Genetic aberrations of homologous recombination repair pathways in prostate cancer: The prognostic and therapeutic implications.

Prostate cancer (PC) is the second most common cancer in men worldwide. Homologous recombination repair (HRR) gene defects have been identified in a significant proportion of metastatic castration-resistant PC (mCRPC) and are associated with an increased risk of PC and more aggressive PC. Importantly, it has been well-documented that poly ADP-ribose polymerase (PARP) inhibition in cells with HR deficiency (HRD) can cause cell death. This has been exploited for the targeted treatment of PC patients with HRD by PARP inhibitors. Moreover, it has been shown that platinum-based chemotherapy is more effective in mCRPC patients with HRR gene alterations. This review highlights the prognosis and therapeutic implications of HRR gene alterations in PC.

Guillain-Barré Syndrome following intravesical Bacillus Calmette-Guérin therapy for bladder cancer: a rare and intriguing case report.

Intravesical Bacillus Calmette-Guérin (BCG) therapy is a standard treatment for non-muscle invasive bladder cancer, but some patients experience side effects that lead to treatment discontinuation. Local side effects are typically mild, while systemic side effects can be severe and life-threatening. BCG therapy has immunotherapy effects on bladder cancer, but the mechanism is not fully understood. Due to its effect on the immune system, patients may also develop rare autoimmune complications, such as neuropathy. This case report suggests a potential association between BCG therapy and Guillain-Barré Syndrome (GBS), as a patient developed GBS after receiving intravesical BCG therapy for invasive bladder cancer.

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis.

Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. Methods: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. Results: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p < 0.00001; RR = 1.91), rash incidence was equal to 11.1% (160/1441) vs. 6.5% (86/1320) (Z = 4.35; p <0.0001; RR = 1.75), pruritis was 13.6% (201/1473) vs. 7.7% (104/1352) (Z = 5.35; p < 0.00001; RR = 1.83), fever was 10.5% (42/399) vs. 6.6% (22/330) (Z = 2.27; p = 0.02; RR = 1.77), discontinuation rate was 18% (91/504) vs. 3% (36/434) (Z = 4.78; p < 0.00001; RR = 2.41), and death rate was 2.6% (13/504) vs. 0.7% (3/434) (Z = 1.90; p = 0.06; RR = 2.77). Conclusions: It was observed that the combined (durvalumab and tremelimumab) vs. monotherapy (durvalumab) is associated with a higher risk of treatment discontinuation, mortality, fever, diarrhea, rash, pruritis, and reduced appetite. This information is relevant and should be disclosed, especially to patients that are currently enrolled in clinical trials considering this combined therapy.

A rare case of renal artery aneurysm - dawning of new treatment approach.

Renal artery aneurysms are a rare occurrence, with a prevalence of about <1%. The majority of patients are asymptomatic and are diagnosed through incidental findings on imaging. In very rare occurrences, the aneurysm can rupture and cause significant morbidity and even death.

Impact of Preoperative Stenting on the Outcome of Flexible Ureterorenoscopy for Upper Urinary Tract Urolithiasis: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to investigate the effect of preoperative stenting (POS) on the perioperative outcomes of flexible ureterorenoscopy (fURS). MATERIALS AND METHODS: A systematic review and meta-analysis was conducted based on the PRISMA statement. From the initially retrieved 609 reports, we excluded the ineligible studies at 2 stages. We only included studies that contained fURS patients with and without POS in the same report. Data of patients who underwent semirigid ureteroscope only were excluded from the analysis. The Newcastle-Ottawa Scale (NOS) system was applied for risk of bias assessment. RESULTS: A total of 20 studies including 5,852 patients were involved. 48.5% of the patients had preoperative stent. Stone-free rate was significantly higher with prestenting; odds ratio (OR) was 1.98 (95% CI: 1.51-2.58) (Z = 5.02; p = 0.00001). It also displayed tendency toward lower complications; OR was 0.74 (95% CI: 0.52-1.05) (Z = 1.67; p = 0.09). POS significantly increased the use of ureteral access sheath; OR was 1.49 (95% CI: 1.05-2.13) (Z = 2.22; p = 0.03). Risk of bias assessment showed 13 and 7 studies with low and moderate risk, respectively. CONCLUSIONS: POS clearly improves the stone-free rates after fURS. It might reduce the complications, especially ureteral injury. These findings might help solve the current debate and can be useful for urologists during patient counselling for a proper decision-making.

