Translational andrology and urology最新文献

Background: Many factors affect the prognosis of kidney renal clear cell carcinoma (KIRC). Early diagnosis can significantly improve the prognosis of KIRC patients. Therefore, a method needs to be developed to diagnose KIRC early, predict patient prognosis, and improve personalized treatments. The objective of this study is to utilize bioinformatics tools and public database resources to identify differentially expressed genes (DEGs) between renal cancer tissues and adjacent normal tissues, and to further screen for prognostic-related genes (PRGs) of KIRC.

Methods: KIRC was studied using R language and FunRich software and several databases, including the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham cancer data analysis Portal (UALCAN), and Tumor Immune Estimation Resource (TIMER) databases. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expression of multiple genes in KIRC and adjacent normal tissues.

Results: There were substantial differences in immune cell infiltration between the KIRC and adjacent normal tissues in the GSE40435 and GSE46699 datasets. In addition, we screened multiple PRGs of KIRC by combining the GEO and TCGA data. The UALCAN database verified that some representative PRGs were differently expressed depending on the lymph node metastasis status, grade, and stage of KIRC. The qRT-PCR results confirmed the expression of the PRGs in KIRC and adjacent normal tissues. Through the GO and KEGG analyses, interaction analysis, and TIMER database, we found that the prognosis of KIRC was closely related to immune microenvironment and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling.

Conclusions: Our findings could contribute to the prognosis prediction of KIRC, the selection of personalized treatments, and the early diagnosis of KIRC.

Background and objective: Penile prostheses are an option for the management of erectile dysfunction (ED). Over the years penile prosthesis surgery has become increasingly safe owing to improvements such as antibiotic usage, coated devices, and surgical techniques. However, infection remains a dreaded complication during prosthesis surgery. Efforts to minimize risk of infection in the perioperative period have been extensively studied. Herein, we performed a narrative review on preoperative, intraoperative, and postoperative strategies for infection prevention during placement of a penile prosthesis with a comparison of infection prevention strategies to other surgical fields.

Methods: A literature review was performed using PubMed and Google Scholar. Studies evaluating perioperative management of penile prosthesis infection were included. The following search terms were used to for our literature search: penile prosthesis, inflatable penile prosthesis, infection, prevention, perioperative management. Articles were graded based on the 2011 Oxford Centre for Evidence Based Medicine (OCEBM) guidelines and a table was generated with each intervention discussed and its level of evidence based on current literature.

Key content and findings: Optimization of patient's comorbid conditions can help reduce risk during prosthesis operations. Monitoring and optimizing a patient's glycemic control has been investigated, but the current literature does not necessarily support a strict hemoglobin A1c (HbA1c) or pre-operative blood glucose level. Surgical field preparation using chlorhexidine-based solutions has been shown to be superior to iodine-based solutions. Appropriately selected peri-operative antibiotics have also been shown to reduce infection risk. Intraoperatively, the use of coated devices in addition to a 'no touch' technique have been shown to significantly reduce the risk of inflatable penile prosthesis (IPP) infection. Post operatively, available evidence of antibiotic use has not been demonstrated to be effective in reducing infection rates.

Conclusions: Surgical infection following placement of an IPP is a devastating and morbid complication with infection rate up as high as 1-3% in virgin cases and 7-18% in revision cases. While perioperative techniques exist and have reduced risk of infection, more prospective data is needed to evaluate the clinical significance of these different approaches. More research in these areas, along with future options such as nanoparticles, antibiotic coated suture, and next generation sequencing (NGS) for bacterial pathogens, may shed light on further ways to optimize infection reduction strategies for prosthesis surgery.

Background: Partial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS).

Methods: We identified 2,832 patients with cT2-4N0M0 bladder cancer (BCa) who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS in treatment modalities in PC patients. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy [≥10 lymph node (LN) yield], and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients.

Results: Two hundred and thirty-one patients received multi-agent NAC with PC. NAC treatment with PLND was associated with significantly improved OS (P<0.001). Median OS was 43.9 months in patients treated with PC alone, while median OS was not reached in PC patients treated with NAC & PLND. Furthermore, patients who received NAC without any PLND had a median OS of 50.6 months, while those treated with PLND without NAC had a median OS of 76.5 months. This persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10 LN. Conversely, age >80 years old, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND [odds ratio (OR) 0.719, P=0.005], while NAC was more likely administered to PC patients diagnosed from 2016-2019 (OR 5.295, P<0.001). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR 2.189, P<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR 1.745, P=0.003; OR 2.465, P<0.001, respectively).

Conclusions: Despite guideline recommendations, the utilization of NAC and PLND with PC remains insufficient. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation.

