Local recurrence of renal cell carcinoma after partial nephrectomy: applicability of the apparent diffusion coefficient of MRI as an imaging marker - a multicentre study.

Purpose: The goal of the study was an assessment of the diagnostic performance of diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) of magnetic resonance imaging (MRI) in distinguishing local recurrence (LR) of renal cell carcinoma (RCC) from benign conditions after partial nephrectomy. Material and methods: Thirty-nine patients after partial nephrectomy for solid RCC were enrolled in the study. Patients were followed up using MRI, which included DWI sequence (b = 800 s/mm2). All patients with MRI features of LR were included in the main group (n = 14) and patients without such features - into the group of comparison (n = 25). Apparent diffusion coefficient (ADC) values of suspicious lesions were recorded. In all patients with signs of locally recurrent RCC, surgical treatment was performed followed by pathologic analysis. Results: The mean ADC values of recurrent RCC demonstrated significantly higher numbers compared to benign fibrous tissues and were 1.64 ± 0.15 × 10-3 mm2/s vs. 1.02 ± 0.26 × 10-3 mm2/s (p < 0.001). The mean ADC values of RCCs' LR and benign post-op changes in renal scar substantially differed from mean ADC values of healthy kidneys' parenchyma; the latter was 2.58 ± 0.05 × 10-3 mm2/s (p < 0.001). In ROC analysis, the use of ADC with a threshold value of 1.28 × 10-3 mm2/s allowed us to differentiate local recurrence of RCC from benign postoperative changes with 100% sensitivity, 80% specificity, and accuracy: AUC = 0.980 (p < 0.001). Conclusions: The apparent diffusion coefficient of DWI of MRI can be used as a potential imaging marker for the diagnosis of local recurrence of RCC.

Urobiome in Gender-Related Diversities of Bladder Cancer.

Bladder cancer (BC) remains the most common malignancy of urinary tract. Sex-related differences in BC epidemiology, diagnosis, therapy, and outcomes have been reported. Throughout the recent years, extensive research has been devoted to genetic and molecular alterations in BC. Apart from the molecular background, another related concept which has been speculated to contribute to gender diversities in BC is the role of urinary pathogens in bladder carcinogenesis. Microbiome studies, fueled by the availability of high-throughput DNA-based techniques, have shown that perturbation in the microbiome is associated with various human diseases. The aim of this review is to comprehensively analyze the current literature according to sex-related differences in the microbiome composition in BC.

Patterns of care in patients with muscle-invasive bladder cancer - a retrospective cohort study.

A potential reason for poor survival among patients with muscle-invasive bladder cancer (MIBC) in Poland is initial disqualification from curative treatment due to advanced stage of the disease or low performance status. The aim of this study was to describe patterns of care in patients with newly diagnosed MIBC. This is a multicentre retrospective cohort study involving 296 consecutive patients with primary histologically diagnosed MIBC. Therapeutic decisions and potentially underlying clinical factors were analysed. Full clinical data was available for 285 patients. One hundred and sixty-four (57.5%) patients were qualified for radical cystectomy (RC), 32 (11.2%) patients for a second step of transurethral resection of the bladder tumour (TURBT) intentionally followed by systemic chemotherapy, four (1.4%) patients after complete TURBT were qualified for adjuvant intravesical chemotherapy only, while the remaining 85 (29.8%) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care. Patients disqualified from curative treatment were older (78 vs. 69 years, p < 0.02), had lower BMI values (24.5 vs. 25.7 kg/m(2), p < 0.02), lower haemoglobin concentration (11.6 vs. 12.9 mg/l, p < 0.02), declared lower rate of nicotine abuse (50.5% vs. 72.1%, p < 0.02), and had a shorter time interval between first symptom and diagnosis (30 vs. 60 days, p = 0.02). As the majority of Polish patients with primary MIBC receive curative treatment, the stage of the disease alone seems not to be the leading cause of poor survival. However, appropriateness of qualification for RC and treatment quality needs to be assessed for final conclusion on the factors influencing outcomes of treatment in Poland.