Impact of Prostate Size on the Outcomes of Radical Prostatectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: The impact of prostate size on the radical prostatectomy outcome is not clear. Several published reports have shown conflicting results. OBJECTIVES: To investigate the effect of prostate size on the surgical, functional and oncological results of radical prostatectomy. METHODS: A systematic review and meta-analysis were carried out in accordance with the PRISMA criteria. Finally, we investigated the research that reported on the impact of prostate size on radical prostatectomy outcome. The Review Manager (RevMan) software version 5.4 was utilized for statistical analysis. RESULTS: Eighteen studies including 12,242 patients were included. Estimated blood loss was significantly less with smaller prostates (Z = 3.01; p = 0.003). The complications rate was 17% with larger prostates, compared to 10% for smaller prostates (Z = 5.73; p < 0.00001). Seventy-three percent of patients with a smaller prostate were continent within one month, compared to 64% with a larger prostate (Z = 1.59; p = 0.11). The rate of positive surgical margins was significantly higher with smaller prostates (20.2% vs. 17.8%). (Z = 2.52; p = 0.01). The incidence of biochemical recurrence was higher with smaller prostates (7.8% vs. 4.9%) (Z = 1.87; p = 0.06). CONCLUSION: Larger prostate size is associated with more blood loss and a higher rate of complications. However, the oncological outcome is better, compared to that in patients with smaller prostates. The impact of the size on the functional outcome is not clear.

Single-Port versus Multiple-Port Robot-Assisted Radical Prostatectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Single-port robotic-assisted radical prostatectomy has been reported as a safe and feasible technique. However, recent studies comparing single-port versus multiple-port robotic radical prostatectomy have displayed conflicting results. OBJECTIVES: To investigate the benefit of single-port robotic radical prostatectomy and the impact on outcome compared to multiple-port robotic radical prostatectomy. METHODS: Based on PRISMA and AMSTAR criteria, a systematic review and meta-analysis were carried out. Finally, we considered the controlled studies with two cohorts (one cohort for single-port RARP and the other cohort for multiple-port RARP). For statistical analysis, Review Manager (RevMan) software version 5.4 was used. The Newcastle-Ottawa Scale was employed to assess the risk of bias. RESULTS: Five non-randomized controlled studies with 666 patients were included. Single-port robotic radical prostatectomy was associated with shorter hospital stays. Only 60.6% of single-port patients (109/180) required analgesia compared to 90% (224/249) of multiple-port patients (Z = 3.50; p = 0.0005; 95% CI 0.07:0.47). Opioid administration was also significantly lower in single-port patients, 26.2% (34/130) vs. 56.6% (77/136) (Z = 4.90; p < 0.00001; 95% CI 0.15:-0.44) There was no significant difference in operative time, blood loss, complication rate, positive surgical margin rate, or continence at day 90. CONCLUSION: The available data on single-port robotic radical prostatectomy is very limited. However, it seems comparable to the multiple-port platform in terms of short-term outcomes when performed with expert surgeons. Single-port prostatectomies might provide a shorter hospital stay and a lower requirement for opioids; however, randomized trials with long-term follow-up are mandatory for valid comparisons.

Linitis plastica of the rectum secondary to metastatic prostate cancer: A case report of a rare presentation and literature review.

Linitis plastica is a rare tumor with poor prognosis. It is a circumferentially infiltrating intramural tumor which can result in rigid, nondistensible thickening of the affected organ. It most commonly affects the stomach, followed by the rectum, and can be due to primary or secondary cancer. Secondary rectal linitis plastica (RLP) caused by metastatic cancers has been reported from the stomach, breast, gallbladder, urinary bladder, and very rarely, the prostate, with only <5 reported cases in the literature. We report the case of a 66-year-old man who presented with altered bowel habit and loss of weight, with elevated prostate-specific antigen of 180.6 ng/mL. Sigmoidoscopy showed thickened rectal mucosa, and biopsy was negative for malignancy. Magnetic resonance imaging showed circumferential wall thickening, "target sign" appearance suggestive of RLP, PIRADS 5 lesion with extraprostatic extension, infiltrating bilateral seminal vesicles, and right neurovascular bundle. Repeat colonoscopy was performed under anesthesia, and deeper biopsy revealed poorly differentiated metastatic prostate adenocarcinoma. This case report highlights the atypical presentation of metastatic prostate cancer secondary to RLP, the rarity of this condition, and emphasizes the importance of deeper biopsy in RLP due to disease involvement predominantly in the submucosa and muscularis propria layers.

Urethral recurrence after radical cystectomy for urothelial carcinoma: A systematic review and meta-analysis.

PURPOSE: Currently, identified factors for urethral recurrence (UR) are based on individual reporting which has displayed controversy. In addition, risk of UR is one of the limiting factors to offer neobladder diversion during radical cystectomy (RC). We aim to systematically evaluate the incidence and risk factors of UR post-RC and its effect on survival. MATERIALS AND METHODS: A systematic online search was conducted according to PRISMA statement for publications reporting on UR after RC. From initial 802 results, 14 articles including 6169 patients were included finally after exclusion of ineligible studies. RESULTS: The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no significant effect on UR. Men displayed tendency toward higher incidence of UR (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed tendency toward better disease specific survival, yet not significant (hazard ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the retrospective nature of the included studies. CONCLUSION: Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.

