In a study from Madrid, patients from one centre were retrospectively reviewed, comparing those who had surgery for BPH in the first half of 1992 to that of 2002. The authors concluded that surgery was currently less common in older patients, and in patients who had received medical treatment for longer. They also found that open surgery was more common in those who required surgery, perhaps because the increase in prostate size was not suppressed by the medical therapy predominantly prescribed in the decade in question. OBJECTIVES: To compare the clinical profile (age, comorbidities, symptom severity, and incidence of acute urinary retention, AUR), the type and duration of medical treatment, and indications for surgery of patients undergoing surgery for benign prostatic hyperplasia (BPH) in 1992 and 2002 at one centre. PATIENTS AND METHODS: In this single‐centre, retrospective, cross‐sectional observational study, the medical history of all patients who had surgery for BPH in the first semester of 1992 (85) and 2002 (70) was reviewed. The preoperative clinical profile was determined by assessing age, main comorbidities, prostatic volume, maximum urinary flow rate and symptom severity. The type and duration of pharmacology for BPH was evaluated from the medical history and telephone contact with the patients. Indications for surgery, the method of operation and the weight of removed tissue (open adenectomy) or the volume of the resected tissue (transurethral resection) were obtained from the patients’ records and compared. Surgical complications in both groups were assessed, as was the average stay in hospital. RESULTS: In our institution, surgery for BPH decreased by 17.6% in the decade, with patients having surgery when older, at a mean ( sd ) of 69.1 (8.57) vs 72.3 (7.59) years, i.e. 3.1 years older ( P = 0.028), but with similar comorbidities. Reasons for surgery in 1992/2002, respectively, were AUR in 41/37%, and symptoms worsening in 48/51%. The few cases of haematuria and bladder stone were similarly distributed in both groups. Pharmacology for BPH was prescribed in 46% of patients in 1992, phytotherapy being the most common (89%), whereas in 2002, 82% ( P < 0.01) were treated, most of them with α‐adrenergic antagonists (79%). Open surgery was indicated in 18.8% of patients in 1992 (mean adenoma weight 73.8 g, sd 37.12) and in 28.6% in 2002 (79.8 g, sd 35.41; P = 0.625). The mean ( sd ) hospital stay was 8.9 (4.06) vs 5.0 (1.22) days in 1992 and 2002, respectively ( P < 0.01) for transurethral resection, and 14.1 (5.74) vs 8.7 (4.83) for open adenectomy ( P = 0.013). The complication rate was similar for both groups. CONCLUSIONS: Compared with 1992, fewer patients with BPH have surgery, when older and after receiving medical treatment for longer. The indications for surgery are similar. Significantly more patients had open surgery, perhaps because the progressive increase in prostate volume was not affected by the medical therapy used predominantly during this decade.

Urinary tract-associated diseases comprise a complex set of disorders with a variety of etiologic agents and therapeutic approaches and a huge global burden of disease, estimated at around 1 million deaths per year. These diseases include cancer (mainly prostate, renal, and bladder), urinary tract infections, and urolithiasis. Cell death plays a key role in the pathogenesis and therapy of these conditions. During urinary tract infections, invading bacteria may either promote or prevent host cell death by interfering with cell death pathways. This has been studied in detail for uropathogenic E. coli (UPEC). Inhibition of host cell death may allow intracellular persistence of live bacteria, while promoting host cell death causes tissue damage and releases the microbes. Both crystals and urinary tract obstruction lead to tubular cell death and kidney injury. Among the pathomechanisms, apoptosis, necroptosis, and autophagy represent key processes. With respect to malignant disorders, traditional therapeutic efforts have focused on directly promoting cancer cell death. This may exploit tumor-specific characteristics, such as targeting Vascular Endothelial Growth Factor (VEGF) signaling and mammalian Target of Rapamycin (mTOR) activity in renal cancer and inducing survival factor deprivation by targeting androgen signaling in prostate cancer. An area of intense research is the use of immune checkpoint inhibitors, aiming at unleashing the full potential of immune cells to kill cancer cells. In the future, this may be combined with additional approaches exploiting intrinsic sensitivities to specific modes of cell death such as necroptosis and ferroptosis. Here, we review the contribution of diverse cell death mechanisms to the pathogenesis of urinary tract-associated diseases as well as the potential for novel therapeutic approaches based on an improved molecular understanding of these mechanisms.

Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Background: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). Methods: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (β-CTX) were analysed. Results: Patients with RCC who died or progressed had higher baseline β-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline β-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that β-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. Conclusion: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Background: The improvement of absent or partial response in the medical treatment of erectile dysfunction (ED) has led to the development of minimally invasive new treatment modalities in the field of regenerative medicine. Methods: A literature review on stem cell therapy for the treatment of ED was performed. We searched for the terms “erectile dysfunction” and “stem cell therapy” in PubMed and Clinicaltrials.gov. Literature searching was conducted in English and included articles from 2010 to 2022. Results: New treatment modalities for ED involving stem cell therapy are not only conceived with a curative intent but also aim to avoid unnecessary adverse effects. Several sources of stem cells have been described, each with unique characteristics and potential applications, and different delivery methods have been explored. A limited number of interventional studies over the past recent years have provided evidence of a safety profile in their use and promising results for the treatment of ED, although there are not enough studies to generate an appropriate protocol, dose or cell lineage, or to determine a mechanism of action. Conclusions: Stem cell therapy is a novel treatment for ED with potential future applications. However, most urological societies agree that further research is required to conclusively prove its potential benefit.

Background: Despite the term acute kidney injury (AKI), clinical biomarkers for AKI reflect function rather than injury and independent markers of injury are needed. Tubular cell death, including necroptotic cell death, is a key feature of AKI. Cyclophilin A (CypA) is an intracellular protein that has been reported to be released during necroptosis. We have now explored CypA as a potential marker for kidney injury in cultured tubular cells and in clinical settings of ischemia-reperfusion injury (IRI), characterized by limitations of current diagnostic criteria for AKI. Methods: CypA was analyzed in cultured human and murine proximal tubular epithelial cells exposed to chemical hypoxia, hypoxia/reoxygenation (H/R) or other cell death (apoptosis, necroptosis, ferroptosis) inducers. Urinary levels of CypA (uCypA) were analyzed in patients after nephron sparing surgery (NSS) in which the contralateral kidney is not disturbed and kidney grafts with initial function. Results: Intracellular CypA remained unchanged while supernatant CypA increased in parallel to cell death induction. uCypA levels were higher in NSS patients with renal artery clamping (that is, with NSS-IRI) than in no clamping (NSS-no IRI), and in kidney transplantation (KT) recipients (KT-IRI) even in the presence of preserved or improving kidney function, while this was not the case for urinary Neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, higher uCypA levels in NSS patients were associated with longer surgery duration and the incidence of AKI increased from 10% when using serum creatinine (sCr) or urinary output criteria to 36% when using high uCypA levels in NNS clamping patients. Conclusions: CypA is released by kidney tubular cells during different forms of cell death, and uCypA increased during IRI-induced clinical kidney injury independently from kidney function parameters. Thus, uCypA is a potential biomarker of kidney injury, which is independent from decreased kidney function.