The presence of cribriform pattern in prostate biopsy and radical prostatectomy is associated with negative postoperative pathological features.

Introduction: Prostate cancer is the second most common male cancer worldwide. Its rising incidence and high overtreatment rate drive the search for new prognostic factors. Histopathological variants, such as cribriform pattern (CP), are associated with poorer oncologic outcome. The aim of this study was to assess the correlation between CP in prostate biopsy and radical prostatectomy (RP) and postoperative pathological features. Material and methods: In this retrospective, single-centre study we analysed the reviewed medical records of 100 men who underwent minimally invasive RP in the years 2017-2019. RP histopathological examination was performed by a single expert pathologist, and preoperative biopsies were assessed by various professionals from different referral centres. Results: 48% of men underwent endoscopic RP with limited lymphadenectomy, whereas 52% underwent laparoscopic RP with extended lymphadenectomy. CP in biopsy was present in 6 patients: 3 in each of both groups (6.3% and 5.8%, respectively). Lymph node metastases were present in 50% and 10% of patients with and without CP in biopsy, respectively (p = 0.028). Postoperative histopathological examination revealed CP in 65%. CP in RP was associated with higher International Society of Urological Pathology (ISUP) (p < 0.001), extraprostatic extension (EPE) (p = 0.001), seminal vesicle invasion (SVI) (p = 0.001), and positive surgical margin (PSM) (p = 0.004). Thirteen (20%) of the patients with CP in the RP specimen had lymph node metastasis, and none of the patients without CP in the RP specimen had regional LN metastasis. Conclusions: The presence of CP in a biopsy specimen and RP is associated with negative postoperative features. Therefore, efforts should be made to increase CP reporting in biopsies because its identification could trigger a more radical surgical approach with extended lymphadenectomy.

Impact of Nutritional Status of Patients with Head and Neck Squamous Cell Carcinoma on the Expression Profile of Ghrelin, Irisin, and Titin.

The goal of this paper was the evaluation of the changes in the expression profile of irisin, ghrelin, and titin in the carcinoma tissue and in the blood of patients with head and neck squamous cell carcinoma (HNSCC), including determining the profile of their expression in relation to patient nutrition. The study included 56 patients with diagnosed squamous cell carcinoma of HNSCC in the T3 and T4 stages of the disease. Healthy control tissue specimens were collected from an area 10 mm outside the histologically negative margin. In turn, the blood and serum from the control group came from healthy volunteers treated for non-oncologic reasons (n = 70). The molecular analysis allowed us to determine the profile of irisin, ghrelin, and titin methylation, evaluate their expression on the level of mRNA (quantitative Reverse Transcription Polymerase Chain Reaction; qRT-PCR) and protein (Enzyme-Linked Immunosorbent Assay Reaction; ELISA) in the carcinoma tissue and the margin of healthy tissue, as well as in serum of patients in the study and control groups. At the start of our observations, a Body Mass Index (BMI) < 18.5 was noted in 42 of the patients, while six months after the treatment a BMI < 18.5 was noted in 29 patients. We also noted a decrease in the expression of irisin, ghrelin, and titin both on the level of mRNA and protein, as well as a potential regulation of their expression via DNA methylation. There is no convincing evidence that the proteins assayed in the present work are specific with regard to HNSSC.

Prostate Cancer Morphologies: Cribriform Pattern and Intraductal Carcinoma Relations to Adverse Pathological and Clinical Outcomes-Systematic Review and Meta-Analysis.