A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer.

OBJECTIVE: This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed. RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively. CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

The Role of Radical Prostatectomy and Radiotherapy in Treatment of Locally Advanced Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The role of radical prostatectomy (RP) is still controversial for locally advanced prostate cancer (PC). Radiotherapy (RT) and hormonal therapy (HT) are usually used as a primary treatment. MATERIAL AND METHODS: A systematic online search was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Eligible publications reporting the overall survival (OS) and/or disease-specific survival (DSS) were included. A total of 14 studies, including 17,869 patients, were considered for analysis. The impact of therapeutic modalities on survival was assessed, with a risk of bias assessment according to the Newcastle Ottawa Scale. RESULTS: For RP, RT, and HT, the mean 10-year OS was 70.7% (95% CI 61.3-80.2), 65.8% (95% CI 48.1-83.3), and 22.6% (95% CI 4.9-40.3; p = 0.001), respectively. The corresponding 10-year DSS was 84.1% (95% CI 75.1-93.2), 89.4% (95% CI 70.1-108.6), and 50.4% (95% CI 31.2-69.6; p = 0.0127), respectively. Among all treatment combinations, RP displayed significant improvement in OS when included in the treatment (Z = 4.01; p < 0.001). Adjuvant RT significantly improved DSS (Z = 2.7; p = 0.007). Combination of RT and HT favored better OS in comparison to monotherapy with RT or HT (Z = 3.61; p < 0.001). CONCLUSION: Improved outcomes in advanced PC were detected for RP plus adjuvant RT vs. RP alone and RT plus adjuvant HT vs. RT alone with comparable survival results between both regimens. RP with adjuvant RT may present the modality of choice when HT is contraindicated.

Total proximal ureter substitution using buccal mucosa.

The surgical treatment of a long proximal ureteral stricture is a challenging situation for reconstructive surgeons. Despite the underlying morbidities, ileal interposition and autotransplantation are the options available to treat complex cases of long segment ureteral stricture. Buccal mucosa has shown excellent results in urethroplasty. However, its use in ureteral reconstruction is infrequent. We report on a 64-year-old female patient with multiple comorbidities and prior abdominal surgeries for Crohn's disease who underwent a successful total substitution of a long segment of the proximal ureter using buccal mucosa. Regular postoperative isotope scans showed improvement in renal function. Based on the pleasant outcome of this case and review of the literature, buccal mucosa might be a viable option with low morbidity in selected cases.

Clinicopathological Features and Prognostic Value of Incidental Prostatic Adenocarcinoma in Radical Cystoprostatectomy Specimens: A Systematic Review and Meta-Analysis of 13,140 Patients.

PURPOSE: There is controversy in the literature about the oncologic significance of incidental prostate cancer detected at radical cystoprostatectomy for bladder cancer. MATERIALS AND METHODS: An online search was done for studies reporting incidental prostate cancer in cystoprostatectomy specimens. After following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines we identified a total of 34 reports containing 13,140 patients who underwent radical cystoprostatectomy for bladder cancer with no previous history of prostate cancer. A cumulative analysis was performed on the available data regarding prevalence, clinicopathological features and oncologic outcomes. RevMan, version 5.3 was used for data meta-analysis. RESULTS: Of the 13,140 patients incidental prostate cancer was detected in 3,335 (24.4%). Incidental prostate cancer was significantly associated with greater age (Z = 3.81, p = 0.0001, d = 0.27, 95% CI -0.14-0.68), lymphovascular invasion of bladder cancer (Z = 2.07, p = 0.04, r = 0.14, 95% CI 0.09-0.18) and lower 5-year overall survival (Z = 2.2, p = 0.03). Among patients with clinically significant and insignificant prostate cancer those with clinically significant prostate cancer significantly more frequently showed a positive finding on digital rectal examination (Z = 3.12, p = 0.002, r = 0.10, 95% CI 0-0.19) and lower 5-year overall survival (Z = 2.49, p = 0.01) whereas no effect of age was observed (p = 0.15). Of 1,320 patients monitored for biochemical recurrence prostate specific antigen recurrence, defined as prostate specific antigen greater than 0.02 ng/ml, developed in 25 (1.9%) at between 3 and 102 months. CONCLUSIONS: This meta-analysis suggests that incidental prostate cancer detected during histopathological examination of radical cystoprostatectomy specimens might be linked with adverse characteristics and outcomes in patients with invasive bladder cancer.

