Twenty-Four-Month Efficacy of Ureteroureterostomy Combined With Unilateral Nephrostomy Following Radical Cystectomy.

Introduction The purpose of this study was to evaluate the 24-month outcomes of ureteroureterostomy combined with unilateral nephrostomy following radical cystectomy in patients with muscle-invasive bladder cancer (BC). Materials and methods This single-center study with prospectively collected data with retrospective data analysis was carried out between December 2018 and November 2021 and enrolled 36 patients, who underwent radical cystectomy combined with ureteroureterostomy and unilateral nephrostomy. Regular renal function assessment was carried out using serum creatinine and estimated glomerular filtration rate (eGFR), and postoperative complications, endoscopic, ultrasound, and other radiological study findings were evaluated. The follow-up of the patients was carried out over a period of 24 months. Results After completion of the 24-month follow-up, the renal function proved to be slightly improved (mean serum creatinine and eGFR values of 1.38±0.72 mg/dL and 55.9±21.87 mL/min) compared to the first-year results (1.41±0.54 mg/dL and 52.10±19.64 mL/min). However, this improvement is statistically not significant (p=0.44, p=0.30). The 24-month follow-up imaging findings remained stable in 97.22% of patients compared to the first-year results, with preservation of bilateral ureteric dilatation and grade 1 dilatation of the non-drained kidney. No case of acute pyelonephritis was recorded after the completion of the second year of follow-up, in comparison to the eight patients (22.22%) of the 12-month follow-up, who suffered acute pyelonephritis. After completing of the 24-month follow-up, one patient was excluded from further analysis, due to the placement of a second permanent percutaneous nephrostomy in the non-drained kidney, due to ureteroureterostomy stenosis with consecutive hydronephrosis in the contralateral kidney and acute renal failure. No case of anastomotic leak was observed. Conclusions The function of the ureteroureterostomy combined with unilateral nephrostomy is proven to be a safe method of urinary diversion (UD) at 24 months, with minimal and easily manageable complications. Only one case of stenosis of the ureteroureterostomy with consecutive acute renal failure due to hydronephrosis in the non-drained kidney was observed. The renal function remained stable.

Risk for Arterial Thromboembolic Events (ATEs) in Patients with Advanced Urinary Tract Cancer (aUTC) Treated with First-Line Chemotherapy: Single-Center, Observational Study.

Arterial thromboembolism has been associated with cancer or its treatment. Unlike venous thromboembolism, the incidence and risk factors have not been extensively studied. Here, we investigated the incidence of arterial thromboembolic events (ATEs) in an institutional series of advanced urinary tract cancer (aUTC) treated with cytotoxic chemotherapy. The ATE definition included peripheral arterial embolism/thrombosis, ischemic stroke and coronary events. A total of 354 aUTC patients were analyzed. Most patients (95.2%) received platinum-based chemotherapy. A total of 12 patients (3.4%) suffered an ATE within a median time of 3.6 months from the start of chemotherapy. The most frequent ATE was ischemic stroke (n = 7). Two ATEs were fatal. The 6-month and 24-month incidence were 2.1% (95% confidence interval [CI]: 0.9-4.1) and 3.6% (95% CI: 1.9-6.2), respectively. Perioperative chemotherapy increased the risk for ATE by 5.55-fold. Tumors other than UTC and pure non-transitional cell carcinoma histology were also independent risk factors. No association with the type of chemotherapy was found. Overall, ATEs occur in 4.6% of aUTC patients treated with chemotherapy and represent a clinically relevant manifestation. Perioperative chemotherapy significantly increases the risk for ATE. The role of prophylaxis in high-risk groups should be prospectively studied.

Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy.

BACKGROUND: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. PATIENTS AND METHODS: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. RESULTS: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. CONCLUSION: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

Established and recent developments in the pharmacological management of urolithiasis: an overview of the current treatment armamentarium.

Introduction: Urolithiasis is a common, highly recurrent disease with increasing prevalence worldwide. There are many dietary and pharmacological measures to prevent kidney stones.Areas covered: Herein, the authors explore medical expulsive therapy as well as pharmacological therapies to prevent/treat urolithiasis.Expert opinion: All stone formers should be advised to increase their fluid intake sufficiently to achieve a urine volume of at least 2.5 L/day. In the case of hypercalciuria, a thiazide diuretic should be prescribed while in cases of hypocitraturia, potassium citrate should be given. In the case of hyperoxaluria, the treatment depends on the type of hyperoxaluria. Pyridoxine or calcium supplements with a meal can be offered. For uric acid stone formers, alkali therapy is the standard of care whereas allopurinol can be beneficial in hyperuricosuric stone formers. For cystine stone formers, increased fluid intake, restriction of sodium and animal protein ingestion, and urinary alkalinization are the standard therapies used. Cystine binding thiol drugs such as tiopronin and D-penicillamine are reserved for patients where a conservative approach fails. For struvite stone formers, optimal management is the complete stone removal. Acetohydroxamic acid may be offered only after surgical options have been exhausted, for patients with residual stones but it has many side effects.

