection, and many analyzed all relevant pre- and perioperative factors associated with penile prosthesis implant. Although such factors have been well studied, there is no clear consensus worldwide on certain topics. CONCLUSIONS: Penile prosthesis implant is a safe and effective option. Despite infection is a rare event, surgeons should follow strictly pre-, intra- and postoperative recommendations in order to reduce the risk of device's infection. An appropriate antibiotic therapy should be tailored on patient's characteristics and pathogens isolated.

Novel insights on testicular volume and testosterone replacement therapy in Klinefelter patients undergoing testicular sperm extraction. A retrospective clinical study.

STUDY QUESTION: To investigate whether sperm recovery is related to clinical features, hormone parameters and testosterone replacement therapy (TRT) in patients with Klinefelter syndrome (KS). SUMMARY ANSWER: This study provides three interesting insights: (i) the probability to retrieve sperm is not related to testicular volume; (ii) TRT does not affect sperm retrieval rate (SRR); and (iii) reduced levels of LH and FSH represent a negative predictor of sperm retrieval in patients with TRT. WHAT IS KNOWN ALREADY: Classical KS shows a karyotype with one extra X chromosome in all of somatic cells and clinical manifestations characterized by hypergonadotropic hypogonadism and infertility. STUDY DESIGN, SIZE AND DURATION: We performed a retrospective cohort study. Data from 111 consecutive KS azoospermic patients undergoing testicular sperm extraction (TESE) were collected from 2005 to 2016. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Data on anthropometric parameters, reproductive hormones and testicular volumes were collected. SRR was related to clinical characteristics and compared between TRT and untreated patients. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 38 patients (34.2%) had successful sperm recovery. The comparison of clinical characteristics did not differ between patients with and without sperm recovery. Sperm retrieval was successful also in subjects with smaller testes. The comparison of SRR in patients with or without TRT was not different (33.3% vs 34.6%). In TRT group, LH and FSH levels were significantly lower in subjects with no sperm retrieval (P values, respectively, <.05 and <.001). LIMITATIONS AND REASONS FOR CAUTION: Well-designed controlled studies are necessary to confirm these data aimed to set the best therapeutic approach for fertility management in hypogonadal patients with nonmosaic KS. WIDER IMPLICATIONS OF THE FINDINGS: Age at TESE, anthropometric measures, testis volume, sex hormones levels and semen parameters are not predictive parameters of SRR. Among TRT patients, reduced gonadotropin is related to failure in sperm retrieval.

Health-Related Quality of Life after Radical Cystectomy for Bladder Cancer in Elderly Patients with Ileal Orthotopic Neobladder or Ileal Conduit: Results from a Multicentre Cross-Sectional Study Using Validated Questionnaires.

OBJECTIVE: To evaluate health-related quality of life (HR-QoL) outcomes in elderly patients with different type of urinary diversion (UD), ileal conduit (IC) and ileal orthotopic neobladder (IONB), after radical cystectomy (RC) for bladder cancer, by using validated self-reported cancer-specific instruments. PATIENTS AND METHODS: We retrospectively reviewed 77 patients who received an IC or an IONB after RC. HR-QoL was assessed with specific and validated disease questionnaires, administered at last follow-up. RESULT: At univariate analysis, at a mean follow-up of 60.91 ± 5.63 months, IONB results were favourable with regard to the following HR-QoL aspects: nausea and vomiting (p = 0.045), pain (p = 0.049), appetite loss (p = 0.03), constipation (p = 0.000), financial impact (p = 0.012) and cognitive functioning (p = 0.000). This last functional aspect was significantly worse in female patients (p = 0.029). Emotional functioning was significantly better in patients without long-term complications (p = 0.016). At multivariate analysis, male gender and IONB were independent predictors of better cognitive functioning, while long-term complications negatively affected emotional functioning. CONCLUSIONS: Obtained results suggest that an IONB can also be suitable for elderly patients compared with an IC with few and selected advantages in favour of the former UD. Preoperative patient's selection, counselling, education and active participation in the decision-making process lead to a more suitable choice of treatment.

