The effect of ultrasound-guided rectus sheath block on postoperative analgesia in robot assisted prostatectomy: A randomized controlled trial.

BACKGROUND: Postoperative pain continues to represent an important problem even after minimally invasive robotic-assisted laparoscopic radical prostatectomy, which results in discomfort in the postoperative period and sometimes prolongs hospital stays. Regional anesthesia and analgesia techniques are used in addition to systemic analgesics with the multimodal approach in postoperative pain management. Ultrasound-guided fascial plane blocks are becoming increasingly important, especially in minimally invasive surgeries. Another important cause of discomfort is urinary catheter pain. The present randomized controlled study investigated the effect of rectus sheath block on postoperative pain and catheter-related bladder discomfort in robotic prostatectomy operations. METHODS: This randomized controlled trial was conducted from March to August 2022. Written informed consent was obtained from all participants. Approval for the study was granted by the Clinical Research Ethics Committee. All individuals provided written informed consent, and adults with American Society of Anesthesiologists Physical Condition classification I to III planned for robotic prostatectomy operations under general anesthesia were enrolled. Following computer-assisted randomization, patients were divided into 2 groups, and general anesthesia was induced in all cases. Rectus sheath block was performed under general anesthesia and at the end of the surgery. No fascial plane block was applied to the patients in the non-rectus sheath block (RSB) group.Postoperative pain and urinary catheter pain were assessed using a numerical rating scale. Fentanyl was planned as rescue analgesia in the recovery room. In case of numerical rating scale scores of 4 or more, patients were given 50 µg fentanyl IV, repeated if necessary. The total fentanyl dose administered was recorded in the recovery room. IV morphine patient-controlled analgesia was planned for all patients. All patients' pain (postoperative pain at surgical site and urethral catheter discomfort) scores and total morphine consumption in the recovery unit and during follow-ups on the ward (3, 6, 12, and 24 hours) in the postoperative period were recorded. RESULTS: Sixty-one patients were evaluated. Total tramadol consumption during follow-up on the ward was significantly higher in the non-RSB group. Fentanyl consumption in the postanesthesia care unit was significantly higher in the non-RSB group. Total morphine consumption was significantly lower in the RSB group at 0 to 12 hours and 12 to 24 hours. Total opioid consumption was 8.81 mg in the RSB group and 19.87 mg in the non-RSB group. A statistically significant decrease in urethral catheter pain was noted in the RSB group at all time points. CONCLUSION: RSB exhibits effective analgesia by significantly reducing postoperative opioid consumption in robotic prostatectomy operations.

Machine learning prediction of Gleason grade group upgrade between in-bore biopsy and radical prostatectomy pathology.

This study aimed to enhance the accuracy of Gleason grade group (GG) upgrade prediction in prostate cancer (PCa) patients who underwent MRI-guided in-bore biopsy (MRGB) and radical prostatectomy (RP) through a combined analysis of prebiopsy and MRGB clinical data. A retrospective analysis of 95 patients with prostate cancer diagnosed by MRGB was conducted where all patients had undergone RP. Among the patients, 64.2% had consistent GG results between in-bore biopsies and RP, whereas 28.4% had upgraded and 7.4% had downgraded results. GG1 biopsy results, lower biopsy core count, and fewer positive cores were correlated with upgrades in the entire patient group. In patients with GG > 1 , larger tumor sizes and fewer biopsy cores were associated with upgrades. By integrating MRGB data with prebiopsy clinical data, machine learning (ML) models achieved 85.6% accuracy in predicting upgrades, surpassing the 64.2% baseline from MRGB alone. ML analysis also highlighted the value of the minimum apparent diffusion coefficient ( ADC min ) for GG > 1 patients. Incorporation of MRGB results with tumor size, ADC min value, number of biopsy cores, positive core count, and Gleason grade can be useful to predict GG upgrade at final pathology and guide patient selection for active surveillance.