The presence of prostate cancer at biopsy is predicted by a number of genetic variants.

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low-risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.

Is urethral stricture really so often idiopathic? Exploring the etiology of urethral strictures in males undergoing urethroplasty: a multicenter retrospective cohort study.

Introduction: The aim of this study was to retrospectively evaluate the etiology of urethral stricture disease (USD) in a large series of patients undergoing urethroplasty. Material and methods: The multicenter retrospective cohort study was conducted at two reconstructive urology referral centers in years 2015-2022. Prior to the surgical intervention, all patients underwent diagnostic procedures including retrograde urethrography and voiding cystourethrography. We collected comprehensive demographic and medical data including the length and location of the stricture. We paid particular attention to identifying the underlying causes of USD in the medical records. Results: The study included 949 patients meeting criteria, with a mean age of 53. The primary cause of USD was identified as iatrogenic (404 cases, 42.6%), followed by trauma (210, 22.1%), previous hypospadias repair (122, 12.9%), lichen sclerosus (32, 3.4%), and infections (12, 1.3%). Notably, 169 patients (17.8%) did not have a discernible cause for their USD and were thus classified as idiopathic. Furthermore, it was observed that 66% of idiopathic USD cases were localized in the bulbar urethra. The etiology of USD varied significantly based on its localization (p <0.01). The mean stricture length differed among different causes, with the longest in patients with USD due to lichen sclerosus (41 mm), followed by previous hypospadias repair (35 mm), and iatrogenic causes (29 mm), p <0.001. Conclusions: Careful medical history-taking can identify the etiology of urethral stricture in over 80% of patients undergoing urethroplasty. The etiology of the USD impacts its location and length and thus can affect surgical treatment strategy and outcomes.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland.

BACKGROUND: The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20-fold). The geographical and ethnic extent of this recurrent allele has not yet been determined. METHODS: We assayed for the presence of the G84E mutation in 3,515 prostate cancer patients and 2,604 controls from Poland and estimated the odds ratio for prostate cancer associated with the allele. RESULTS: The G84E mutation was detected in 3 of 2,604 (0.1%) individuals from the general population in Poland and in 20 of 3,515 (0.6%) men with prostate cancer (Odds ratio [OR] = 5.0; 95% CI: 1.5-16.7; P = 0.008). The allele was present in 4 of 416 (1.0%) men with familial prostate cancer (OR = 8.4, 95% CI: 1.9-37.7; P = 0.005). CONCLUSIONS: The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases. We expect that the G84E founder mutation might be present in other Slavic populations.

A Systematic Review on Postoperative Antibiotic Prophylaxis after Pediatric and Adult Male Urethral Reconstruction.

In the era of antibiotic overuse and increasing antibiotic resistance, there is a gap in evidence regarding antibiotic stewardship, and in particular, perioperative antibiotic prophylaxis after urethral reconstruction. The aim of this systematic review was to evaluate the effectiveness and relevance of postoperative antibiotic prophylaxis after male pediatric and adult urethral reconstruction. An online search of MEDLINE database via PubMed was performed. The systematic review was registered in PROSPERO (CRD42022348555) and was conducted according to the PRISMA guidelines and AMSTAR 2 checklist. A narrative synthesis of included studies was performed. After the screening of 1176 publications, six studies regarding antibiotic prophylaxis after hypospadias reconstruction and two studies regarding antibiotic prophylaxis after urethroplasty in adults were eligible to be included in the systematic review. All but one of the studies on hypospadias repair showed no benefit from postoperative antibiotic prophylaxis. The level of evidence on postoperative antibiotic prophylaxis after urethroplasty in adults is low. Neither of the two studies included in the review showed a benefit from antibiotic use. Postoperative prophylaxis after hypospadias repair is not effective in preventing urinary tract infections and wound infections. It seems that the use of postoperative prophylaxis after urethroplasty in adults is also not beneficial, but there is a high need for high-quality scientific data.

