Immunotherapy-induced adverse events in metastatic renal cell carcinoma: A case of rapid response and complex challenges.

A 55-year-old woman with dyspnea was diagnosed with a 9.5cm left renal clear cell carcinoma and extensive metastatic disease. Initial treatment with Sunitinib was effective but discontinued due to severe dermatitis. Nivolumab therapy led to complete metastasis resolution and consequently nephrectomy was performed at 12 months. Postoperatively, she developed Vogt-Koyanagi-Harada-like disease, necessitating Nivolumab suspension and vision improvement with corticosteroids. After 24 disease-free months, a new contralateral renal lesion and pulmonary metastases were identified, prompting cabozantinib treatment. This resulted in clinical improvement and a partial response at the first follow-up.

Septic Shock After Intravesical Therapy With Bacillus Calmette-Guerin: A Case Report of a Rare Life-Threatening Complication.

Intravesical therapy with Bacillus Calmette-Guerin (BCG) is the mainstay treatment for high-risk non-muscle invasive bladder cancer. The side effects are usually local and mild. Systemic dissemination of BCG is rare, typically develops soon after instillation, and may present as a severe life-threatening condition. We present a case of a 49-year-old man under chronic haemodialysis who developed septic shock after the first BCG maintenance instillation for bladder carcinoma in situ (CIS). Supportive measures and empiric broad-spectrum antibiotic therapy were promptly started after sample collection for cultures. Lastly, the recurrence of fever raised the initial suspicion of BCG dissemination. The diagnosis was confirmed by the identification of the Mycobacterium tuberculosis complex in blood samples collected and anti-tuberculosis therapy was then initiated. We would like to highlight the need for early recognition of a systemic BCG infection and the importance of starting anti-tuberculosis treatment as early as possible.

Predictive factors for successful testicular biopsy.

INTRODUCTION: Infertility, the inability to conceive, constitutes a major problem in modern societies. It affects 10 to 15 percent of couples in the United States. Evaluation of infertile men is usually complex and often demands a testicular biopsy. MATERIALS AND METHODS: We reviewed all azoospermic men submitted to testicular biopsy, in our center, during infertility investigation between January 2015 and December 2021. RESULTS: A total of 117 patients with a mean age of 36.5 was considered. Biopsy was positive, as defined by the presence of viable spermatozoids by microscopy, in 48.7% of patients (n = 57). Patients were divided in two separate groups based on positive (PB) or negative biopsy (NB) and compared. PB-group had normal serum total testosterone levels and higher than NB-group (3.7 ng/mL vs. 2.85 ng/mL, p = 0.021), and normal serum FSH levels and lower than NB-group (6.0 mIU/mL vs. 16.0 mIU/mL, p < 0.001). The groups were similar concerning serum LH levels (3.9 mIU/mL vs. 6.3 mIU/mL, p = 0.343. CONCLUSIONS: Predicting outcomes of testicular biopsy is a difficult task. Our study found that men with normal testicular volume, normal levels of testosterone and FSH and those with type 1 diabetes mellitus had a higher probability of positive testicular biopsy.

Surveillance as a safe and effective option for treatment of stage I seminoma.