De-Escalation of Therapy for Prostate Cancer.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men with around 1.4 million new cases every year. In patients with localized disease, management options include active surveillance (AS), radical prostatectomy (RP; with or without pelvic lymph node dissection), or radiotherapy to the prostate (with or without pelvic irradiation) with or without hormonotherapy. In advanced disease, treatment options include systemic treatment(s) and/or treatment to primary tumour and/or metastasis-directed therapies (MDTs). Specifically, in advanced stage, the current trend is earlier intensification of treatment such as dual or triple combination systemic treatments or adding treatment to primary and MDT to systemic treatment. However, earlier treatment intensification comes with the cost of increased morbidity and mortality resulting from drug-/treatment-related side effects. The main goal is and should be to provide the best possible care and oncologic outcomes with minimum possible side effects. This chapter will explore emerging possibilities to de-escalate treatment in PCa driven by enhanced insights into disease biology and the natural course of PCa such as AS in intermediate-risk disease or salvage versus adjuvant radiotherapy in post-RP patients. Considerations arising from advancements in PCa imaging and technological advancements in surgical and radiation therapy techniques including omitting pelvic lymph node dissection in the era of prostate-specific membrane antigen positron emitting tomography, the potential of MDT to delay/omit systemic treatment in metachronous oligorecurrence, and the efficacy of hypofractionation schemes compared with conventional fractionated radiotherapy will be discussed.

Radioligand Therapy With 177 Lu-PSMA-I&T in Patients With Metastatic Prostate Cancer : Oncological Outcomes and Toxicity Profile.

INTRODUCTION: This study aimed to investigate the oncological outcomes and toxicity profile of 177 Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177 Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria. RESULTS: In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177 Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC. CONCLUSIONS: 177 Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177 Lu-PSMA-I&T RLT in the management of metastatic prostate cancer.

Intraoperative Frozen Section via Neurosafe During Robotic Radical Prostatectomy in the Era of Preoperative Risk Stratifications and Primary Staging With mpMRI and PSMA-PET CT: Is There a Perfect Candidate?

BACKGROUND: We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). METHODS: Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. RESULTS: A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p = .01) and PIRADS 5 (p = .002) findings and had more D'Amico high risk (DAHR) patients (p = .08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p = .4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p = .02). CONCLUSION: RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously.

Diagnostic Performance of 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography to Monitor Treatment Response in Patients with Metastatic Prostate Cancer: The Concordance Between Biochemical Response and Prostate-specific Membrane Antigen Results.

BACKGROUND: Treatment response is traditionally monitored using prostate-specific antigen (PSA) and conventional imaging in patients with metastatic prostate cancer (mPCa). OBJECTIVE: To assess the diagnostic performance of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) when monitoring mPCa patients receiving systemic treatment and also to investigate the concordance between PSMA PET response according to the PSMA PET progression (PPP) criteria and biochemical response. DESIGN, SETTING, AND PARTICIPANTS: A total of 96 patients with 68Ga-PSMA-11 PET/CT-detected mPCa at baseline PSMA PET/CT (bPSMA) who underwent at least one follow-up scan after receiving systemic treatment were included in the study. PSA levels at bPSMA and follow-up PSMA PET (fPSMA) scans were recorded. The PPP criteria were used to define PSMA progression. Biochemical progression was defined as ≥25% increase in PSA. PSMA PET and PSA responses were dichotomized into progressive disease (PD) versus non-PD, and the concordance between PSA and PSMA responses was evaluated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The concordance between PSA and PSMA PET responses was presented using frequencies, percentages, and Cohen's kappa test. RESULTS AND LIMITATIONS: A total of 345 serial PSMA PET/CT (96 bPSMA and 249 fPSMA) scans were evaluated. The positivity rates of PSMA PET scans for PSA levels of <0.01, 0.01-0.2, 0.2-4, and >4 ng/ml were 55.6%, 75.0%, 100%, and 98.8%, respectively. PSA and PSMA responses showed moderate-to-high concordance (Cohen's κ = 0.623, p < 0.001). PSA-PSMA discordance was detected in 39 scans (17%). The most common cause of discordance was the discordant results between different metastatic lesions (16/28, 57.1%) in patients with PPP without PSA progression and local progression in prostate (n = 7/11, 63.6%) in patients with PSA progression without PPP. CONCLUSIONS: PSMA PET/CT showed very high detection rates of malignant lesions even at very low PSA values and showed significant concordance with PSA response when monitoring treatment response in patients receiving systemic treatment for mPCa. PATIENT SUMMARY: This study describes that prostate-specific membrane antigen positron emission tomography (PSMA PET), a new sensitive imaging tool, can detect malignant lesions even at very low prostate-specific antigen values when monitoring metastatic prostate cancer. The PSMA PET response and biochemical response showed significant concordance, and the reason for discordant results seems to be the different responses of metastatic lesions and prostatic lesions to systemic treatment.