Sex Remains Negative Prognostic Factor in Contemporary Cohort of High-Risk Non-Muscle-Invasive Bladder Cancer.

Sex-specific differences in outcomes of patients diagnosed with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have been reported with controversial findings. This study aims to investigate sex-specific diversities in the treatment and oncologic outcomes of primary HR-NMIBC in a multicenter setting. A multicenter retrospective analysis of 519 patients (388 men and 131 women) treated with transurethral resection (TUR) for primary HR-NMIBC was performed. Univariable and multivariable Cox regression models were used to investigate the association of clinico-pathologic features and generate hazard ratios (HRs). Second-look TUR (reTUR) was performed in 406 (78%) patients. A total of 218 (42%) of patients were subjected to an induction course of intravesical BCG (Bacillus Calmette−Guérin) plus maintenance therapy. The median follow-up was 44 months. Among the entire cohort, 238 (46%) and 86 patients (17%) had recurred and progressed to muscle-invasive disease (MIBC), respectively. Female sex was associated with increased risk of disease recurrence in the entire cohort: HR = 1.94, 95% CI = 1.48−2.55, p < 0.001 and HR = 1.91, 95% CI = 1.39−2.60, p < 0.001 in univariate and multivariate analysis, respectively. In patients subjected to reTUR and treated additionally with BCG, female sex was associated with increased risk of disease recurrence in univariate analysis (HR 1.81, 95% CI 1.07−3.06, p = 0.03), but not in multivariate analysis (HR 1.99, 95% CI 0.98−4.02, p = 0.06). There was no difference between sexes with regard to disease progression. HR-NMIBC diagnosed in females is associated with higher risk of disease recurrence when compared to males.

Systemic treatment of the metastatic renal cell carcinoma: usefulness of the apparent diffusion coefficient of diffusion-weighted MRI in prediction of early therapeutic response.

Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration-7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05-11.61), 7.40 ± 2.50 months (95% CI = 5.61-9.19) and 4.20 ± 1.99 months (95% CI = 2.78-5.62) accordingly (p < 0.05). There was no difference in change of main lesions' longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35-25.87) and by 7.66 ± 6.72% (95% CI = 2.86-12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.

Review on gender differences in non-muscle invasive bladder cancer.

Differences in the epidemiology, diagnosis and outcomes according to gender in patients diagnosed with non-muscle invasive bladder cancer (NMIBC) has been widely reported. In this article we present gender-specific differences in NMIBC in terms of epidemiology, risk factors, first clinical presentation, management and clinical outcomes based on systematically review evidence of existing literature. A literature search of English-language publications that included an analysis of the association of gender differences in patients with NMIBC was performed using PubMed. Sixty-four studies were selected for analysis with consensus of all authors. The incidence and mortality for urothelial bladder cancer (UBC) are higher in men, whereas cancer specific mortality to incidence ratio is significantly lower for men than for women. This phenomenon could be partially explained by differences in exposure to bladder cancer carcinogens. However female gender is associated with higher stage at presentation. Thirteen studies with a total of 11,069 patients diagnosed with NMIBC were included for analysis according to outcomes. In studies that found statistically significant differences in outcomes between sexes, female gender was reported as risk factor for disease recurrence, progression or cancer specific mortality. None of included studies found worse outcomes in men when compared to women with NMIBC. Results of our review suggest that female gender in patients diagnosed with NMIBC is associated-though inconsistently-with higher stage at presentation and poorer outcomes. Numerous factors may influence gender gap in incidence rate, clinical management and reported outcomes. Consensus on comparable data collection in routine practice and prospective trials including clinical outcomes are required to identify gender-specific differences in patients diagnosed with NMIBC.