Introdubction: Stage I seminoma has a very good prognosis, yet approximately 15% have subclinical metastatic disease and will relapse after orchidectomy alone. Several management approaches have been investigated. We aimed to evaluate the clinical outcomes of real-world patients with stage I seminoma, analysing prognostic factors influencing treatment choice and oncological outcomes. METHODS: Retrospective, single institution study, with 55 patients diagnosed with clinical stage I seminoma between 2007 and 2020. Selected patients were analysed regarding three management approaches - surveillance, adjuvant radiotherapy and adjuvant carboplatin AUC7. Overall survival and progression-free survival outcomes were analysed. Predictors of treatment choice were determined, and predictors of recurrence were analysed in patients on active surveillance. RESULTS: The median follow-up time was 91 months (13-165). Overall survival at 10 years was 98.2%. Stage I seminoma patients had a 1-, 3- and 10-year progression free survival of 98%, 94% and 89%, respectively. Three-year progression free survival was 92.0% for those on active surveillance (IC95%, 91.5-92.5%), 95.2% for carboplatin (IC95%, 94.8-95.6%) and 100% for those on adjuvant radiotherapy (p > 0.05). All relapses on active surveillance protocols occurred during the first 24 months. Overall, 43% of patients who underwent adjuvant treatment reported adverse effects of therapy, with higher incidence on radiotherapy group (63%). CONCLUSIONS: Stage I seminoma have excellent prognosis, high cure rates, and low treatment-associated morbidity. Active surveillance is a safe modality when applied to selected patients. Adjuvant radiotherapy and adjuvant chemotherapy with carboplatin show similar results, with fewer adverse effects on chemotherapy arm.

Benefits and Harms of Benign Prostatic Obstruction Treatments in Renal Transplanted Patients.

CONTEXT: In an increasingly ageing transplant population, timely management of benign prostatic obstruction (BPO) is key to preventing complications that result in graft dysfunction or compromise survival. OBJECTIVE: To evaluate benefits/harms of BPO treatments in transplant patients by reviewing current literature. EVIDENCE ACQUISITION: A computerised bibliographic search of Medline, Embase, and Cochrane databases was performed for studies reporting outcomes on BPO treatments in transplanted patients. EVIDENCE SYNTHESIS: A total of 5021 renal transplants (RTs) performed between 1990 and 2016 were evaluated. BPO incidence was 1.61 per 1000 population per year. Overall, 264 men underwent intervention. The mean age was 58.4 yr (27-73 yr). In all, 169 patients underwent surgery (n = 114 transurethral resection of the prostate [TURP]/n = 55 transurethral incision of the prostate [TUIP]) and 95 were treated with an un-named alpha-blocker (n = 46) or doxazosin (n = 49). There was no correlation between prostate volume and treatment modality (mean prostate size = 26 cc in the surgical group where reported and 48 cc in the medical group). The mean follow-up was 31.2 mo (2-192 mo). The time from RT to BPO treatment was reported in six studies (mean: 15.4 mo, range: 0-156 mo). The time on dialysis before RT was recorded in only three studies (mean: 47.3 mo, range: 0-288 mo). There was a mean improvement in creatinine after intervention from 2.17 to 1.77 mg/dl. A total of 157 men showed an improvement in the International Prostate Symptom Score (from 18.26 to 6.89), and there was a significant reduction in postvoid residual volume in 199 (mean fall 90.6 ml). Flow improved by a mean of 10 ml/s following intervention in 199 patients. Complications included acute urinary retention (4.1%), urinary tract infections (8.4%), bladder neck contracture (2.2%), and urethral strictures (6.9%). The mean reoperation rate was 1.4%. CONCLUSIONS: Current literature is heterogeneous and of low-level evidence. Despite this, alpha-blockers, TUIP, and TURP showed a beneficial increase in the peak urinary flow and reduced symptoms in transplants patients with BPO. Improvement in the mean graft creatinine was noted after intervention. Complications were under-reported. A multicentre comparative cohort study is needed to draw firm conclusions about the ideal treatment for BPO in RT patients. PATIENT SUMMARY: In this report, we looked at the outcomes for transplant patients undergoing medical or surgical management of benign prostatic obstruction. Although the literature was very heterogeneous, we found that medical management and surgery with transurethral resection/incision of the prostate are beneficial for improving urinary flow and bothersome symptoms. We conclude that further prospective studies are required for better clarity about timing and modality of intervention in transplant patients.

Seminal human papillomavirus infection: a narrative review.