Prostate-specific Membrane Antigen Positron Emission Tomography as a Biomarker to Assess Treatment Response in Patients with Advanced Prostate Cancer.

CONTEXT: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has superior accuracy for detection of metastatic lesions in patients with prostate cancer (PC). Although PSMA PET has a prominent role in primary and secondary imaging of PC, data on its role in assessing treatment response in advanced PC are limited. OBJECTIVE: To review current data in the literature regarding the impact of antiandrogen therapy on PSMA expression of metastatic sites and the role of serial (baseline and at least 1 follow-up scan) PSMA PET to assess treatment response in patients with metastatic PC. EVIDENCE ACQUISITION: A comprehensive literature search in the PubMed database was performed using the terms "PSMA expression prostate", "PSMA regulation", "PSMA PET response assessment", and "serial PSMA PET". EVIDENCE SYNTHESIS: Serial PSMA PET studies (baseline and at least 1 follow-up scan) provide valuable data regarding PSMA expression changes after systemic treatment in patients with metastatic PC. PSMA PET-detected flare and upregulation of PSMA expression following hormonal intervention seem to be early events resolving after 3 mo of treatment. PSMA PET imaging is essential in selecting patients for 177Lu-PSMA radioligand therapy (RLT). Growing evidence favors its use in assessing treatment responses after RLT. Preliminary evidence indicates the value of PSMA PET for assessment of the treatment response in patients receiving systemic treatment other than RLT for metastatic PC. CONCLUSIONS: PSMA flare following antiandrogen therapy seems to be an early event and thus PET scans should be performed no earlier than 3 mo after the start of treatment. PSMA PET has a promising role in tailoring treatment according to the specific needs of individual patients and assessing responses following systemic treatment in patients with advanced PC. PATIENT SUMMARY: This review describes how a sensitive imaging method can be used to assess the tumor response to treatment for metastatic prostate cancer.

Postchemotherapy robotic retroperitoneal lymph node dissection for non-seminomatous germ cell tumors in the lateral decubitus position: oncological and functional outcomes.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) is recommended for residual masses following chemotherapy for non-seminomatous germ cell tumors (NSGCT). Recently, aberrant recurrence patterns were reported in patients who underwent robotic RPLND. We aimed to evaluate perioperative safety in addition to functional and early oncological outcomes of postchemotherapy robotic RPLND (pcR-RPLND) for NSGCT. METHODS: A total of 25 patients with NSGCT who underwent a pcR-RPLND between January 2011 and June 2022 were evaluated retrospectively. Descriptive statistics were provided for demographics, clinical characteristics, intraoperative and postoperative parameters. Functional and oncological outcomes were recorded. RESULTS: The median patient age was 28.9 years (IQR 21.5-32.4). The median retroperitoneal tumor size was 2.6 cm (IQR 1.5-3.5). Intraoperative complications occurred in only one case and the open conversion rate was 12%. There were seven cases with postoperative complications (Clavien grade II: 5 and IIIa: 2). Patients were followed for a median of 33.2 months (IQR 14.8-43.0). Antegrade ejaculation was preserved in 85.7% of the patients. Two patients (8%) relapsed and both had out-of-field recurrences at unusual sites (perinephric fat and omentum). Of those, one patient died (4%) of testicular cancer. CONCLUSION: pcR-RPLND is a feasible and technically reproducible procedure with favorable perioperative morbidity, low rate of complications, and acceptable postoperative ejaculatory function. Although the recurrence rate was low (8%), recurrences were observed at unusual sites. Further studies are required to investigate any association between the robotic approach and aberrant recurrence patterns.

The role of the size and number of index lesion in the diagnosis of clinically significant prostate cancer in patients with PI-RADS 4 lesions who underwent in-bore MRI-guided prostate biopsy.