A circulating miRNA assay as a first-line test for prostate cancer screening.

BACKGROUND: Prostate cancer (PCa) screening currently relies on prostate-specific antigen (PSA) testing and digital rectal examination. However, recent large-scale studies have questioned the long-term efficacy of these tests, and biomarkers that accurately identify PCa are needed. METHODS: We analysed the levels of circulating microRNAs (miRNAs) in patients with elevated PSA who were diagnosed with either localised PCa (n=36) or benign prostatic hyperplasia (BPH, n=31) upon biopsy. Real-time RT-PCR with Taqman probes was used to measure plasma levels of miRNAs. To circumvent problems associated with circulating miRNA quantitation, we computed the expression ratios of upregulated and downregulated miRNAs. RESULTS: The miR-106a/miR-130b and miR-106a/miR-223 ratios were significantly different between the biopsy-positive and BPH groups (P<0.0001), and yielded statistical power values that were >0.99. Both miRNA ratios were highly sensitive and more specific than PSA in discriminating localised PCa from BPH. Receiver operating characteristic curve analysis revealed area under curve values of 0.81 (miR-106a/miR-130b) and 0.77 (miR-106a/miR-223). CONCLUSIONS: Testing for circulating miR-106a/miR-130b and miR-106a/miR-223 ratios may reduce the costs and morbidity of unnecessary biopsies and is feasible for large-scale screening, as it requires measuring only three miRNAs.

Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients.

OBJECTIVE: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). METHODS: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. RESULTS: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. CONCLUSIONS: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.

Postoperative Quality of Life in Patients with Ileal Neobladder at Short-, Intermediate- and Long-Term Follow-Up.

BACKGROUND: To evaluate the difference at different steps of follow-up of the postoperative quality of life (QoL) in patients who had undergone radical cystectomy and ileal orthotopic neobladder derivation. PATIENTS AND METHODS: A multicentric, cross-qualitative study was performed in 5 Italian centers of reference for the treatment of bladder cancer. One hundred seventy one patients who underwent radical cystectomy and creation of ileal orthotopic neobladder according to 'Vescica Ileale Padovana' between 2006 and 2011 have been analyzed. The validated and dedicated questionnaires EORTC QLQ-C30, IOB-PRO and EORTC QLQ-BLM30 were used. RESULTS: All data gathered were then processed, specifically means ± SD were included for comparison during 4 periods of follow-up (quartile): the first ranging from 1 to 18 months; the second ranging from 19 to 36 months; the third from 37 to 72 months and the fourth >72 months. Cancer-specific and health-related factors were analyzed separately, and the change was determined during follow-up. CONCLUSIONS: The global QoL, highlighted by validated cancer-specific and health-related questionnaires, is certainly on a satisfactory level. Thus, the education of the patient, the exploration of the pros and cons of an orthotopic neobladder and the active participation in treatment decision seem to be the keys to better improve the post-operative QoL during the follow-up period.

Behavioural profile and human adaptation of survivors after radical cystectomy and ileal conduit.

BACKGROUND: There is a lack of good data in the literature evaluating the Health-Related Quality of Life (HR- QoL) in patients with urinary diversions. The aim of this study was to examine the changes in expectation and needs in terms of human adaptation and behavioural profiles in patients with ileal conduit (IC) after radical cystectomy (RC) for bladder cancer (BC). MATERIALS AND METHODS: A qualitative, multicenter cross-sectional study using a "narrative based" approach was planned. We proceed with a sampling reasoned choice (purposive), selecting groups of patients with follow-up from one up to more than 7 years after surgery. Data were collected through individual interviews. RESULTS: Thirty patients participated in the study. The processing of the interviews allowed us to identify 2 major profiles: positive and negative. Patients with a positive profile resumed normal daily activities with no or limited restrictions both on the personal and the social level. This profile reflects a good HR-QoL. The negative profile reflects the patients for whom the ostomy has meant a worsening of HR-QoL. A positive profile was statistically more frequent in older patients (p = 0.023), with a longer follow-up (p = 0.042) and less complications rates (p = 0.0002). According to the length of follow-up and the occurrence of complitations, we identified further 5 intermediate profiles. CONCLUSIONS: Patients' satisfaction is related to the degree of adaptation to their new life with an urinary stoma and its correct management. Live "with urinary diversion" represents a new phase of life and not a deterioration.

