Patients with renal transplant and moderate-to-severe LUTS benefit from urodynamic evaluation and early transurethral resection of the prostate.

PURPOSE: To assess long-term renal function and micturition pattern of males submitted to transurethral resection of the prostate (TURP) for moderate-to-severe lower urinary tract symptoms (LUTS) after renal transplantation (RT). To investigate the role of clinical and urodynamic (UD) parameters for bladder outlet obstruction (BOO) diagnosis in these patients. METHODS: Retrospective data analysis of ≥ 50 years old patients who underwent RT between 01/2005 and 12/2016. Patients with moderate-to-severe LUTS after RT who underwent a urologic evaluation and a UD study were included. TURP was performed in case of BOO diagnosis. Kidney function and micturition patterns were evaluated before, 3, 12, 24, 36, and 48 months after TURP. Predictors of BOO were assessed at univariable and multivariable logistic regression models. Statistical analysis was performed with STATA16. RESULTS: 233 male patients ≥ 50 years underwent RT. 71/233 (30%) patients developed voiding LUTS. 52/71 (73%) patients with moderate-to-severe LUTS underwent UD. TURP was performed in 36/52 (69%) patients, with BOO diagnosis. Median (interquartile range) follow-up was 108 (75-136) months. Maximum flow at flowmetry (Qmax), International Prostate Symptom Score and post-voided residual volume improved significantly after surgery. Serum creatinine decreased and glomerular filtration rate improved significantly at follow-up, especially when TURP was performed ≤ 6 months from RT. At the multivariable model, bladder capacity ≥ 300 mL (OR = 1.74, CI 95% 1.03-3.15, p = 0.043) and detrusor pressure at Qmax (OR = 2.05, CI 95% 1.48-3.02, p = 0.035) were the independent predictors of BOO. CONCLUSION: RT patients with moderate-to-severe LUTS at risk for BOO and graft failure are better identified by UD than clinical parameters. Bladder capacity and voiding pressure are key for the early diagnosis of BOO.

Gender-Related Approach to Kidney Cancer Management: Moving Forward.

Men are more frequently diagnosed with kidney cancer than women, with a more aggressive histology, larger tumors, a higher grade and stage, and worse oncological outcomes. Smoking habits and sex steroid hormones seem to have a possible role in explaining these gender disparities. Moreover, the expression of genes involved in tumor growth and immune response in kidney cancer varies between men and women, having an impact on the gender-related response to oncological therapy, such as anti-angiogenic drugs and immunotherapy. Recent advances have been made in our understanding of the molecular and genetic mechanisms involved in kidney cancer, which could partially explain the gender differences, and they are summarized in this paper. However, other key mechanisms, which fully clarify the striking clinical gender-related differences observed in kidney cancer, are not completely understood at present. We reviewed and summarized the most relevant publications about the relationship between gender and kidney cancer. Efforts should be made to progress in bench and clinical research on gender-related signatures and disparities, and their impact on the clinical management of kidney cancer.

The Bladder EpiCheck Test as a Non-Invasive Tool Based on the Identification of DNA Methylation in Bladder Cancer Cells in the Urine: A Review of Published Evidence.

Recently, there has been a great effort to develop tests based on non-invasive urinary biomarkers (NMIBCs). These tests are based on the fact that NMIBCs are heterogeneous at the molecular level and can be divided into different molecular groups useful to predict prognosis and response to treatment. The assessment of epigenetic alterations, such as DNA methylation, represents a promising cancer biomarker. DNA methylation is an epigenetic modification that affects gene expression without modifying the DNA sequence. Several studies have highlighted the presence of methylated loci in the context of bladder cancer, indicating its potential application as a diagnostic and prognostic biomarker. One of the novel assays based on a DNA methylation profile, the Bladder EpiCheck, analyzes DNA from spontaneous urine, detecting disease-specific DNA methylation patterns in bladder cancer patients. This test, due to its non-invasive nature and highly promising performance could, in future, become an invaluable tool in the follow-up of bladder cancer patients. Potential new applications could include diagnosis and surveillance of upper-tract disease, for the replacement of invasive testing and ureteroscopy.