PURPOSE: To evaluate the contribution of the size and number of the sampled lesions to the diagnosis of clinically significant prostate cancer (CSPC) in patients who had PI-RADS 4 lesions. METHODS: In this retrospective study, a total of 159 patients who had PI-RADS 4 lesions and underwent In-bore MRI-Guided prostate biopsy were included. Patients with a lesion classified as Grade Group 2 and above were considered to have CSPC. Univariate and multivariate regression analyses were used to evaluate the factors affecting the diagnosis of prostate cancer (PCa) and CSPC. RESULTS: A great majority (86.8%) of the patients were biopsy-naïve. About three-fourths (71.7%) had PCa, and half (54.1%) had CSPC. When the patients were divided into three groups according to the index lesion size (< 5 mm, 5-10 mm, and > 10 mm), the prevalence of PCa was 64.3, 67.5, and 82.4% and the prevalence of CSPC was 42.9, 51.2, and 64.7%, respectively. In multivariate analysis, age, index lesion size, prostate volume (< 50 ml) and being biopsy-naïve were found significant for PCa, while age and prostate volume (< 50 ml) were significant for CSPC. CONCLUSION: The number of lesions was found to be insignificant in predicting PCa and CSPC. While the size of PI-RADS 4 lesions was significant in predicting PCa, it had no significance in detecting CSPC.

Experiences of perioperative nurses with robotic-assisted surgery: a systematic review of qualitative studies.

To determine the experiences of perioperative nurses with robotic-assisted surgery is needed to improve the robotic-assisted surgery practices. This study systematically reviewed and analysed the qualitative studies concerning perioperative nurses' experiences of robotic-assisted surgery. This systematic literature review included studies up to December 2020. The study data were analysed using inductive content analysis. This systematic review included six articles. There were a total of 71 nurses who participated in the included articles (min = 6, max = 17). Their mean age was 35.7, and their experience in robotic-assisted surgery ranged from 8 months to 10 years. Content analysis generated six categories: adaptation to robotic-assisted surgery technology, the importance of teamwork in robotic-assisted surgery, changing tasks and responsibilities in robotic-assisted surgery, training requirements for robotic-assisted surgery, the effects of robotic-assisted surgery on patients and patient safety, and difficulties with robotic-assisted surgery. A variety of themes and sub-themes emerged in these categories. The review highlights the importance of developing new ways of thinking about the assessment and management of disruptions, developing different teamwork patterns and communication skills, and overcoming the challenges involved in technologically advanced surgeries. Nurses' roles in robotic technology should be redefined in healthcare. Nurses should learn how to adapt to advancing technology and how to supplement and enhance their skills.

Fluorescence-guided extended pelvic lymphadenectomy during robotic radical prostatectomy.

We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectively. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements in staging and oncologic outcomes may also be seen in intermediate- and high-risk patients.

MRI as a screening tool for prostate cancer: current evidence and future challenges.

PURPOSE: Prostate cancer (PCa) screening, which relies on prostate-specific antigen (PSA) testing, is a contentious topic that received negative attention due to the low sensitivity and specificity of PSA to detect clinically significant PCa. In this context, due to the higher sensitivity and specificity of magnetic resonance imaging (MRI), several trials investigate the feasibility of "MRI-only" screening approaches, and question if PSA testing may be replaced within prostate cancer screening programs. METHODS: This narrative review discusses the current literature and the outlook on the potential of MRI-based PCa screening. RESULTS: Several prospective randomized population-based trials are ongoing. Preliminary study results appear to favor the "MRI-only" approach. However, MRI-based PCa screening programs face a variety of obstacles that have yet to be fully addressed. These include the increased cost of MRI, lack of broad availability, differences in MRI acquisition and interpretation protocols, and lack of long-term impact on cancer-specific mortality. Partly, these issues are being addressed by shorter and simpler MRI approaches (5-20 min bi-parametric MRI), novel quality indicators (PI-QUAL) and the implementation of radiomics (deep learning, machine learning). CONCLUSION: Although promising preliminary results were reported, MRI-based PCa screening still lack long-term data on crucial endpoints such as the impact of MRI screening on mortality. Furthermore, the issues of availability, cost-effectiveness, and differences in MRI acquisition and interpretation still need to be addressed.

Pathological Accuracy in Prostate Cancer: Single-Center Outcomes of 3 Different Magnetic Resonance Imaging-Targeted Biopsy Techniques and Random Systematic Biopsy.