BACKGROUND: Human papillomavirus (HPV) infection is one of the most prevalent sexually transmitted infections that can lead to malignant pathologies as well as fertility problems. The aim of this study was to evaluate the prevalence of HPV infection in males, its impact on semen parameters, and reproductive consequences. We also evaluated potential measures that could prevent negative outcomes of HPV infection in males. METHODS: A systematic literature search using PubMed/Medline and Embase databases was performed to search for English articles published until July 2023. We explored three different aspects: (1) prevalence of HPV semen infection and its impact on seminal parameters; (2) the relationship between HPV semen infection and infertility risk and reproductive outcomes; and (3) potential measures that could prevent the negative outcomes related to HPV seminal infection. The identified studies were first screened and assessed independently by one author, and then validated by two additional authors. Data were extracted from 19 studies. RESULTS: The prevalence of seminal HPV infection was higher among infertile males. In addition to controversies about the real interference of seminal HPV infection on sperm parameters, a growing number of studies have demonstrated a correlation between unexplained infertility and seminal HPV infection. Semen HPV infection is also associated with lower rates of pregnancy and higher rates of miscarriage. Prevention measures such as HPV vaccination seem promising. CONCLUSION: Further studies are required to confirm not only the association between HPV infection and reproductive outcomes but also the benefit of preventive measures.

C reactive protein/Albumin ratio as predictor of prognosis in castration resistant metastatic prostate cancer.

OBJECTIVE: To assess the association of C reactive protein/Albumin ratio (CAR) with progression free survival (PFS) and overall survival (OS) in castration resistant metastatic prostate cancer (mCRPC) patients. MATERIALS AND METHODS: A transversal study was conducted, including all patients diagnosed with mCRPC within a Central Hospital Urological Oncology consultation between December 2019 and December 2021 (n = 178) and that were submitted to systemic therapy. CRP and albumin results were collected at the beginning of the systemic treatment for mCRPC in 103 patients and, in 75 patients already under treatment at the start of the study, on that occasion (December 2019). All patients were then followed. CAR was correlated with PFS and OS. OS and PFS were measured from the day the CRP and Alb were collected until the event of interest or the final date of follow-up. The sample was divided in two groups according to an optimal cutoff point found in a ROC curve. RESULTS: The sample showed a median age of 75.76 ± 9.17 years old. Using a cut-off point of 0.22, patients with a CAR ≤ 0.22 (63.2%) showed, compared to CAR > 0.22, longer PFS (15.92 vs. 9.46 months, r = -0.13, p < 0.05) and OS (p = < 0.05, 25,72 vs. 15.79 months, r = -0,24, p < 0.05). Better OS in patients with CAR ≤ 0.22 vs > 0.22 was detected on both the group evaluated at the beginning of systemic treatment (26.96 vs 17.63 months, p < 0.05) and the group of patients already under treatment (23.90 vs 11.54 months, p < 0.05). Dividing the sample according to the first line treatment chosen, we found OS of 26.25 vs 5.9 months (p < 0.05), 27.71 vs 22.57 months (p < 0.05) and 27.36 vs 23.75 months (p = 0.12), for docetaxel, abiraterone and enzalutamide, respectively. CONCLUSIONS: According to this study, higher values of CAR are associated with lower PFS and OS in mCRPC patients. We found a cut-off value of 0.22 providing the best discrimination for prognosis. CAR is a good prognosis biomarker, irrespective of the moment of evaluation and chosen treatment option.

Renal Transplantation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center 10-Year Experience.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease. The optimal timing of kidney transplantation for end-stage renal disease due to AAV and the risk of relapse after kidney are poorly defined. Our study aimed to evaluate the clinical outcomes of AAV after kidney transplantation, namely the risk of relapse, rejection, and oncologic disease. METHODS: This retrospective study included all patients with AAV submitted to a kidney transplant between January 2011 and December 2020. RESULTS: Twenty-seven patients (20 males/7 females; mean age 47 years) received a kidney transplant for end-stage renal disease secondary to microscopic polyangiitis (n = 25) or granulomatosis with polyangiitis (n = 2). All patients were in clinical remission at the time of the kidney transplant, but 11 patients were ANCA-positive. A vasculitis relapse after kidney transplantation occurred in only 1 patient (3.7%). Rejection episodes, proven by allograft biopsy, were present in 3 patients (11.1%), with graft losses in 2 (66.7%). The median time until the graft was lost after the initial rejection diagnosis was 27 ± 8 months. Oncologic complications were present in 9 patients (33.3%). Five patients died (18.5%), and the main cause of death was cardiovascular disease (n = 3, 60.0%), followed by oncologic disease (n = 2, 40.0%). CONCLUSIONS: Kidney transplantation is a safe and effective option for treating end-stage renal disease secondary to AAV. Current immunosuppression regimens make relapses and rejection infrequent but place oncologic complications at a higher incidence.

