Uro, Volume 1, Issue 3 (September 2021) – 13 articles

Interstitial Cystitis and Painful Bladder Syndrome are chronic conditions that are associated with urinary frequency, urgency, pain, and nocturia. The etiology of IC/PBS is not clearly understood, therefore diagnosis and treatment can be challenging. IC/PBS greatly affects the quality of life in several ways. In this report, we present the case of a patient with longstanding interstitial cystitis symptoms who was successfully treated with a novel approach after failing treatment established by the current guidelines in the management of IC/PBS. This case illustrates the complex nature of this syndrome and offers a new treatment approach that can potentially change the way IC/PBS are medically managed. Full article

Background: Peyronie’s disease (PD) is a little-known disease characterized by pain during erections, the presence of penile curvature, and consequent psychological disorders. In addition, concomitant erectile dysfunction may be present. The treatment of PD is adapted to the patient, especially when the penile curvature is >60°; with stabilized pathology, it is preferable to perform penile straightening approaches, such as penile plication and plaque incision, or partial excision and grafting. The most frequent side effect of straightening approaches is the onset of erectile dysfunction due to the formation of venous leakage appearing after the excision of calcific plaque. Materials and methods: All enrolled patients had PD, a curvature >60°, had an IIEF subdomain erectile function score >16, and refused penile prosthesis implantation concurrent with tunica albuginea grafting surgery. Subsequently, 4 weeks after surgery, all patients underwent a rehabilitation protocol that consisted of low-intensity extracorporeal shock wave therapy (Li-ESWT), the administration of 5 mg/daily of tadalafil, and the use of a vacuum device. Results: From January 2014 to March 2016, 15 subjects affected by PD with severe penile curvatures were enrolled in the study. At 6 months after surgery, the IIEF scores for erectile function were not statistically significantly different before and after surgery (p > 0.05); the other items, especially orgasmic function (p = 0.01), sexual desire (p < 0.01), intercourse satisfaction (p = 0.01), and overall satisfaction (p = 0.04), were all statistically significant. The modified EDITS questionnaire reported that 80% of patients were satisfied, that 13.3% were dissatisfied, and that 1 patient (6.6%) was dissatisfied with the surgery. Moreover, there was no statistically significant decrease in the patients’ penile lengths. The aim of this study was to use a rehabilitation protocol consisting of Li-ESWT, the administration of 5 mg/daily, and the use of a vacuum device in order to preserve the erectile function of patients undergoing straightening approaches using surgical grafting. In addition, patient satisfaction following surgery was analyzed. Full article

Calcineurin inhibitors (CNIs) are typically used to prevent organ rejection and their use has significantly improved allograft and survival rates with a marked reduction in rejection rates. However, CNIs have been associated with various side effects including nephrotoxicity, hypertension, gingival hyperplasia, hypertrichosis, hepatotoxicity, hyperkalemia, and neurotoxicity. Significant intra-patient and interpatient pharmacokinetic variability and narrow therapeutic indices make the therapy complicated. Although CNIs are essential in preventing organ rejection, higher doses could lead to toxicity, which can reduce patient tolerability and negatively affect long-term allograft survival and patient mortality. As individual patients respond differently to comparable drug levels, attaining the optimal drug level range does not ensure lack of drug toxicity or complete immunosuppressant viability. One to two adverse effects are commonly observed in patients using CNIs. However, no case about CNI-induced gingival hyperplasia, hypertrichosis, tremors, facial nerve palsy, and blepharospasm after kidney transplantation in a single patient has been reported. Our report describes the unusual case of a patient presenting with CNI-induced multiple adverse reactions. Full article

Parts I and II of this three-part series indicated how a global review of both English-language and non-English language papers, plus a focus on a lipidosterolic extract of Serenoa repens (LSESr) having a standardized fatty acid profile, have together engendered new insights about the biological activity of LSESr vs. LUTS. In this last part, data from the world literature is presented that confirms that LSESr efficacy is the predominant finding in clinical trials. Despite two placebo-controlled clinical trials performed in the U.S. that failed to confirm a benefit of LSESr vs. placebo in LUTS, the global body of the peer-reviewed literature attests not only to efficacy but also to safety. Results will be presented of important trials that compare LSESr to alpha-blockers such as tamsulosin (Flomax^®) as well as to 5α-reductase inhibitors such as finasteride (Proscar^®) that demonstrate consistent findings of near equivalency between LSESr and these pharmacologic agents. Studies relating data indicative of an additive effect or synergy between LSESr and tamsulosin will also be presented. The heightened effectiveness of LSESr in men with severe LUTS vs. moderate LUTS expands the importance of our scrutiny of the global literature concerning LSESr. Of great consequence are the contributions of non-English language peer-reviewed publications that have consistently provided evidence of LSESr efficacy in treating LUTS/BPH. These peer-reviewed articles have shown that the effect of LSESr is not that of a placebo. Finally, a comparison of the LSESr extraction products used in the treatment of LUTS, and a discussion of the milieu factors that affect the natural history of LUTS and influence the outcome of clinical trials, complete this detailed analysis of LSESr vs. LUTS. Full article