Background: Gleason grade group (GG) upgrading is associated with increased biochemical recurrence (BCR), local progression, and decreased cancer-specific survival (CSS) in prostate cancer (PCa). However, descriptions of the risk factors of GG upgrading are scarce. The objective of this study was to identify risk factors and establish a model to predict GG upgrading.

Methods: There were 361 patients with PCa who underwent radical prostatectomy between May 2011 and February 2022 enrolled. Univariate and multivariate logistic regression analyses were identified and nomogram further narrowed down the contributing factors in GG upgrading. The correction curve and decision curve were used to assess the model.

Results: In the overall cohort, 141 patients had GG upgrading. But the subgroup cohort (GG ≤2) showed that 68 patients had GG upgrading. Multivariate logistic regression analysis showed that in the overall cohort, total prostate-specific antigen (tPSA) ≥10 ng/mL, systemic immune-inflammation index (SII) >379.50, neutrophil-lymphocyte ratio (NLR) >2.13, the GG of biopsy ≥3, the number of positive cores >3 were independent risk factors in GG upgrading. In the cohort of biopsy GG ≤2, multivariate logistic regression showed that the tPSA ≥10 ng/mL, SII >379.50 and the number of positive cores >3 were independent risk factors in GG upgrading. A novel model predicting GG upgrading was established based on these three parameters. The area under the curve (AUC) of the prediction model was 0.759. The C-index of the nomogram was 0.768. The calibration curves of the model showed good predictive performance. Clinical decision curves indicated clinical benefit in the interval of 20% to 90% of threshold probability and good clinical utility.

Conclusions: Combined levels of tPSA, SII and the positive biopsy cores distinguish patients with high-risk GG upgrading in the group of biopsy GG ≤2 and are helpful in the decision of treatment plans.

Background: There is ongoing debate regarding prostate cancer (PCa) screening in advanced age males, leading to treatment decisions often based on tumor staging and life expectancy. A critical gap in clinical evidence and tailored guidelines for the advanced age with PCa persists. This study aims to compare survival outcomes of various treatment approaches in this demographic.

Methods: We analyzed data from a large urological center for advanced age patients suspected of having PCa between 2012 and 2022. We collected clinical and pathological characteristics and evaluated treatment modalities, including palliative therapy and definitive therapy. Propensity score matching (PSM) analysis was implemented to reduce bias between treatment modalities. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were conducted to evaluate progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS).

Results: Out of 4,333 suspected patients, 376 individuals aged 80 years and older underwent prostate biopsy. The overall detection rate of PCa was 78.7%, with a high prevalence of high-grade tumors [International Society of Urological Pathology (ISUP) grade ≥2]. Most patients (86.5%) received palliative therapy, while 13.5% underwent definitive therapy. Patients in the definitive therapy group had lower prostate-specific antigen (PSA) values, lower tumor stage, and Charlson Comorbidity Index (CCI), longer life expectancy, and a higher Geriatric 8 (G8) score compared to the palliative therapy group. The median OS for the entire cohort was 72.0 months, with 70.0 months for palliative therapy and 96.0 months for definitive therapy. Multivariable analyses identified lymphatic and bone metastasis, as well as definitive therapy, as independent prognostic factors for PFS, CSS, and OS.

Conclusions: Advanced age patients, although a small group, have distinct characteristics, including higher PSA levels, positive biopsy rates, and pathological grading and staging. In medically fit elderly patients, especially those with localized PCa and a life expectancy of ≥5 years, definitive therapy could improve survival outcomes.

Background: Neoadjuvant chemotherapy with radical cystectomy (RC) is the preferred first-line treatment for localized muscle-invasive bladder cancer (MIBC). Due to the concern about morbidity associated with RC, the elderly population considers bladder preservation alternatives. Guidelines suggest partial cystectomy (PC) can be considered a viable option in carefully selected individuals. We used the National Cancer Database (NCDB) to compare the overall survival (OS) among octogenarians treated with PC and RC.

Methods: Using NCDB, we retrospectively evaluated individuals aged 80 years and above diagnosed with localized MIBC (cT2-4aN0M0) with tumor size less than 5 cm and urothelial histology between 2004 and 2018. Our primary cohort was divided into the RC cohort, which included patients who underwent RC with or without chemotherapy/radiotherapy, and the PC cohort, which included those who underwent PC. After propensity-matching, we compared the OS.

Results: Of 94,104 patients with MIBC, 2,528 octogenarians met our selection criteria. Among them, 313 were treated with PC, and 2,215 were treated with RC. A total of 151 (48.2%) PC patients had pelvic lymph node dissection, while 1,967 (88.8%) RC patients had lymph node dissection (P<0.001). The OS for matched PC and RC was 33.4 and 29.9 months, respectively (P=0.68). In T2 tumors, the OS for PC and RC was 37 and 33.5 months, respectively (P=0.52); for T3 tumors, the OS was 22.3 and 24.4 months, respectively (P=0.98).