Potential clinical applications of microRNAs as biomarkers for renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for 3% of adult malignancies and more than 90% of kidney neoplasms. High rates of undiagnostic percutaneous kidney biopsies and difficulties in reliable pre-operative differentiation between malignant and benign renal tumors using contemporary imaging techniques result in large numbers of redundant surgeries. Absence of specific biomarkers for early detection and monitoring complicates on-time diagnosis of the disease and relapse. For the patients followed up after having a nephrectomy, a noninvasive and sensitive biomarker enabling early detection of disease relapse would be extremely useful. MATERIAL AND METHODS: The study is a review of recent knowledge regarding potential clinical applications of microRNAs (miRNAs) as biomarkers of RCC. RESULTS: MicroRNAs are essential regulators of various processes such as cell proliferation, differentiation, development and death; they have been implicated in diverse biological and pathological processes in RCC. There is a class of miRNAs that promote RCC development (oncomirs) and a class of miRNAs that negatively regulate oncogenes, suppress tumor growth and invasion, and thus could be considered treatment agents (anti-oncomirs). Separate miRNAs and specific miRNAs expression profiles have been identified, enabling early detection of the disease, prediction of response to systemic therapy, or prognostication of biological behavior of the disease. CONCLUSIONS: The miRNA network analysis and gene profiling may help to identify the most sensible molecular signatures of RCC that can be used for diagnostic purposes, as well as poor prognosis signatures and poor therapeutic response signatures in patients who undergo systemic therapy.

Should all specimens taken during surgical treatment of patients with benign prostatic hyperplasia be assessed by a pathologist?

INTRODUCTION: In some patients submitted to transurethral resection of the prostatic (TURP) or prostatectomy (OAE) due to benign prostate hyperplasia (BPH), pathological evaluations (PE) revealed coexistence of prostate cancer (PCa) and BPH. The aim of the study is to evaluate the incidence of PCa diagnosed incidentally in prostate specimens taken during BPH surgery, to assess the need of routine PE and to define the group of patients in whom PE could be abandoned without the risk of omitting clinically significant PCa. MATERIAL AND METHODS: 968 consecutive men were subjected to surgical treatment due to BPH in Jan. 2004-Sep. 2010. RESULTS: 823 (85%) underwent TURP and 145 (15%) OAE. Incidental (Inc) PCa was diagnosed in 34(3.5%) pts. T1a and T1b stages were determined in 19 (2%) and 15 (1.5%) cases. Preoperative prostate biopsy due to abnormal prostate specific antigen (PSA) or digital rectal exam (DRE) was performed in 85 (8.8%) pts. Of PCa pts, 7 (20.58%) had undergone a cancer negative biopsy preoperatively. In BPH pts, 78 (8.35%) had undergone a prostate biopsy previously (p <0.01). Univariate and logit regression analyses had not revealed any correlations between age, Pv, serum PSA and frequency of IncPCa. The difference in rate of PCa diagnosed in patients with PSAD ≥0.15 and <0.15 was 8 pts (14.04%) and 20 pts (4.05%), respectively (p <0.001). Gls in those pts was >6 only in 4 cases. CONCLUSIONS: Despite the fact of low PCa detection rate observed in our study, this condition was clinically relevant in 15 (1.5%) subjects. It is difficult to establish any cut off values of pts' age, Pv, serum PSA level suggestive of negligible risk for prostate cancer.

Clinical value of extended pelvic lymph node dissection in patients subjected to radical prostatectomy.