Is there an appropriate strategy for treating co-morbid irritable bowel syndrome and bladder pain syndrome?

INTRODUCTION: Two of the most frequent components of chronic pelvic pain syndrome (CPPS) are irritable bowel syndrome (IBS) and bladder pain syndrome (BPS), characterized by considerable overlapping symptoms and pathophysiology. Currently, its management is challenging meaning there is high the demand for novel efficient therapeutics to aid patient care and to tackle the socioeconomic burden of IBS and BPS. As there are presently no sufficient treatment strategies, identifying the mechanisms that result in their main symptoms is the opportunity for developing appropriate therapies. Areas covered: Herein, the authors explore the potential common treatment strategies for co-morbid IBS and BPS and highlight the absolute need for further research of these deliberating clinical entities. Expert opinion: In the future, the authors summise that the discovery of predictive molecular biomarkers combined with clinical phenotypic categorization will likely allow for more definitive differentiation of patients and thus for better treatment options. Furthermore, it has been suggested that effective IBS treatment strategies would be of great value to co-morbid IBS and BPS therapy.

Perspectives on the current and emerging chemical androgen receptor antagonists for the treatment of prostate cancer.

INTRODUCTION:  Prostate cancer is the most common cancer in men. Regardless of the initial treatment of localized disease, almost all patients develop castration resistant prostate cancer (CRPC). A better understanding of the molecular mechanisms behind castration resistance has led to the approval of novel oral androgen receptor (AR) antagonists, such as enzalutamide and apalutamide. Indeed, research has accelerated with numerous agents being studied for the management of CRPC. Areas covered: Herein, the authors present currently used and emerging AR antagonists for the treatment of CRPC. Emerging agents include darolutamide, EZN-4176, AZD-3514, and AZD-5312, apatorsen, galeterone, ODM-2014, TRC-253, BMS-641988, and proxalutamide. Expert opinion: Further understanding of the mechanisms leading to castration resistance in prostate cancer can reveal potential targets for the development of novel AR antagonists. Current novel agents are associated with modest clinical and survival benefit, while acquired resistance and safety issues are under continuous evaluation. The combination of AR antagonists used and ideal sequencing strategies are key tasks ahead, along with the investigation of molecular biomarkers for future personalized targeted therapies. In the future, the challenge will be to determine an AR antagonist with the best combination of outcome and tolerability.

Bridging pharmacotherapy and minimally invasive surgery in interstitial cystitis/bladder pain syndrome treatment.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful and debilitating clinical entity which is challenging to diagnose and even more difficult to treat. Unfortunately, none of the existing oral and intravesical medications have been established as effective and therefore relevant research is ongoing. Areas covered: In this review, the authors present established and emerging treatment options for IC/BPS in terms of medication and minimal invasive procedures. Both American and European Urological Association Guidelines recommend multimodal behavioral techniques alongside oral (e.g. amitriptyline and pentosan polysulfate sodium) or minimally invasive treatments (e.g. dimethyl sulfoxide, botulinum toxin, chondroitin sulfate, triamcinolone, hyaluronic acid, and lidocaine). Novel treatment modalities include immunomodulating drugs, stem cell therapy, nerve growth factor, and ASP6294. Expert opinion: IC/BPS is still a pathophysiological enigma with multifactorial etiopathogenesis that may be controlled but not completely cured. Patient-tailored phenotype-directed multimodal therapy is the most promising treatment strategy. Combined phenotypic categorization with specific biomarkers could help toward better treatment.

Paraffinoma, siliconoma and Co: Disastrous consequences of failed penile augmentation-A single-centre successful surgical management of a challenging entity.

The purpose of this study was to present our series of patients with disastrous consequences of failed penile self-augmentation and suggested surgical reconstruction. Ten patients with median age of 23 years and a variety of penile and scrotal deformities due to injections of several substances had undergone successful surgical reconstruction of external genitalia. The injections were self-performed in nine cases and the patients reported from 4 to 20 substance injections throughout the penile shaft. Three patients presented with fibrotic scirrhous masses in their scrotum, although they did not report any injections in scrotal area. All patients underwent extended penile-shaft skin excision, while all palpable scrotal lesions were removed in one-by-one fashion, as an attempt to destroy the less possible scrotal tissue. All patients were discharged on first post-operative day and reassessed at 2 months post-operatively. As a result, penile self-augmentation with injected substances may cause severe complications. Our proposed single-staged procedure seems safe and effective.

Apalutamide: the established and emerging roles in the treatment of advanced prostate cancer.