OBJECTIVE: The aim of this study is to compare systematic, cognitive fusion, in-bore, and software fusion prostate biopsies regarding rates of and risk factors for pathological upgrading. MATERIAL AND METHODS: Charts of 291 patients with systematic biopsy (n = 105), magnetic resonance imaging- targeted cognitive fusion (n = 58), in-bore (n = 68), and software fusion biopsy (n = 60), and who subsequently underwent radical prostatectomy were retrospectively evaluated. The degree of similarity between the grade groups reported in the biopsy and radical prostatectomy pathology results was recorded. Analyses of the associated factors for concordance and discordance were performed with univariate and multivariate methods. RESULTS: The concordance rates were as follows: systematic biopsy = 42.8%, cognitive fusion-targeted biopsy = 50%, in-bore fusion-targeted biopsy = 61.8, and software fusion biopsy = 58.4%. The upgrade rate of systematic biopsy (46.6%) was higher than cognitive fusion-targeted biopsy (27.6%), in-bore fusiontargeted biopsy (26.4%), and software fusion-targeted biopsy (18.3%). The number of positive cores was significantly associated with grade group concordance for the systematic biopsy group (P = .040). Within the cognitive fusion-targeted biopsy cohort, number of positive cores was the only parameter that exhibited a significant association with grade group concordance in multivariate analysis (P = .044). Considering the in-bore fusion-targeted biopsy group, maximum tumor length was statistically significant (P = .021). In the software fusion-targeted biopsy group, low prostate volume was found to be the only significant predictor for grade group accordance (P = .021). CONCLUSION: Magnetic resonance imaging-targeted biopsy techniques showed higher concordance and lower upgrade rates compared to systematic biopsy. For systematic biopsy and cognitive fusion-targeted biopsy, the number of positive cores was associated with grade group concordance, while maximum tumor length in in-bore fusion-targeted biopsy and low prostate volume for in-bore fusion-targeted biopsy were associated with grade group concordance. Among the MRI-targeted biopsy methods, in-bore fusion-targeted biopsy and software fusion-targeted biopsy were more accurate than cognitive fusion-targeted biopsy in terms of grade group.

Quantitative Phosphoproteomics Analysis Uncovers PAK2- and CDK1-Mediated Malignant Signaling Pathways in Clear Cell Renal Cell Carcinoma.

Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers in both men and women and causes more than 140,000 deaths worldwide every year. In order to elucidate the underlying molecular mechanisms orchestrated by phosphorylation modifications, we performed a comprehensive quantitative phosphoproteomics characterization of ccRCC tumor and normal adjacent tissues. Here, we identified 16,253 phosphopeptides, of which more than 9000 were singly quantified. Our in-depth analysis revealed 600 phosphopeptides to be significantly differentially regulated between tumor and normal tissues. Moreover, our data revealed that significantly up-regulated phosphoproteins are associated with protein synthesis and cytoskeletal re-organization which suggests proliferative and migratory behavior of renal tumors. This is supported by a mesenchymal profile of ccRCC phosphorylation events. Our rigorous characterization of the renal phosphoproteome also suggests that both epidermal growth factor receptor and vascular endothelial growth factor receptor are important mediators of phospho signaling in RCC pathogenesis. Furthermore, we determined the kinases p21-activated kinase 2, cyclin-dependent kinase 1 and c-Jun N-terminal kinase 1 to be master kinases that are responsible for phosphorylation of many substrates associated with cell proliferation, inflammation and migration. Moreover, high expression of p21-activated kinase 2 is associated with worse survival outcome of ccRCC patients. These master kinases are targetable by inhibitory drugs such as fostamatinib, minocycline, tamoxifen and bosutinib which can serve as novel therapeutic agents for ccRCC treatment.

Radical nephroureterectomy for UTUC conferred survival benefits irrespective of age and comorbidities.