Part I of this 3-part series provided the groundwork for understanding the role of a standardized lipidosterolic extract of Serenoa repens (LSESr) in the treatment of LUTS. It documented that a treatment having a high therapeutic index (i.e., a ratio of benefit to adverse reactions) is a critical need in the demographic context of a rapidly growing elder population. Part I described the clinical symptomatology of LUTS and how it is quantified. A critique of the reports from four authoritative bodies: the European Scientific Cooperative on Phytotherapy (ESCOP), Cochrane 2012, the European Medicines Agency (EMA), and the AUA (American Urological Association) was presented. The foundation above then fine-tuned our search to require (a) consistent evaluability criteria, (b) the quantification of clinical findings, (c) the need to focus on studies employing a standardized LSESr product meeting the fatty acid profile set forth by the European Medicines Agency (EMA) and the US Pharmacopeia and (d) a global assessment of scientific investigations published in all languages and not limited to only English. With the above four constraints, “new” findings about LSESr vs. LUTS are presented. How did the search strategy and selection criteria lead to new understandings about the role of LSESr vs. LUTS? How safe is LSESr in contrast to its counterpart prescription drugs? Of the proposed major mechanisms of action of LSESr (e.g., 5-alpha reductase inhibition and anti-inflammatory activity), what are the key points? After initiating treatment with LSESr, when is clinical improvement seen? How durable is LSESr in ameliorating LUTS? Can LSESr prevent the progression of BPH? Full article

Lower urinary tract symptoms (LUTS) are classically characterized as being related to storage (e.g., frequency, urgency, and nocturia) or flow (e.g., weak stream, intermittency, straining, and incomplete emptying). Conventional prescription medications such as α1-blockers and 5α-reductase inhibitors are used to treat progressive LUTS in men. Due to the adverse events associated with these prescription drugs, many patients with mild-to-moderate LUTS may decide to initiate treatment with non-prescription medications and/or dietary supplements. The lipidosterolic extract of Serenoa repens (LSESr), at a recommended daily dose of 320 mg/day, has been the focus of numerous peer-reviewed studies and review articles concerning the treatment of LUTS, from the first publication in 1983 by Boccafoschi to the most recent publication in 2021 by Russo. Although it seems improbable that the beneficial effect of LSESr reflects a placebo effect given the consistent degree of efficacy comparing various studies published in different countries over a span of almost 40 years, this has been the prevailing impression stemming from essentially three publications in the Western medical literature. In addition, despite publications reporting findings of almost identical efficacy using LUTS endpoints such as the International Prostate Symptom Score (IPSS), the quality of life score (QoL), and the peak urinary flow (Qmax) in comparing LSESr with the α-blocker tamsulosin or the 5α-reductase inhibitor finasteride, and despite the recognized acceptance of the hexane lipidosterolic extract product (Permixon^®) as an herbal medicine in Europe showing value in the treatment of LUTS, the use of LSESr remains controversial in the US. Contributing to such an opposing view in the US are the wide variability in quality, composition, and dosage of Serenoa products, the commercial prevalence of dried berry powder supplements, and the lack of awareness of a standardized Serenoa phytotherapy lipidosterolic profile. Can the controversy over the efficacy of LSESr in the context of LUTS be resolved? By understanding the main literature that has led to clinical practice guidelines for Serenoa repens for LUTS in Europe and the US, and by an in-depth analysis of the totality of the clinical literature concerning dose, extraction method, and quality of the Serenoa product used, it should be possible to answer this question. Given the extent of this global analysis, this report is presented in three sections. Part I introduces LUTS. What are the demographics of LUTS? What symptoms are assessed by LUTS, and how do we quantify LUTS? Why would a non-prescription item be a valuable consideration in LUTS treatment versus other treatment options? What is basic information about Serenoa repens, and what defines a standardized LSESr product? What are the published trials that have affected the acceptability of Serenoa repens in the treatment of LUTS? Finally, a major portion of Part I discusses the four major reviews of Serenoa repens versus LUTS that have influenced how it is accepted in the USA, in Europe, and in other parts of the world. Part I, therefore, lays the groundwork and is foundational for the important findings relating to LUTS and Serenoa repens that will be presented as Parts II and III in subsequent review articles. Full article