Metabolic syndrome and bladder cancer.

Metabolic syndrome (MetS) is a widely diffused dysmetabolism, well known to be associated with an increased cardiovascular risk. However, a growing burden of evidence links MetS with several malignancies, potentially influencing the onset, progression, and therapeutic response. In this work, we critically explored the relationship between MetS and bladder cancer through a narrative review, researching the most recent literature on the topic using PubMed, MEDLINE, and EMBASE. We found that the current evidence on the subject is heterogeneous and inconsistent, making it difficult to draw definitive conclusions. Furthermore, since MetS would be a modifiable oncological risk factor, more high-quality data is needed for tailored treatment of bladder cancer.

Checkpoint Inhibition in Bladder Cancer: Clinical Expectations, Current Evidence, and Proposal of Future Strategies Based on a Tumor-Specific Immunobiological Approach.

In contrast with other strategies, immunotherapy is the only treatment aimed at empowering the immune system to increase the response against tumor growth. Immunotherapy has a role in the treatment of bladder cancer (BC) due to these tumors' high tumor mutational burden (TMB) and mostly prominent immune infiltrate. The therapy or combination has to be adjusted to the tumor's immunobiology. Recently, a new class of immunotherapeutic agents, immune checkpoint inhibitors (ICI), has shown potential in increasing treatment chances for patients with genitourinary cancers, improving their oncological outcomes. The clinical efficacy of ICI has been shown in both the first-line treatment of cisplatin-ineligible patients, with programmed death ligand 1 (PD-L1)-positive tumors (atezolizumab, pembrolizumab), and in second-line settings, for progression after platinum-based chemotherapy (atezolizumab, pembrolizumab, and nivolumab for FDA and EMA; durvalumab and avelumab for FDA alone). Predicting the response to ICI is important since only a subset of patients undergoing ICI therapy develop a concrete and lasting response. Most of the patients require a different therapy or therapy combination to achieve tumor control. The cancer immunity cycle provides a conceptual framework to assist therapy selection. Biomarkers to predict response to ICI must identify where the cancer immunity cycle is disrupted. We reviewed the current knowledge on ICI treatment in BC, going from basic science to current data and available clinical evidence. Secondly, a critical analysis of published data is provided, and an original panel of biomarkers able to predict response to ICI treatment, based on tumor-specific immune profiling, is proposed.

Successful Treatment of Vesicovaginal Fistulas via an Abdominal Transvesical Approach: A Single-center 50-yr Experience.

BACKGROUND: A vesicovaginal fistula (VVF) is an abnormal communication between bladder and vagina, as a result of traumatic events to the female pelvis. A VVF is a rare event and challenging to cure. Successful treatment can be achieved through an abdominal approach, especially in complex or recurrent cases. This approach has been used in our institution as the procedure of choice for the past 50yr. OBJECTIVE: To analyze the results of the management of VVFs in our institution and to highlight the key points for success. DESIGN, SETTING, AND PARTICIPANTS: A total of 138 patients with VVFs have been treated in our institution between 1969 and 2019. Up to now, this is the largest series reported so far on abdominal treatment of VVFs in the developed world. INTERVENTION: an abdominal transvesical approach has been performed as the procedure of choice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: to evaluate the factors influencing the success rate of the abdominal approach at the first closure attempt. Statistical analysis was performed using STATA software. RESULTS AND LIMITATIONS: In total, 124 (90%) patients were submitted to transabdominal repair (89 extraperitoneal; 71.8%), 113 (91.1%) presented with a VVF not associated with another fistula, and 36 (29.0%) had undergone previous unsuccessful treatments elsewhere. Successful closure was obtained in 111/118 (94.1%) patients at the first attempt, excluding external noncontinent urinary diversions. Follow-up was possible in 95 (76.6%) patients; 91 (95.8%) patients were dry. Statistical analysis showed a significant association between fistula size and length, and VVF site in the bladder and extraperitoneal approach. Success rate decreased with the number of previous attempts and did not vary with VVF etiology. CONCLUSIONS: The abdominal approach for the treatment of VVF has a high success rate. Standardization of the technique, identification of surgical key points, and centralization of care in centers with experience are critical. PATIENT SUMMARY: A vesicovaginal fistula (VVF) is a rare clinical condition, with a high impact on patients' quality of life. We report a large series of VVFs treated in our institution in the past 50yr. Key factors for success include proper surgical technique and centralization of care in centers with high experience.