PURPOSE: We investigated the effects of age, American Society of Anesthesiologists Physical Status Classification (ASA) grading and Charlson Comorbidity Index (CCI) on the survival outcomes of upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry was an international, multicenter study on patients with UTUC. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to their age (≤ 70 and > 70 years old) and ASA grade (I-II and III-V)/CCI (0-1 and ≥ 2). RESULTS: A total of 2352 patients were included in this study. Patients aged ≤ 70 years with ASA grading of I-II (p = 0.002), and patients aged ≤ 70 years with a CCI of 0-1 (p = 0.002) had the best OS. Upon multivariate analysis, both in patients aged ≤ 70 and > 70 years, ASA grading and CCI were not significantly associated with OS. Patients aged ≤ 70 years with ASA grading of III-IV (p = 0.024) had the best DFS. When stratified according to age and CCI, no significant difference in DFS was noted. Upon multivariate analysis, radical nephroureterectomy (RNU) was significantly associated with better DFS in patients aged ≤ 70 and > 70 years; CCI of ≥ 3 was significantly associated with worse DFS in patients ≤ 70 years; ASA grading was not associated with DFS in patients aged ≤ 70 and > 70 years. CONCLUSIONS: A high ASA grading and CCI should not be considered contraindications for RNU. RNU should be considered even in elderly patients when it is deemed feasible and achievable after a geriatric assessment.

Histologically benign PI-RADS 4 and 5 lesions contain cancer-associated epigenetic alterations.

BACKGROUND: The detection rate of clinically significant prostate cancer has improved with the use of multiparametric magnetic resonance imaging (mpMRI). Yet, even with MRI-guided biopsy 15%-35% of high-risk lesions (Prostate Imaging-Reporting and Data System [PI-RADS] 4 and 5) are histologically benign. It is unclear if these false positives are due to diagnostic/sampling errors or pathophysiological alterations. To better understand this, we tested histologically benign PI-RAD 4 and 5 lesions for common malignant epigenetic alterations. MATERIALS AND METHODS: MRI-guided in-bore biopsy samples were collected from 45 patients with PI-RADS 4 (n = 31) or 5 (n = 14) lesions. Patients had a median clinical follow-up of 3.8 years. High-risk mpMRI patients were grouped based on their histology into biopsy positive for tumor (BPT; n = 28) or biopsy negative for tumor (BNT; n = 17). From these biopsy samples, DNA methylation of well-known tumor suppressor genes (APC, GSTP1, and RARß2) was quantified. RESULTS: Similar to previous work we observed high rates of promoter methylation at GSTP1 (92.7%), RARß2 (57.3%), and APC (37.8%) in malignant BPT samples but no methylation in benign TURP chips. Interestingly, similar to the malignant samples the BNT biopsies also had increased methylation at the promoter of GSTP1 (78.8%) and RARß2 (34.6%). However, despite these epigenetic alterations none of these BNT patients developed prostate cancer, and those who underwent repeat mpMRI (n = 8) demonstrated either radiological regression or stability. CONCLUSIONS: Histologically benign PI-RADS 4 and 5 lesions harbor prostate cancer-associated epigenetic alterations.

The Impact of Visible Tumor (PI-RADS ≥ 3) on Upgrading and Adverse Pathology at Radical Prostatectomy in Low Risk Prostate Cancer Patients: A Biopsy Core Based Analysis.

BACKGROUND: The objective of this study was to investigate the impact of the characteristics of a single visible tumor (Prostate Imaging-Reporting and Data System [PI-RADS]≥3) on upgrading and adverse pathology at radical prostatectomy (RP) in biopsy naïve low risk prostate cancer (PCa) patients. MATERIALS AND METHODS: We retrospectively reviewed 64 biopsy naïve patients from 3 different referral centers between 2018 and 2020 with a PSA<10, cT1c disease, a single PI-RADS≥ 3 index lesion in multiparametric-MRI (mp-MRI), all bearing a GG 1 tumor sampled software fusion biopsy, who underwent RP. Preoperative clinical variables including the localization, number and tumor burden of positive cores for each PI-RADS category were related to upgrading and adverse pathology (GG>2 and/or pT3 and/or lymph node positive disease) at RP. RESULTS: Overall 37 patients (57.8%) were upgraded with a significant difference of upgrading in PI-RADS3 (30.0%) versus PI-RADS 4 (67.6%) (P = .007) and PI-RADS 4-5 (70.5%) lesions (P = .002). Thirty-three of 37 GG1 tumors were upgraded to GG2, while 6 of these 33 (18.2%) had adverse pathology as well. Overall 9 patients (14.1%) had adverse pathology at RP all harboring PI-RADS4-5 lesions. The number of positive cores differed significantly between the upgraded and nonupgraded patients. Adverse pathology group had significantly higher tumor volume at RP. CONCLUSION: PI-RADS4-5 lesions are the independent predictors of upgrading and adverse pathology in low risk PCa with visible tumors. Upgrading and adverse pathology were closely related to the number of positive combined cores reflecting the role of tumor volume. This should be kept in mind in shared decision making of an individual patient with low risk disease and a visible tumor.