Development of a questionnaire specifically for patients with Ileal Orthotopic Neobladder (IONB).

BACKGROUND: The ileal orthotopic neobladder (IONB) is often used in patients undergoing radical cystectomy. The IONB allows to void avoiding the disadvantages of the external urinary diversion.In IONB patients the quality of life (QoL) appears compromised by the need to urinate voluntarily. The patients need to wake up at night interrupting the sleep-wake rhythm with consequences on social and emotional life.At present the QoL in IONB patients is evaluated by generic questionnaires. These are useful when IONB patients are compared with patients with different urinary diversions but they are less effective when only IONB patients are evaluated. To address this problem a specific questionnaire-the IONB-PRO-was developed. METHODS: A) Based on a conceptual framework, narrative-based interviews were conducted on 35 IONB patients. A basic pool of 43 items was produced and organized throughout two clinical and four QoL dimensions. An additional 15 IONB patients were interviewed for face validity testing.B) Psychometric testing was conducted on 145 IONB patients. Both classic test strategy and Rasch analysis were applied. Psychometric properties of the resulting scales were comparatively tested against other QoL-validated scales. RESULTS: The IONB-PRO questionnaire includes two sections: one on the QoL and a second section on the capability of the patient to manage the IONB. For evaluation of the QoL, three versions were delivered: 1) a basic 23-item QoL version (3 domains 23-items; alpha 0.86÷ 9.69), 2) a short-form 12-item QoL scale (alpha = 0.947), and 3) a short-form 15-item Rasch QoL scale (alpha = 0.967). Correlations of the long version scales with the corresponding dimensions of the EORTC-QLQ C30 and the EORTC-BLM30 were significant. The short forms exhibited significant correlations with the global health dimension of the EORTC-QLQ and with the urinary subscales of the EORTC-BLM30. The effect size was approximately 1.00 between patients at the 1-year follow-up period and those with 3, 5, and > 5-year follow-up periods for all scales. No relevant differences were observed between the 12-item short-form and the Rasch scale. CONCLUSIONS: The IONB-PRO long and short-forms demonstrated a high level of internal consistency and reliability with an excellent discriminanting validity.

Efficacy and safety of antegrade sclerotherapy for varicocele in pediatric patients: A systematic review.

OBJECTIVES: Antegrade sclerotherapy (Tauber's) procedure has been extensively used for the minimally-invasive treatment of varicocele; however, the results in the pediatric population are less defined. This systematic review evaluates the efficacy and safety of antegrade sclerotherapy for varicocele in the pediatric population. EVIDENCE ACQUISITION: The review was conducted following the PRISMA guidelines. Systematic research of available literature in English language from 1980 until May 2022 was conducted through EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials. For each study, information was gathered regarding the study design, the inclusion/exclusion criteria, the indications for treatment, the success rate and the complications. When available, the details about sperm analysis were reported. EVIDENCE SYNTHESIS: The 10 studies were included in the final sample (564 patients). Median age of patients ranged 13.3-15.3 years. The indications for scleroembolization varied in the different studies, while most studies included patients with clinical G2-G3 varicocele and clinical symptoms or testicular asymmetry. The treatment was successful in 88%-98% of the patients, while the complication rate was <5%. CONCLUSION: Tauber's sclerotherapy is a safe and effective treatment for varicocele also in the pediatric population. Further studies with standardized inclusion criteria are needed to provide higher level of evidence and compare the outcomes of antegrade sclerotherapy with the other available techniques.