Vascular closure devices in living-donor nephrectomy: a much-needed systematic review and meta-analysis focusing on safety.

OBJECTIVE: To assess the safety of vascular closure devices in living-donor nephrectomy (LDN), as staplers and non-transfixion techniques (polymer locking and metal clips) are the methods employed to secure the renal vessels during laparoscopic and robotic LDN, but the use of clips has come into question since the United States Food and Drug Administration and manufacturers issued a contraindication. METHODS: A systematic review and meta-analysis were conducted to assess the safety of vascular closure devices (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42022364349). The PubMed, Scopus, the Excerpta Medica dataBASE (EMBASE), and the Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) databases were searched in September 2022. For comparative and non-comparative studies, incidence estimates and odds ratios (ORs), respectively, for the main variables regarding safety of vascular closure devices were pooled by using random effects meta-analyses. Quality assessment of the included comparative studies was conducted using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. RESULTS: Of the 863 articles obtained, data were retrieved from 44 studies, which included 42 902 patients. In non-comparative studies, the pooled estimate rates for device failure, severe haemorrhage rate, conversion to open surgery, and mortality were similar for both clips and staplers. Regarding the meta-analyses for comparative studies (three studies), there were no significant differences between the two groups for the severe haemorrhage rate (OR 0.57, 95% confidence interval [CI] 0.18-1.75; P = 0.33), conversion to open surgery (OR 0.35, 95% CI 0.08-1.54; P = 0.16), or death rate (OR 3.64, 95% CI 0.47-28.45; P = 0.22). Based on weak evidence, device failure was lower in the polymer clip group (OR 0.41, 95% CI 0.23-0.75; P = 0.00). CONCLUSIONS: This study has confirmed that there is no evidence for the superiority of any vascular closure device in terms of safety in LDN. Standardised recommendations for vascular control in this context should be carefully designed and prospectively evaluated.

Predicting bladder cancer risk in patients with hematuria. A single-centre retrospective study.

INTRODUCTION: The presence of blood in the urine should be promptly investigated to rule out urological malignancies, bladder cancer being the most frequent. Given its frequency among general population and the lack of unlimited health resources in an era of cost-effectiveness, it is important to prioritize patients with higher risk of malignancy. OBJECTIVES: To identify predictive factors of bladder cancer among patients presenting with hematuria. PATIENTS AND METHODS: We retrospectively reviewed 296 cases referred to our department for hematuria. We evaluated different demographic, clinical and ultrasound features to uncover possible associations with diagnosis of bladder cancer in those patients, to estimate the individual risk of being diagnosed with bladder cancer during the investigation of hematuria. RESULTS: A total of 296 patients were studied for hematuria between January 1, 2017 and December 31, 2019, 23.6% of those having ultimately bladder cancer confirmed after transurethral resection. Older age, male gender (OR 2.727, p = 0.069), a history of smoking (OR 3.84, p < 0.05), recurrent hematuria (OR 3.396, p < 0.05) and positive ultrasound exam for bladder cancer (OR 30.423, p < 0.05) were identified as predictors of bladder cancer in patients with hematuria. CONCLUSIONS: This study suggests that it is possible to reliably estimate the risk of bladder cancer in patients with hematuria, using clinical and imaging data to help defining who should be investigated first and in whom the investigation could be postponed.