The present study aimed to assess the association between the cribriform pattern (CP)/intraductal carcinoma (IDC) and the adverse pathological and clinical outcomes in the radical prostatectomy (RP) cohort. A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA). The protocol from this review was registered on the PROSPERO platform. We searched PubMed®, the Cochrane Library and EM-BASE® up to the 30th of April 2022. The outcomes of interest were the extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node metastasis (LNS met), risk of biochemical recurrence (BCR), distant metastasis (MET) and disease-specific death (DSD). As a result, we identified 16 studies with 164 296 patients. A total of 13 studies containing 3254 RP patients were eligible for the meta-analysis. The CP/IDC was associated with adverse outcomes, including EPE (pooled OR = 2.55, 95%CI 1.23-5.26), SVI (pooled OR = 4.27, 95%CI 1.90-9.64), LNs met (pooled OR = 6.47, 95%CI 3.76-11.14), BCR (pooled OR = 5.09, 95%CI 2.23-11.62) and MET/DSD (pooled OR = 9.84, 95%CI 2.75-35.20, p < 0.001). In conclusion, the CP/IDC belong to highly malignant prostate cancer patterns which have a negative impact on both the pathological and clinical outcomes. The presence of the CP/IDC should be included in the surgical planning and postoperative treatment guidance.

Not as black as it is painted? The impact of the first wave of COVID-19 pandemic on surgical treatment of urological cancer patients in Poland - a cross-country experience.

Introduction: In the majority of Western European countries, the coronavirus disease (COVID-19) pandemic has led to a dramatic reduction in urooncological surgeries. Our objective was to evaluate the impact of the pandemic on volume and patterns of urooncological surgery in Poland. Material and methods: This is a retrospective analysis of 10 urologic centres in Poland. Data regarding major oncological procedures performed after the COVID-19 pandemic outbreak (March 15, 2020 - May 31, 2020) were evaluated and compared with data from the respective period in 2019. Results: Between March 15, 2020 and May 31, 2020, a total of 968 oncological procedures were performed in participating centres. When compared to the respective period in 2019 (1063 procedures) the overall number of surgeries declined by 8.9%. The reduction was observed for transurethral resection of bladder tumour (TURBT) (20.1%) and partial nephrectomies (PN) (16.5%). Surgical activity considering radical nephrectomy (RN), nephroureterectomy (NU), and radical prostatectomy (RP) remained relatively unchanged, whereas radical cystectomy (RC) burden showed a significant increase (90.9%). Characteristics of patients treated with TURBT, RC, NU, PN, and RN did not differ significantly between the compared periods, whereas RP in the COVID-19 period was performed more frequently in patients with a higher grade group (p = 0.028) and positive digital rectal examination (p = 0.007). Conclusions: Surgical activity for urological cancers in Poland has been maintained during the first wave of the COVID-19 pandemic. The Polish strategy in the initial period of the COVID-19 crisis mirrors the scenario of hard initial lockdown followed by adaptive lockdown, during which oncological care remained undisrupted and did not require particular priority triage.

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.

De Novo Detrusor Underactivity and Other Urodynamic Findings after Radical Prostatectomy: A Systematic Review.

Background and objectives: The aim of this systematic review is to evaluate the impact of radical prostatectomy (RP) on bladder function, with special attention towards detrusor underactivity investigated with the means of urodynamic evaluation. Materials and Methods: The review was performed in accordance with the PRISMA statement and was registered in the PROSPERO (ID#: CRD42020223480). The studied population was limited to men with prostate cancer who underwent urodynamic study prior to and after radical prostatectomy. Eight hundred twenty-seven studies were screened, with twenty-five finally included. A qualitative analysis was performed. Rates of detrusor underactivity (DU) before surgery were reported in eight studies and ranged from 1.6% to 75% (median of 40.8%). DU occurred de novo after RP in 9.1% to 37% of patients (median of 29.1%). On the other hand, preexisting DU resolved in 7% to 35.5% of affected men. Detrusor overactivity (DO) was the most frequently reported outcome, being assessed in 23 studies. The rate of DO preoperatively was from 5% to 76% (median of 25%). De novo was reported in 2.3-54.4% of patients (median of 15%) and resolved after RP in 19.6% to 87.5% (median of 33%) of affected patients. Baseline rates of bladder outlet obstruction (BOO) varied between studies from 19% to 59.3%, with a median of 27.8%. The most pronounced change after surgery was the resolution of BOO in 88% to 93.8% (median of 92%) of affected patients. Results: Rates of de novo impaired bladder compliance (IBC) varied from 3.2% to 41.3% (median of 13.3%), whereas the resolution of IBC was reported with rates ranging from 0% to 47% (median of 4.8%). Conclusions: BOO, DO, and DU are frequently diagnosed in men scheduled for RP. BOO is improved after RP in most patients; however, there is still a substantial rate of patients with de novo DU as well as DO which may impair functional outcomes and quality of life.