Spermatic cord sarcoma: our experience and review of the literature.

INTRODUCTION: Spermatic cord tumors represent 4% of scrotal tumors. The most common neoplasms are lipomas. Spermatic cord sarcomas (SCS) of the genitourinary tract account for 2% of all urological tumors. Herein we presented our experience in the treatment of these tumors and a review of the literature. PATIENTS AND METHODS: A review of the literature was performed using the Medline database with no restriction on language and date of published papers. The literature search used the following terms: epidemiology, surgery, chemotherapy, radiotherapy and spermatic cord sarcomas. Four cases treated from December 2009 to May 2010 are described. RESULTS: All patients were treated with radical orchiectomy. The final pathological report showed different types of sarcomas. Two of the patients were treated with adjuvant chemotherapy. 12 months after surgery, 2/4 patients were alive without signs of relapse. CONCLUSION: SCS are very rare tumors with a poor prognosis. SCS's prognostic factors have been identified in grading, size, depth of invasion and surgical margin status. Age and performance status of the patient are however very important. Lymphatic and hematogenous dissemination is uncommon. Surgery is the most important treatment both in the first approach and in local relapse. The role of adjuvant chemotherapy and radiation therapy is still debated.

Wunderlich's syndrome: three cases of acute spontaneous renal bleeding, conservatively treated.

Wunderlich's syndrome is a clinical condition defined as a spontaneous renal bleeding of non traumatic origin, contained within the Gerota's fascia. Wunderlich's syndrome is rare. Spontaneous bleeding of kidney tumors, either benign or malignant, represents the more common causes. Classically it presents with acute flank pain, tender palpable mass and clinical hemodynamic deterioration. These symptoms are defined as the Lenk's classic triad. We present three cases of spontaneous renal bleeding.

Penile calciphylaxis, infrequent complication with bad prognosis: a case report.

68-years-old man with end-stage-renal-disease (ESRD) and obesity presented with painful penile lesion: necrotic glans, extended till the penile base with the exposition of corpora cavernosa. Laboratory testing were normal and was afebrile so subsequently discharged with antibiotic therapy and medications. Clinical evaluation was suggestive for penile calciphylaxis, confirmed by seeing arterial calcifications at CT. Patient died one month later. Penile calciphylaxis is a rare life-threatening condition characterized by vascular calcification and fibrosis of medium and small arteries which causes an obstructive vasculopathy and tissue necrosis. Normalization of metabolic parameters, antibiotics, topical enzymatic debridement agents are recommended, considering the poor outcome.

Chronic Prostatitis/Chronic Pain Pelvic Syndrome and Male Infertility.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is defined as urologic pain or discomfort in the pelvic region, associated with urinary symptoms and/or sexual dysfunction, lasting for at least 3 of the previous 6 months. The rate of symptoms related to prostatitis has a mean prevalence of 8-8.2%. CP/CPPS is most frequent in men younger than 50 years, among whom it is the most common urologic diagnosis. In the last decades, many studies have been published on CP/CPPS and its association with male infertility. The pathophysiologic relation between CP/CPPS and male infertility involves several aspects, which are not well studied yet. A reduction in semen parameters has been demonstrated in patients with CP/CPPS, and several mechanisms have been proposed to represent putative pathophysiological links between CP/CPPS and infertility, including male accessory gland inflammation, metabolic syndrome, inflammatory bowel disease, HPV co-infection and autoimmunity. In light of this evidence, a multidisciplinary approach is advocated for patients with known CP/CPPS, and particular attention is needed for male patients of infertile couples in order to evaluate male accessory glands correctly. In addition, it is advisable that future studies dealing with the treatment of CP/CPPS take into consideration all the different pathophysiological aspects implicated.

Neutrophil-to-lymphocyte ratio as a prognostic factor for patients with urothelial carcinoma of the bladder following radical cystectomy.