Evaluation of the Effectiveness of Interventions on Nephrolithiasis in Transplanted Kidney.

CONTEXT: De Novo nephrolithiasis in renal transplant can have severe consequences since renal transplantation involves a single functioning kidney with medical and anatomical specificities (heterotopic transplantation on iliac vessels, immunosuppressive treatments, and comorbidities). OBJECTIVE: To systematically review all available evidence on the prevalence of de novo nephrolithiasis in renal transplant, presentation, and stone characteristics, and to report in a meta-analysis the efficacy of stone treatments (extracorporeal shock wave lithotripsy [ESWL], medical treatment, percutaneous nephrolithotomy [PCNL], open surgery, and ureteroscopy). EVIDENCE ACQUISITION: Medline, Embase, and the Cochrane Library were searched up to November 2021 for all relevant publications reporting the management of de novo nephrolithiasis in renal allografts. The primary outcome was stone-free rate (SFR) at 3 mo. Secondary outcomes included prevalence, stone characteristics (size, density, and composition), symptoms on presentation, need for drainage, complications, and recurrence. Data were narratively synthesized in light of methodological and clinical heterogeneity, and a meta-analysis was performed for SFR. The risk of bias of each included study was assessed. EVIDENCE SYNTHESIS: We included 37 retrospective studies with 553 patients and 612 procedures; of the 612 procedures 20 were antegrade ureteroscopy, 154 retrograde ureteroscopy, 118 PCNL, 25 open surgery, 155 ESWL, and 140 surveillance/medical treatment. The prevalence of nephrolithiasis in renal transplant was 1.0%. The mean stone size on diagnosis was 11 mm (2-50). The overall SFR at 3 mo was 82%: 96% with open surgery, 95% with antegrade ureteroscopy, 86% with PCNL, 81% with retrograde ureteroscopy, and 75% with ESWL. CONCLUSIONS: De novo nephrolithiasis in renal transplant is an infrequent condition. A high SFR were obtained with an antegrade approach (ureteroscopy, PCNL, and open approach) that should be considered in renal transplant patients owing to the heterotopic position of the renal graft. The choice of technique was correlated with stone size: generally ureteroscopy and ESWL for stones 11-12 mm (mean stone size) versus PCNL and open surgery for 17-25 mm stones. PATIENT SUMMARY: De novo nephrolithiasis in renal transplants is an infrequent situation that can have severe consequences on the function of the renal graft. We evaluated the efficacy of each treatment and noted that antegrade approaches (open surgery, percutaneous nephrolithotomy, and antegrade ureteroscopy) were associated with the highest stone-free rate. As opposed to the management of nephrolithiasis in native kidney, an antegrade approach should be considered more in renal transplant patients.

Anti-Algics in the Therapeutic Response of Breast and Urological Cancers.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

National consensus survey on management approaches for upper urinary tract obstruction: A comparative analysis of retrograde ureteric stent and percutaneous nephrostomy.

To the Editor, Upper urinary tract obstruction (UUTO) is a common scenario in clinical practice, and it is caused by a variety of diseases. Lithiasis, tumours and strictures are some of the principal aetiologies. Multiple factors may influence both the need for decompression of the obstructed collecting system and the urgency of procedure...

Are Pretransplant Kidney Biopsies Safe?