Role of Radiomics in the Prediction of Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Radiomics is a field of science that aims to develop improved methods of medical image analysis by extracting a large number of quantitative features. New data have emerged on the successful application of radiomics and machine-learning techniques to the prediction of muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the diagnostic performance of radiomic techniques in predicting MIBC. EVIDENCE ACQUISITION: The literature search for relevant studies up to July 2020 was performed in the PubMed and EMBASE databases by two independent reviewers. The meta-analysis was inducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inclusion criteria comprised studies that evaluated the diagnostic accuracy of radiomic models in predicting MIBC and used pathological examination as the reference standard. For bias assessment, Quality Assessment of Diagnostic Accuracy Studies-2 and Radiomic Quality Score were used. Weighted summary proportions were used to calculate pooled sensitivity and specificity. A linear mixed model was implemented to calculate the hierarchical summary receiver-operating characteristic (HSROC). Meta-regression analyses were performed to explore heterogeneity. EVIDENCE SYNTHESIS: Eight studies with a total of 860 patients were included. The summary estimates for sensitivity and specificity in predicting MIBC were 82% (95% confidence interval [CI]: 77-86%) and 81% (95% CI: 76-85%), respectively. The area under HSROC was 0.88. There were no relevant heterogeneity in diagnostic accuracy measures (I2 = 33% and 41% for sensitivity and specificity, respectively), which was confirmed by a subsequent meta-regression analysis. CONCLUSIONS: Radiomics shows high diagnostic performance in predicting MIBC. Despite differences in approaches, radiomic models were relatively homogeneous in their diagnostic accuracy. With further improvements, radiomics has the potential to become a useful adjunct in clinical management of bladder cancer. PATIENT SUMMARY: Rapidly evolving imaging analysis methods using artificial intelligence algorithms, called radiomics, show high diagnostic performance in predicting muscle-invasive bladder cancer.

External validation of a magnetic resonance imaging-based algorithm for prediction of side-specific extracapsular extension in prostate cancer.

INTRODUCTION: Recently developed algorithm for prediction of side-specific extracapsular extension (ECE) of prostate cancer required validation before being recommended to use. The algorithm assumed that ECE on a particular side was not likely with same side maximum tumor diameter (MTD) <15 mm AND cancerous tissue in ipsilateral biopsy <15% AND PSA <20 ng/mL (both sides condition). The aim of the study was to validate this predictive tool in patients from another department. MATERIAL AND METHODS: Data of 154 consecutive patients (308 prostatic lateral lobes) were used for validation. Predictive factors chosen in the development set of patients were assessed together with other preoperative parameters using logistic regression to check for their significance. Sensitivity, specificity, negative and positive predictive values were calculated for bootstrapped risk-stratified validation dataset. RESULTS: Validation cohort did not differ significantly from development cohort regarding PSA, PSA density, Gleason score (GS), MTD, age, ECE and seminal vesicle invasion rate. In bootstrapped data set (n = 200 random sampling) algorithm revealed 70.2% sensitivity (95% confidence interval (CI) 58.8-83.0%), 49.9% specificity (95%CI: 42.0-57.7%), 83.9% negative predictive value (NPV; 95%CI: 76.1-91.4%) and 31.1% positive predictive value (PPV; 95%CI: 19.6-39.7%). When limiting analysis to high-risk patients (Gleason score >7) the algorithm improved its performance: sensitivity 91%, specificity 47%, PPV 53%, NPV 89%. CONCLUSIONS: Analyzed algorithm is useful for identifying prostate lobes without ECE and deciding on ipsilateral nerve-sparing technique during radical prostatectomy, especially in patients with GS >7. Due to significant number of false positives in case of: MTD ≥15 mm OR cancer in biopsy ≥15% OR PSA ≥20 ng/mL additional evaluation is necessary to aid decision-making.