Spotlight on gender-specific disparities in bladder cancer.

Men are at a higher risk of developing bladder cancer, but women present with more advanced disease and have more unfavourable outcomes. Although epidemiologic and genetical studies have underlined the multifactorial aetiology and gender-related differences of bladder cancer, there is lack of evidence-based recommendation for gender-specific management of bladder cancer. We summarize the evidence and most recent findings on gender-specific differences in bladder cancer incidence, diagnosis, treatment and outcome, spotlighting the gender disparities in genetic and hormonal risk factors, pelvic anatomy, diagnostic setting and surgical choices. We reviewed the literature published on PubMed between 1981 and 2018. Males have a threefold to fourfold higher risk of bladder cancer as compared to females; however, women have higher stage-for-stage mortality, being diagnosed with more advanced disease, mostly due to a delay in haematuria evaluation. Numerous studies indicate an increased risk of disease recurrence or progression in women with non-muscle-invasive bladder cancer treated with trans-urethral resection, with or without intravesical chemotherapy or immunotherapy, compared to males. In particular, recent molecular evidence show that there is an excess of female Ta mutant tumours. At the time of radical cystectomy, women have a significantly longer length of hospital stay, operative time, higher blood loss and higher 90-day mortality and perioperative complication rate. Moreover, females are less likely to receive a continent diversion. Future research should guarantee greater inclusion of women in trials and focus on improving the effectiveness of therapies in women, perhaps exploring different therapeutic approaches in men and women. Specific data on functional and oncological outcomes can be analysed to define predictive factors able to guide the surgeon in decisions based on evidence. It is urgently needed to limit gender-related discrepancies in early diagnosis and treatment of bladder cancer. Public awareness and bladder cancer female patients' consciousness on gender inequalities must be similarly uprisen.

Incidence and Treatment of Incarcerated Trocar-Site Hernias After Robotic Surgery: Presentation of Three Cases.

Background: Trocar-site hernias (TSHs) are an uncommon but potentially severe complication of robot-assisted urologic surgery, with an incidence of incarcerated hernias varying from 0.4% to 0.66%. Currently, there are no standardized guidelines on trocar site fascial closure. Although it is widely recommended to close the midline 12-mm port site, there is no agreement on the need for fascial closure of lateral port sites, especially if ≤12 mm. Cases Presentation: We report three cases of incarcerated intestinal TSHs in the past 10 years in our institution. All were from lateral abdominal ports (two 12 and one 8 mm), after robot-assisted radical prostatectomy. Patients were Caucasian and from 60 to 71 years; symptoms varied widely from obstinate hiccups, abdominal distention with fever, to acute abdomen. In all cases reduction of the herniated loop from the outside, using a minilaparotomy over the port site, was safe and effective. However, in one case bowel resection for bowel ischemic necrosis was necessary. No specific clinical risk factors could be identified in our cases. Conclusion: Incarcerated TSH after robotic urologic surgery may arise from any trocar site, regardless of size and location. This could be treated effectively with a minilaparotomy over the trocar site, to avoid more serious life-threatening consequences such as bowel necrosis and perforation. No risk factor seems to be predictive of TSHs.