The current status of checkpoint inhibitors in metastatic bladder cancer.

For many decades, no significant improvements could be achieved to prolong the survival in metastatic bladder cancer. Recently, systemic immunotherapy with checkpoint inhibitors (anti-PD-L1/anti-CTLA-4) has been introduced as a novel treatment modality for patients with metastatic bladder cancer. We conducted a systematic review according to the PRISMA statement for data published on the clinical efficacy of checkpoint inhibitors in metastatic bladder cancer. Clinical efficacy of anti PD-L1 therapy was investigated in prospective trials in a total of 155 patients. Patients with positive expression for PD-L1 tended towards better overall response rates (ORR) compared to those with negative expression (34/76 vs 10/73, 45 vs 14 %; p = 0.21). Among patients with PD-L1 positive tumors, those with non-visceral metastases exhibited significantly higher ORR compared to those with visceral metastases (82 vs 28 %; p = 0.001). For anti-CTLA4 therapy, there were no data retrievable on clinical efficacy. Although data on clinical efficacy of checkpoint inhibitors in metastatic bladder cancer are currently limited, the efficacy of these drugs might depend mainly on the metastatic volume and immune system integrity. Patients with PD-L1 positive tumors and non-visceral metastases seem to derive the highest benefit from therapy.

Systemic anti-CTLA-4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism?

Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.

Algorithm for Optimal Urethral Coverage in Hypospadias and Fistula Repair: A Systematic Review.

CONTEXT: Although urethral covering during hypospadias repair minimizes the incidence of fistula, wide variation in results among surgeons has been reported. OBJECTIVE: To investigate what type of flap used during Snodgrass or fistula repair reduces the incidence of fistula occurrence. EVIDENCE ACQUISITION: We systematically reviewed published results for urethral covering during Snodgrass and fistula repair procedures. An initial online search detected 1740 reports. After exclusion of ineligible studies at two stages, we included all patients with clear data on the covering technique used (dartos fascia [DF] vs tunica vaginalis flap [TVF]) and the incidence of postoperative fistula. EVIDENCE SYNTHESIS: A total of 51 reports were identified involving 4550 patients, including 33 series on DF use, 11 series on TVF use, and seven retrospective comparative studies. For distal hypospadias, double-layer DF had the lowest rate of fistula incidence when compared to single-layer DF (5/855 [0.6%] vs 156/3077 [5.1%]; p=0.004) and TVF (5/244, 2.0%), while the incidence was highest for single-layer DF among proximal hypospadias cases (9/102, 8.8%). Among repeat cases, fistula incidence was significantly lower for TVF (3/47, 6.4%) than for DF (26/140, 18.6%; p=0.020). Among patients with fistula after primary repair, the incidence of recurrence was 12.2% (11/90) after DF and 5.1% (5/97) after TVF (p=0.39). The absence of a minimum follow-up time and the lack of information regarding skin complications and rates of urethral stricture are limitations of this study. CONCLUSION: A double DF during tubularized incised plate urethroplasty should be considered for all patients with distal hypospadias. In proximal, repeat, and fistula repair cases, TVF should be the first choice. On the basis of these findings, we propose an evidence-based algorithm for surgeons who are still in their learning phase or want to improve their results. PATIENT SUMMARY: We systematically reviewed the impact of urethral covering in reducing fistula formation after hypospadias repair. We propose an algorithm that might help to maximize success rates for tubularized incised plate urethroplasty.

Role of laparoscopy in ureteropelvic junction obstruction with concomitant pathology: a case series study.

INTRODUCTION: Laparoscopic pyeloplasty is considered a standard treatment for ureteropelvic junction obstruction (UPJO). However, the presence of another pathology makes it a more challenging operation and guides the surgeon towards open conversion. In this study, we present our experience in difficult pyeloplasty cases managed by laparoscopy. MATERIAL AND METHODS: Six patients (4 females and 2 males) with an average age of 44 and a range of 27 to 60 years old, were diagnosed for UPJO. Three were on the left side and 3 on the right side. In addition to UPJO, 2 patients had renal stones, one patient had both renal ptosis and an umbilical hernia, 3 patients had a para-pelvic cyst, hepatomegaly and malrotated kidney, respectively. All patients had a preoperative ultrasound, CT or IVU, and a renal isotope scan. Laparoscopic pyeloplasty was performed according to the dismembered Anderson-Hynes technique with auxiliary maneuver, according to the pathology. RESULTS: All patients were treated successfully for UPJO and the concomitant pathologies, except hepatomegaly and malrotation. Mean operative time was 125 minutes and estimated blood loss was <50 ml. CONCLUSIONS: Laparoscopic pyeloplasty can be performed in difficult situations provided that the surgeon has enough experience with laparoscopy.