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.

Prostate Imaging Reporting and Data System in prostate cancer staging and planning for radical prostatectomy.

INTRODUCTION: The Prostate Imaging Reporting and Data System (PI-RADS) was mainly developed for the purposes of prostate cancer (PCa) detection. However, its widespread use suggests that it may play a role in a preoperative workup prior to endoscopic radical prostatectomy (ERP). AIM: To evaluate the prognostic value of PI-RADS in predicting extraprostatic extension (EPE) and its influence on surgical planning of ERP. MATERIAL AND METHODS: The analysis involved data of 154 consecutive prostate cancer patients, in whom multiparametric 3.0T magnetic resonance imaging (mpMRI) was performed before ERP. Standard descriptive assessment of mpMRI images was compared with the PI-RADS system with respect to prostate cancer staging and subsequent potential surgical template adjustment. RESULTS: PI-RADS significantly outperformed the standard way of mpMRI reporting in staging (AUC = 0.615 vs. 0.552, p = 0.036) with PI-RADS 5 established as the best threshold. After reevaluation of imaging, the initial surgical plan was modified based on mpMRI in terms of feasibility and extent of neurovascular bundle preservation during ERP on 96 (31.2%) sides, while on the remaining 212 (68.8%) sides the templates were left unchanged. Decisions based on mpMRI were not associated with increased risk of a positive surgical margin (PSM). CONCLUSIONS: The PI-RADS outperforms the standard staging method using mpMRI and may assist the decision-making process regarding the extent of resection during ERP without increasing the risk of PSM.

Clinical utility of MRI in the decision-making process before radical prostatectomy: Systematic review and meta-analysis.

CONTEXT: Magnetic resonance imaging (MRI) is currently the most accurate imaging modality to assess local prostate cancer stage. Despite a growing body of evidence, incorporation of MRI images into decision-making process concerning surgical template of radical prostatectomy, is complex and still poorly understood. OBJECTIVE: We sought to determine the value of MRI in preoperative planning before radical prostatectomy. MATERIALS AND METHODS: Systematic search through electronic PubMed, EMBASE, and Cochrane databases from 2000 up to April 2018 was performed. Only studies that used preoperative MRI in decision-making process regarding extension of resection in patients with prostate cancer, in whom radical prostatectomy was an initial form of treatment were included into analysis. Their quality was scored by Risk Of Bias In Non-Randomized Studies of Interventions system. Meta-analysis was performed to calculate the weighted summary proportion under the fixed or random effects model as appropriate and pooled effects were depicted on forest plots. RESULTS: The results showed that the preoperative MRI led to the modification of initial surgical template in one third of cases (35%). This occurred increasingly with the rising prostate cancer-risk category: 28%, 33%, 52% in low-, intermediate- and high-risk group, respectively. Modification of neurovascular bundle-sparing surgery based on MRI appeared to have no impact on the positive surgical margin rate. The decision based on MRI was correct on average in 77% of cases and differed across prostate cancer-risk categories: 63%, 75% and 91% in low-, intermediate- and high-risk group, accordingly. CONCLUSIONS: In summary, MRI has a considerable impact on the decision-making process regarding the extent of resection during radical prostatectomy. Adaptation of MRI images by operating surgeons has at worst no significant impact on surgical margin status, however its ability to decrease the positive surgical margin rates remains unconfirmed.

3.0-T multiparametric magnetic resonance imaging modifies the template of endoscopic, conventional radical prostatectomy in all cancer risk categories.