Introduction: The pre-treatment neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse pathology or survival in a variety of malignancies, including urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Whether the prognostic value of NLR is retained, or even increased, when measured postoperatively remains to be studied. In this study, we evaluated the association of preoperative and postoperative NLR with oncological outcomes following RC. Material and methods: The NLR was recorded in 132 consecutive patients with UCB treated with open RC: before surgery (NLR1), postoperatively within 2 days (NRL2), between 7 and 15 days after RC before discharge (NLR3), and a few days before recurrence or last available follow-up (NLR4). Results: When assessed by multivariate analysis NLR1 remained independently associated with a significantly increased risk of extravesical disease (pT 3-4) (OR = 1.4, p <0.01) and lymphovascular invasion (LVI) (OR = 1.40, 95% CI 1.09-1.83, p <0.01). NLR4 was independently associated with a significantly increased risk of cancer-specific mortality (CSM) (HR = 1.14, 95%CI 1.03-1.24, p = 0.013). In a postoperative model, NLR3 was found to be an independent predictor of all-cause mortality (ACM) [HR = 1.11, 95% CI 1.02-1.21, p = 0.01]. NLR1 was associated with a significantly increased risk of recurrence in the univariable preoperative model [HR = 1.9, 95%CI 1.00-3.65, p = 0.05], while in the postoperative model NLR4 remained independently associated with a significantly increased risk of recurrence (HR = 1.13, 95%CI 1.04-1.23, p = 0.03). Conclusions: In patients with UCB treated with RC, the NLR is associated with more advanced tumour stage, LVI, lymph node metastasis, and higher CSM. Furthermore, the variation of the NLR after surgery might play a role in predicting higher ACM and recurrence-free survival.

Ranolazine-induced severe bladder hypotonia.

OBJECTIVE: To describe a case of acute urinary retention due to bladder hypotonia during ranolazine treatment. CASE SUMMARY: An 81-year-old male with multiple cardiovascular diseases was hospitalized for worsening angina and heart failure symptoms. Ranolazine 375 mg twice daily was started, in addition to ongoing therapy (clopidogrel 75 mg once daily, diltiazem 60 mg 3 times daily, isosorbide mononitrate 40 mg 3 times daily, carvedilol 6.25 mg twice daily, rosuvastatin 20 mg once daily, enoxaparin 5000 IU once daily, pentoxifylline 600 mg twice daily, pantoprazole 40 mg twice daily, enalapril 20 mg twice daily, furosemide 150 mg once daily, and spironolactone 37 mg once daily). Two months later, the ranolazine dose was increased to 500 mg twice daily; shortly thereafter, acute urinary retention occurred and persisted despite institution of α-lytic (alfuzosin) and antiandrogenic (dutasteride) therapy. A urodynamic study revealed that urinary retention was caused by severe hypocontractility of the detrusor muscle. Ranolazine was withdrawn and, within 2 days, the patient recovered his ability to void spontaneously; a second urodynamic study confirmed that detrusor contractility was substantially improved. Drug rechallenge was not performed due to the patient's clinical condition. Nevertheless, a phenotyping test to assess the activity of the cytochrome isoenzymes CYP3A4 and CYP2D6 (responsible for ranolazine metabolism) was performed, with dextromethorphan used as the probe drug. The urinary metabolic ratios indicated relatively low activity for CYP3A4 and intermediate activity for CYP2D6. DISCUSSION: The causal role of ranolazine in our case of bladder hypotonia is probable according to the Naranjo criteria. The mechanism of bladder dysfunction is tentatively ascribed to blockage of late sodium current in smooth muscle cells. Although drug plasma concentrations were not measured, they were probably elevated, since the metabolic activity of CYP3A4 was at the lower end of the reference range. Enzyme inhibition produced by diltiazem may have contributed to decreasing CYP3A4 activity. CONCLUSIONS: Acute urinary retention in elderly men taking ranolazine may be due to drug-induced bladder hypotonia.