INTRODUCTION: Prostate cancer (PCa) is the most common cancer in elderly males. Androgen deprivation therapy (ADT) is still the cornerstone of initial treatment; however, the vast majority of patients develop castration-resistant prostate cancer (CRPC). Several studies with numerous androgen receptor (AR)-directed agents have emerged since the approval of abiraterone acetate and enzalutamide. One of these agents is apalutamide, which seems to be a promising AR antagonist for the treatment of CRPC. Areas covered: The authors review Phase I, II, and III studies for apalutamide, in a large spectrum of PCa (from low-risk to metastatic CRPC [mCRPC]) patients as sole treatment or in the setting of combined therapy. Expert opinion: Apalutamide is an oral, investigational, AR antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets. It has shown favorable safety profile and therapeutic index in Phase I studies, good tolerance and efficacy in patients with high-risk CRPC in Phase II studies. Also, results were promising in a recent phase III study in patients with non-mCRPC who were at high risk for the development of metastasis. These data may offer potential advantages over the second-generation antiandrogens.

The Impact of Technique Standardization on Total Operating and Fluoroscopy Times in Simple Endourological Procedures: A Prospective Study.

PURPOSE: To present the positive impact of technique standardization on successful outcome, fluoroscopy, and total operating time (TOT) shortening in a prospective study. METHODS: Six experienced endourologists participated. To assess whether the adaptation of standardized surgical steps improved their methodology with time, 253 patients were prospectively divided in three consecutive 1-month groups. Patients underwent stent placement and exchange and total operating and fluoroscopy times (FTs) were recorded. All surgeons were unaware of their mean recorded results until the end of the study. At the end of the third month, we evaluated if the suggested technique standardization established a decrease for both FT and TOT. Statistical significance was set to p < 0.05. RESULTS: Total operating and FTs were significantly reduced with time between all groups of patients. For stent placement, TOT showed significant reduction between Groups A and C (p < 0.001), while between other group comparisons did not reach significance. FT showed a significant reduction (p < 0.001) in all group comparisons. For stent exchange, TOT reached significant improvement (p = 0.003) between Groups A and C, whereas between other groups was insignificant. FT improvement was significant between Groups A and C (p < 0.001) and Groups B and C (p < 0.001), but insignificant between Groups A and B. CONCLUSIONS: Even in experienced hands, the adaptation of technique standardization results in significant decrease of total operating and FTs and it is independent from feedback regarding their time performance.

Modified S-ileal neobladder for continent urinary diversion: functional and urodynamic results after 20 years of follow-up.

OBJECTIVE: To report continence and urodynamic findings after radical cystectomy and urinary diversion with modified S-ileal neobladder between January 1993 and January 2013. PATIENTS AND METHODS: 181 patients were enrolled. Continence status, reservoir sensation, compliance, capacity and activity were assessed. RESULTS: Daytime continence was reported by 88.0, 98.4 and 99.2%, while nighttime continence was reported by 70.2, 94.0 and 95.8% of our patients at 6 months, 5 years and 20 years, respectively. Enterocystometric capacity and maximum reservoir pressure were 366 vs. 405 ml and 502 ml, and 29 vs. 18 and 11 cm H2O, at 6 months, 5 years and 20 years, respectively. Median post-void residual urine volume was 32 ml at 6 months, 50 ml at 5 years and 120 ml at 20 years. CONCLUSIONS: The modified S-ileal neobladder technique has a very good long-lasting functional outcome, with high day- and nighttime continence levels as well as high acceptability rates from our patients.

Insight into long-term histological, proliferative and apoptotic modifications in ileal orthotopic neobladder and conduit mucosa.

AIMS AND BACKGROUND: To assess the long-term histological, apoptotic and proliferating alterations of the intestinal mucosa of ileal conduits and orthotopic neobladders. METHODS: Fifty patients (46 males, 4 females), aged 52-78 years, who underwent urinary diversion with either ileal orthotopic neobladder (group ON, 20 patients) or conduit (group IC, 30 patients) from 2001 to 2005, were included in this prospective study. Ileal samples were collected during surgery (controls) and by random mucosal biopsies 6, 12, 24, 36 and 48 months later. Histological (villi height, crypt depth, eosinophil cell count), proliferation (Ki67 immunochemistry), and apoptotic (Bcl-2 immunochemistry, TUNEL) parameters were assessed. RESULTS: During the 4-year follow-up, we recorded progressive villi area, height and crypt depth reduction, mucosa flattening, and inflammatory and eosinophilic infiltration. Villi height: crypt depth ratio showed a statistically significant difference (P < 0.05) between the two groups from the 6th month. Dysplasia, metaplasia, and neoplasia were not observed. Bcl-2 values showed a progressive increase until 24 months in group ON and 12 months in group IC, followed by a decline thereafter. Ki-67 values showed a progressive increase after 6 months in group ON and an increase until 24 months followed by a decline thereafter in group IC. TUNEL showed two peaks, at 24 and 48 months. CONCLUSIONS: Histological adaptation was revealed in both groups, with statistically significant differences in favor of orthotopic substitution. Proliferative and apoptotic pathways are implicated as demonstrated by relevant modifications of Bcl-2, Ki-67 and TUNEL, in accord with the histological adaptation.