Gardnerella vaginalis: Is it an Underestimated Cause of Urinary Symptoms in Males?

Objective: This study aimed to investigate the detection rate of Gardnerella vaginalis by multiplex PCR test in the genitourinary samples of male patients with suspected urethritis and related symptoms. Materials and Methods: A total of 144 male patients who presented to our department between February 2021 and October 2021, either with urinary symptoms or concerns following unprotected sex, were included in the study.A total of 128 (88.9%) first-void urine samples, 15 (10.4%) urethral swabs, and one (0.7%) semen sample were obtained. NeoPlex STI-14 Detection Multiplex PCR Kit (GeneMatrix Inc. Seongnam, South Korea) was used to investigate any of the following pathogens: Candida albicans, Chlamydia trachomatis, G. vaginalis, Mycoplasma genitalium, Mycoplasma hominis, Neisseria gonorrhoeae, Trichomonas vaginalis, Ureaplasma parvum, Ureaplasma urealyticum,herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), Treponema pallidum , Streptococcus agalactiae, and Haemophilus ducreyi. The patients with positive results for G. vaginalis were retrospectively analyzed. Results: The patients' median age was 37 (range: 21 to 71 years old). G. vaginalis was the most frequently detected microorganism (n=23; 15.9%). Other microorganisms found in order of frequency were U. urealyticum (n=19; 13.2%), U. parvum (n=15; 10.4%), C. trachomatis (n=11; 7.6%), M. genitalium (n=8; 5.6%), HSV-2 (n= 7; 4.9%), N. gonorrhoeae (n=6; 4.2), HSV-1 (n=2; 1.4%), M. hominis (n=1, 0.7%), and C. albicans (n=1, 0.7%). Fifteen patients (65%) were positive for one or two microbial agents together with G. vaginalis, while in eight patients (35%), G. vaginalis was the only isolated agent. Six of these eight patients and 14 of the remaining 15 were symptomatic. Conclusion: With the introduction of multiplex PCR tests, including those for G. vaginalis, we can expect a higher detection rate of these species of bacteria in male genitourinary samples, which could be the cause of unexplained urinary/urethral symptoms.

Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study.

BACKGROUND: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. METHODS: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. RESULTS: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). CONCLUSION: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

In-bore MRI-guided prostate biopsy in a patient group with PI-RADS 4 and 5 targets: A single center experience.

PURPOSE: To determine the diagnostic yield of magnetic resonance imaging (MRI) guided in-bore biopsy in patients with high likelihood multiparametric MRI (mpMRI) findings, regarding overall and clinically significant prostate cancer (csPCa) detection rates and concordance of biopsy and radical prostatectomy (RP) Gleason scores (GS). METHODS: This retrospective study consisted of 277 Prostate Imaging Reporting and Data System (PI-RADS) assessment category 4 and 5 targets in 246 patients (mean age, 65.7 years; median prostate specific antigen value, 7.75 ng/mL) who had undergone in-bore biopsy at our institution between 2012 and 2020. Eighty-one patients who underwent RP were eligible for the concordance analysis of biopsy and RP specimen GS. RESULTS: Overall PCa detection rates were 80.5 % per patient (198/246) and 78 % per target (216/277) and 83.5 % and 67.4 % in primary (biopsy naive) and secondary (at least one negative prior biopsy) settings. csPCa was found in 63 % overall, 66 % of patients (132/200) in the primary, and 50 % of patients (23/46) in the secondary biopsy settings (p < 0.001). The prostate cancer detection rate was 68 % and 92 % in PI-RADS 4 and 5, respectively (p < 0.001). In the radical prostatectomy subcohort, 27.2 % of patients were upgraded, 8.6 % of patients were downgraded from needle biopsy. Significant complications occurred in 1.2 % of patients. CONCLUSIONS: MRI-guided in-bore prostate biopsy has a high detection rate of csPCa in primary and secondary biopsy cohorts. Biopsy results were satisfactory in terms of the number of positive cores, cancer percentage in positive cores, and concordance of GS in needle biopsy and RP specimen.