Objectives: To examine the most recent literature and published science in determining any and all possible associations between pediatric obesity and pediatric urolithiasis. Methods: Retrospective literature review of pediatric stone formers with diagnosed stone disease and all associated risk factors. Peer-reviewed, published manuscripts from the past several decades were analyzed for risk factors associated with pediatric obesity such as diet, hypertension, and renal diseases. Comparing the pediatric obesity literature with the pediatric stone forming literature, any associations and correlations were derived and analyzed. Results: Despite the existing evidence that obesity is linked to stones in adults, the evidence remains unclear whether obesity plays a role in children. Nutritional discrepancies, in the setting of the obesity epidemic, have been shown to alter the risk profile of pediatric patients. Consistent with the published literature, and lack of consistent correlation with obesity and stone disease, is the knowledge that age, gender, geography, and climate may all play a role in the onset of pediatric obesity and may also be on the causal pathway toward pediatric urolithiasis. Conclusion: The manuscript demonstrates that there are a number of risk factors, congenital or acquired, that are associated with pediatric obesity. The mechanisms responsible for these associations may be on the causal pathway toward childhood urolithiasis. These mechanisms that underlie these associations need to be further investigated. Full article

Background: The sexual health of young people is an especially important issue for national health policies. Adolescents, in fact, are at elevated risk for adverse sexual and reproductive health outcomes relative to their habits, sexually transmitted infections (STIs), sexual behaviour and teenage pregnancy. The aim of this study was to assess the knowledge about sexuality of students under the age of 18. Moreover, we aimed to explore the influence of sex education on sexual knowledge and behaviour. Methods: The participants were enrolled during a cultural exchange project in September 2019. After completing the questionnaire, all students took part in a sex education course performed by an urologist with expertise in sociology and psychology. The adolescents repeated the same survey in a web form in September 2020, one year after the course. Results: Analyzing the data, sex education lessons helped to improve students’ confidence in approaching all the issues of the questionnaire. Moreover, we observed a significant increase in the role of school as main source of information, while the role of the internet, media and family remained stable. Conclusions: This study encouraged the introduction of school-based sexual education policies, pointing to opportunities for structural early intervention programs. Full article

This is a critical review of the current literature data about sexual dysfunction as a potential side effect related to drugs commonly used for the treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms. In this narrative review, we analyzed data from the literature related to the development of sexual dysfunctions during the treatment of BPH or LUTS. Both α-blockers and 5-alpha reductase inhibitors (5-ARIs) can induce erectile dysfunction, ejaculatory disorders and a reduction in sexual desire. The sexual side effect profile of these drugs is different. Among the α-blockers, silodosin appears to have the highest incidence of ejaculatory disorders. Persistent sexual side effects after the discontinuation of finasteride have been recently reported; however, further studies are needed to clarify the true incidence and the significance of this finding. However, most of the published studies are affected by a weak methodology and other important limitations, with only a few RCTs available. Therefore, it is desirable that future studies will include validated tools to assess and diagnose the sexual dysfunction induced by these medications, especially for ejaculation and sexual desire disorders. Full article

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy characterized by renal loss of calcium and magnesium leading to progressive renal failure. The disorder is caused by variants to the tight junction proteins claudin-16 and -19. While rare, this disorder causes a significant burden to patients based on its clinical manifestations of various electrolyte abnormalities, nephrocalcinosis, and early progression to renal failure. In this report we describe the diagnosis of a novel variant of CLDN16 which clinically presented with severe hypomagnesemia, hypocalcemia, nephrocalcinosis, and renal failure. Full article

(1) Background: Pelvic organ prolapse (POP) is common among post-menopausal women affecting more than 25% in their lifetime—with 11% having a lifetime risk of undergoing an operation for a POP. In April 2019, the Food and Drug Administration (FDA) took surgical mesh for transvaginal use off the market due to safety and effectiveness concerns. This leaves colporrhaphy or colporrhaphy with bio-graft options for a POP surgical repair. (2) Case: In this report, we look at a case with anterior mesh erosion complicated by poor wound healing secondary to heavy tobacco use and how it was successfully removed and augmented with a Coloplast axis allograft dermis biological graft secured with an Anchorsure sacrospinous ligament/arcus tendineus fascia pelvis fixation device and prolene suture. (3) Results: After failing two prior surgeries to rectify the mesh erosion, a final procedure was performed using a biologic dermal graft and a double-layer closure to aid in protecting and increasing the integrity of the tissue. (4) Conclusions: Collectively, the patient and her surgeries highlight the difficult nature of complete mesh removal and how tobacco use can significantly affect the proper healing of surgical sites. The number of surgeries necessary to address the patient’s chief complaint and the resolution of her symptoms with the biologic graft supports the challenges one faces with mesh removal and poor wound healing secondary to tobacco use. This case illustrates that complicated transvaginal mesh erosion should initially be augmented with a biologic dermal graft secured via sacrospinous ligament/arcus tendineus fascia pelvis fixation and double-layer closure and not only if visible mesh removal alone fails. Full article