BACKGROUND: Annually, about 500 kidneys are transplanted in Portugal. Despite some studies looking into the procurement biopsies' benefits (like the potential of predicting long term results and establishing a baseline), few have studied its risks, especially in the period between the harvest and the transplant. METHODS: A cross-sectional study, including all patients who received a kidney graft between the 2019 and 2020 at the University Hospital of Coimbra (n = 203). Biopsies were done using a polar double core puncture technique with 18-gauge needles. RESULTS: Fifty-six patients (27.6%) received a biopsied graft. The median postoperative hemoglobin fall was 2.8 g/dL; this fall was more pronounced in the group that received a biopsied kidney (3.2 g/dL vs 2.6 g/dL; P < .05). The number of transfusions needed during the hospital stay (2.2 U vs 1.3 U; P < .05) and the median length of stay (13.2 ± 8.4 vs 10.6 ± 5.8, P < .05) were greater in the biopsied group. Patients who received a biopsied kidney were older (median age of 57.3 vs 46.9). Cold ischemia time was greater in the biopsied group (19 hours vs 15.2 hours; P < .05). However, we did not find a relation between the age and the hemoglobin drop or blood transfusions. At discharge, renal function was not statistically different between the 2 groups (P was nonsignificant). CONCLUSIONS: Despite the biopsies' potential advantages, they are not without risks. This study showed a statistical association between harvest biopsies and higher risks of hemorrhage, regardless of age. When needed, procurement biopsies seemed safe for the recipients, but at the expense of increased patient surveillance and resource consumption.

Nonmetastatic Castration-Resistant Prostate Cancer: Current Challenges and Trends.

Prostate carcinoma is a highly prevalent biologically and clinically diverse disease, generally associated with a consistent elevation of prostate-specific antigen levels. Castration-resistant prostate cancer represents a heterogeneous clinical setting that ranges from patients with an asymptomatic prostate-specific antigen elevation after hormone blockade failure and good performance status to patients with significant debilitating symptoms and rapidly progressive disease, leading to death. Nonmetastatic castration-resistant prostate cancer is a transient disease stage defined over specific criteria established within a sensitive time period. The majority of the patients with nonmetastatic castration-resistant prostate cancer will eventually develop metastatic lesions, associated with prostate cancer-specific morbidity and mortality. However, progression to metastatic disease is a heterogeneous process still not fully understood, with studies suggesting that younger age, high Gleason score (> 7), high prostate-specific antigen levels, reduced prostate-specific antigen doubling time (< 6 months), and a rapid alkaline phosphatase rise as potentially associated factors. Although the nonmetastatic castration-resistant prostate cancer treatment landscape has substantially evolved in recent years, the disease heterogeneity makes treatment decisions for this population challenging in the effort to achieve a balance between the risk of disease progression and the toxicity of new treatments in patients who often have associated comorbidities, yet are generally asymptomatic. The present article addresses the current main challenges in nonmetastatic castration-resistant prostate cancer management, including in diagnosis, owing to the development of new imaging modalities with a direct impact in disease detection, prognostic classification, as a result of the traditionally oversimplified definition of disease aggressiveness (mainly based on prostate-specific antigen doubling time), and patient selection for the most adequate treatment.

Kidney Retransplantation Outcomes: A Paired Recipient Control Study.

BACKGROUND: Despite progressive improvements in graft and patient survival after kidney transplantation over the last decades, an increasing number of patients are waitlisted for retransplantation. Identifying the risk factors for second graft failure can help us improve management for such patients. The aim of this study was to compare the outcomes of kidney retransplantation with those of first transplantation. METHODS: This retrospective study included all the recipients of a second kidney transplant between January 2008 and December 2019. For each patient with a second kidney transplant, we selected the paired recipient from the same donor. We excluded recipients of donations from living donors, patient-and-donor pairs with more than 1 transplant, and patients without a pair. The follow-up took place December 31, 2020. We included 152 patients, corresponding to 76 pairs of recipients. RESULTS: Patients who underwent a second transplant had significantly higher panel reactive antibody values and longer waiting time for retransplantation. Biopsy-proven acute rejection episodes were doubled in patients undergoing a second transplant (P = .12). There was a lower survival of second grafts at the first, fifth, and 10th year (P < .05). The main factor influencing graft loss for both groups was acute rejection, and, in patients, with a second transplant, acute rejection increased the risk of graft loss by 17 times (odds ratio, 17.5; 95% confidence interval, 4.19-98). CONCLUSIONS: The clinical results of second kidney transplants still fall short of first transplants, with the main factor of poor prognosis being acute rejection. In young patients, allocation and immunosuppression management should consider this risk to improve long-term outcomes.