INTRODUCTION: Extended pelvic lymph node dissection (ePLND) is advised to complement radical prostatectomy (RP) in intermediate and high risk prostate cancer patients. AIM: To assess the risk of nodal involvement in patients subjected to laparoscopic radical prostatectomy and to characterize the group of patients with lymph node (LN) metastases. MATERIAL AND METHODS: Data of patients subjected to laparoscopic radical prostatectomy with ePLND between February 2011 and June 2013 were analyzed. The LN that were removed included presacral nodes, common, external and internal iliac nodes and obturator ones. RESULTS: Mean number of removed LNs was 19. Metastases within LN were found in 13 (16.6%) patients. In comparison to those without LN involvement, patients who were found to have LN metastases had a greater number of positive biopsy cores (3.7 vs. 5.3, p < 0.01), maximum percentage of cancer in biopsy core (47.0 vs. 67.6, p < 0.01), greater biopsy and specimen Gleason scores (7.0 vs. 7.7 and 7.0 vs. 7.8) and more frequently advanced clinical and pathological stage. The most frequent landing sites of prostate cancer were obturator and presacral nodes (100% and 38%). Eleven patients (85%) among those with positive LN had locally advanced disease. CONCLUSIONS: The risk of LN metastases in intermediate and high risk prostate cancer patients is significant. Therefore, if radical prostatectomy is chosen, ePLND should be performed. The majority of patients with involvement of pelvic LN have locally advanced disease which would refer them to adjuvant radiation if managed without nodal dissection.

Should active surveillance in prostate cancer patients be based on a single histological assessment?

INTRODUCTION: Active surveillance (AS) is always associated with a degree of uncertainty, whether or not prostate biopsy (TRUSBx) results indeed can be relied on for evaluation of cancer stage and histological grade, as the most commonly observed limitations of TRUSBx are undergrading, understaging and underestimating true prostate cancer (PCa) volume. We evaluated prostate cancer characteristics in men who could have been offered active surveillance based on clinical features and TRUSBx results, and compared them with the same patient's histology results following their radical prostatectomy (RP). Moreover, we assessed the level of consistency in reporting TRUSBx and RP specimens by the same pathologist on two separate occasions, as well as by another independent pathologist. MATERIAL AND METHODS: All patients who underwent RP between 2005 and 2008 had their medical records reviewed retrospectively. All histological specimens were prospectively re-evaluated by the same pathologist, as well as by a second to assess for intra- and interobserver variability, respectively. RESULTS: Eight out of a total of 124 patients who underwent RP could have been offered AS on the basis of initial microscopic reports. However, there was significant intra- and interobserver variability. The differences in the histological grade of the specimens obtained from TRUSBx and RP, reported by the same pathologist and by the second pathologist were apparent in 6 and 4 cases, and in 7 and 6 patients, respectively. CONCLUSIONS: We recommend that the decision about AS should be made after at least two pathologists have jointly reviewed and agreed on the TRUSBx histology results.

A common nonsense mutation of the BLM gene and prostate cancer risk and survival.

BACKGROUND: Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet. METHODS: To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls. RESULTS: Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases. CONCLUSIONS: BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland.

Clinical significance of surgical margin status in patients subjected to radical prostatectomy.

The aim of this study is to evaluate the clinical value of positive surgical margins (PSM) in patients subjected to radical prostatectomy (RP). The data of men who were subjected to RP from the 1st of January, 2001 to the 30th of May, 2010 were analyzed. Specimens with PSM were again evaluated to confirm the presence of positive margins. PSM were found in 64 (25%) out of 255 analyzed patients. Out of all clinical features, only biopsy Gleason score and clinical stage of the disease were found to be predictive of PSM. Biochemical recurrence (BR) was found in 42 (16.5%) men, among them 17 (26.6%) had PSM and 25 (13.1%) had negative margins. The risk of BR in those with "focal" PSM (<3 mm) did not differ from the risk of BR observed in patients without PSM. In contrast, the likelihood of BR was significantly greater in cases of PSM in which maximum longitude exceeded 3 mm. Reevaluation of the PSM specimens revealed equivocal margins status in six cases. PSM are not inevitably associated with BR. The risk of failure is influenced by their length. Reevaluation of the prostate specimen may lead to surgical margins status modification.