(1) Introduction and Objective: Upper tract urothelial carcinoma (UTUC) is an uncommon disease, only accounting for 5–10% of all urothelial carcinomas. Current clinical practice guidelines encourage a risk-adapted approach to UTUC management, including lymph node dissection (LND) in patients with muscle-invasive or high-risk tumors. If pathological characteristics could be more accurately predicted from preoperative data, we could optimize perioperative management strategies and outcomes. The aim of this article is to present a detailed revision of preoperative predictors for muscle-invasive UTUC, locally advanced or advanced UTUC, as well as current indications, technique variations, and the reasons as to why LND should be offered to these patients. (2) Methods: We included any kind of studies related to information concerning UTUC, nephroureterectomy, LND, risk factors for recurrence, prediction tools and models for risk stratification. A literature search was conducted following medical subject headings (MeSh), Emtree language, Decs, and text words related. We searched through MEDLINE (OVID), EMBASE (Scopus), LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 2021. Evidence acquisition was presented according to the PRISMA diagram. (3) Results: Preoperative risk factors for either muscle-invasive UTUC (≥pT2), extra urothelial recurrence (EUR), locally advanced disease, or high-risk UTUC can either be derived from ureteroscopic (URS) findings, urine cytology, URS biopsy, or from preoperative radiologic findings. It seems reasonable that LND may provide not only staging and prognostic information but also play a therapeutic role in selected UTUC patients. The patients who benefit the most from LND appear to be those with ≥ pT2 disease, because patients with tumors ≤ pT1 rarely metastasized to LNs. UTUC has characteristic patterns of lymphatic spread that are dependent on tumor laterality and anatomical location. Choosing the right patients for LND, designing and standardizing LND templates based on tumor location and laterality is critical to improve LN yield, survival outcomes, and to avoid under-staging or overtreatment. (4) Conclusions: Patients with muscle-invasive or non-organ-confined UTUC have an extremely high risk for disease recurrence and cancer-specific mortality (CSM). Preoperative factors and prediction models must be included in the UTUC management pathway in our clinical practice to improve the accurate determination of high-risk groups that would benefit from LND. We recommend offering LND to patients with ipsilateral hydronephrosis, cHG, cT1 at URS biopsy and renal sinus fat or periureteric fat invasion. The role of lymphadenectomy in conjunction with radical nephroureterectomy (RNU) is still controversial, given that it may result in overtreatment of patients with pTa-pT1 tumors. However, a clear benefit in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS) has been reported in patients with ≥pT2. We try to avoid LND in patients with cLG, cTa, and no ipsilateral hydronephrosis if the patient is expected to be compliant with the follow up schedule. There is still plenty of work to do in this area, and new molecular and non-invasive tests are necessary to improve risk stratification. Full article

The relationship between prostatic chronic inflammation (PCI) and prostate cancer (PCa) is unclear and controversial. Some authors reported that a history of chronic prostatitis may be correlated with PCa induction, while others associate chronic inflammation with less aggressive disease or consider inflammation as a possible protective factor against PCa. Four different types of prostatitis are known: bacterial acute prostatic inflammation, bacterial chronic prostatic inflammation, abacterial prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatic chronic inflammation. Prostatic inflammation is underestimated during daily clinical practice, and its presence and degree often go unmentioned in the pathology report of prostate biopsies. The goal of this report is to further our understanding of how PCI influences the biology of PCa. We investigated the main pathogenetic mechanisms responsible for prostatic inflammation, including the cellular response and inflammatory mediators to describe how inflammation modifies the prostatic environment and can lead to benign or malignant prostatic diseases. We found that prostatic inflammation might have a pivotal role in the pathogenesis of prostatic diseases. Details about PCI in all prostate biopsy reports should be mandatory. This will help us better understand the prostatic microenvironment pathways involved in PCa biology, and it will allow the development of specific risk stratification and a patient-tailored therapeutic approach to prostatic diseases. Full article