INTRODUCTION: We aimed to evaluate the diagnostic performance of 3.0-T multiparametric magnetic resonance imaging (mpMRI) in preoperative staging of prostate cancer (PCa) and its influence on the extent of resection during endoscopic radical prostatectomy (ERP) among cancer risk groups. MATERIAL AND METHODS: The data of 154 patients with PCa in whom mpMRI was performed prior to ERP between 2011 and 2015 were included. The initial decision whether to perform neurovascular bundle (NVB) sparing surgery was based on EAU guidelines. mpMRI images were reevaluated prior to prostatectomy to modify the surgical template. Imaging was compared with pathological reports to investigate the diagnostic performance of mpMRI. RESULTS: The surgical template was modified in 69 (44.8%) patients after reevaluation of mpMRI. More preserving NVB sparing was attempted in 17 (11.0%) men, in whom NVB would have been resected if mpMRI had not been available. More aggressive NVB resection was performed in 52 (33.8%) men, in whom innervation would have been spared if basing solely based on guidelines. Among all PCa risk groups mpMRI had an impact on the surgical template with more aggressive surgery in 63.0% and 33.3% of men in the low- and intermediate-risk group, respectively, and more preserving in 21.4% of the high-risk patients. The change in extent of resection was not correlated with a higher risk of positive surgical margins (p = 0.196). CONCLUSIONS: Preoperative mpMRI exerts a significant impact on decision making concerning the extent of resection during ERP irrespective of the PCa risk group.

HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies.

Downregulation of CD20, a molecular target for monoclonal antibodies (mAbs), is a clinical problem leading to decreased efficacy of anti-CD20-based therapeutic regimens. The epigenetic modulation of CD20 coding gene (MS4A1) has been proposed as a mechanism for the reduced therapeutic efficacy of anti-CD20 antibodies and confirmed with nonselective histone deacetylase inhibitors (HDACis). Because the use of pan-HDACis is associated with substantial adverse effects, the identification of particular HDAC isoforms involved in CD20 regulation seems to be of paramount importance. In this study, we demonstrate for the first time the role of HDAC6 in the regulation of CD20 levels. We show that inhibition of HDAC6 activity significantly increases CD20 levels in established B-cell tumor cell lines and primary malignant cells. Using pharmacologic and genetic approaches, we confirm that HDAC6 inhibition augments in vitro efficacy of anti-CD20 mAbs and improves survival of mice treated with rituximab. Mechanistically, we demonstrate that HDAC6 influences synthesis of CD20 protein independently of the regulation of MS4A1 transcription. We further demonstrate that translation of CD20 mRNA is significantly enhanced after HDAC6 inhibition, as shown by the increase of CD20 mRNA within the polysomal fraction, indicating a new role of HDAC6 in the posttranscriptional mechanism of CD20 regulation. Collectively, our findings suggest HDAC6 inhibition is a rational therapeutic strategy to be implemented in combination therapies with anti-CD20 monoclonal antibodies and open up novel avenues for the clinical use of HDAC6 inhibitors.

Contralateral adrenal metastasis from renal cell carcinoma with tumor thrombus in the adrenal vein: a case report.

A 64-year-old woman presented with contralateral right adrenal metastasis with adrenal vein thrombus, which was diagnosed many years after left nephrectomy with adrenalectomy due to renal cell cancer. The patient underwent right adrenalectomy with adrenal vein tumor thrombectomy for treatment. The pathologic examination confirmed metastatic clear cell carcinoma. The remote but existing risk of developing contralateral adrenal metastasis (CAM) after primary radical nephrectomy supports the idea of sparing the adrenal gland in suitable patients who undergo radical nephrectomy. Contralateral adrenal metastasis from RCC is a rare finding with the potential benefit of cure after resection. Care must be taken in preoperative diagnostics, as this metastasis is capable of causing inferior vena cava tumor thrombus via the suprarenal venous route. According to our knowledge, our case is the second similar entity described in literature so far.