Conclusions: Our study compared PC and RC in octogenarians with localized MIBC and observed that PC is safe and not inferior to RC in carefully selected octogenarians. The role of PC needs further exploration by comparing or integrating with strategies like concurrent chemoradiation to improve the oncological and survival outcomes.

Background: Artificial urinary sphinkter (AUS) are still the gold standard for treatment of male stress urinary incontinence with good clinical outcomes and high patient's reported satisfaction rate. However, more than half of the patients with an AUS will require additional procedures, most likely revisions. To introduce a novel adjustable AUS for treatment of male stress urinary incontinence and perform a preliminary clinical investigation to determine the safety and efficacy of the device.

Methods: Men with urodynamically proven SUI following radical prostatectomy (RP), transurethral resection of prostate (TURP) and pelvic injuries were implanted with the Victo-AUS. Patients with three or more previous incontinence surgeries were excluded from the series. Patients were monitored over a mean follow up of 29 months (range, 13.7-47.9 months). The device was tested for efficacy by using objective measurements of urinary leakage and continence. We used validated questionnaires at baseline and clinical follow-ups. The key outcomes were overall improvement, patients reported satisfaction and complication rate.

Results: A total of 88 patients between December 2016 and December 2019 have been enrolled in this trial. Improvement was defined as a reduction in pad usage per day (p/d) over 50% compared to baseline. In total, 70 (88%) patients were reported to be improved. Treatment success according to the definition of 0-1 p/d was accomplished in 56 (70%) patients. Urethral erosion, infection or mechanical failure occurred in 4 (5%), 4 (5%) and 1 (1.3%) patient respectively. Explantation of the device was mandatory in 6 patients due to erosion, infection or mechanical failure.

Conclusions: In this series, a continence rate of 70% was achieved with an acceptable complication-rate. These results together with a high satisfaction rate demonstrate effectiveness and safety of the Victo system in mid-term follow-up for the treatment of male SUI.

Background and objective: Even if treatment with stem cells has been shown to be safe and effective in many patients with stress urinary incontinence (SUI), there is still room for improvement using other regenerative medicine alternatives. Since the beneficial effects of stem cells are probably mediated by secretion of factors rather than by the cells themselves there is a good rationale for further exploring the therapeutic effects of the secretome and/or its components. However, homing factors such as stromal derived growth factor 1 (SDF-1; CXCL12), stimulation of stem cell growth and stem cell mobilization in vivo using low intensity shock wave therapy (Li-ESWT) or regenerative electrical stimulation (RES), are also promising approaches.

Methods: A literature search was performed based on PubMed, Scopus and Google Scholar. The search criteria included original basic science articles, systematic reviews and randomized control trials. All studies were published between 2000 and 2023. Selected, peer-reviewed studies were further analyzed to identify those of relevance. Keywords searched included: "female stress incontinence", "homing factors", "CXCL12", "secretome", "low intensity shockwave therapy" and "regenerative electrical stimulation". The peer-reviewed publications on the key word subjects that contained a novel addition to the existing body of literature were included.

Key content and findings: There is evidence from studies on non-human primates (NHPs) with experimental urinary sphincter injury that CXCL12 can restore sphincter structure and function. Studies with homing factors in human patients with SUI are still to be performed. A large number of clinical studies on the use of secretome or secretome products from mesenchymal stem cells (MSCs) on indications other than human SUI are already available. However, controlled clinical trials on patients with SUI, have to the best of our knowledge, not yet been performed. Also, RES has not been studied in patients with SUI. In contrast, there is clinical evidence that Li-ESWT may improve female SUI.

Conclusions: Treatment with homing factors, MSC secretome/secretome components, Li-ESWT and RES are promising frontiers in the treatment of human SUI caused by sphincter damage.

Post-prostatectomy urinary incontinence (PPUI) is an important issue in the urological practice and imposes a negative effect on quality of life (QoL). Despite recent technological advances, PPUI remains a common complication and the artificial urinary sphincter (AUS) is regarded as the most effective long-term surgical treatment for moderate-to-severe stress urinary incontinence. Success rates for AUS as defined by a continence status of zero to one pad per day range from 59% to 90%. One potential downside of the AUS is the need for periodic revisions in a number of patients. Revision and explantation rates due to mechanical failure, urethral atrophy, infection and erosion vary considerably among studies with reports of 8-45% and 7-17%, respectively. These complications can be classified into different categories, including recurrent or refractory incontinence, erosion and/or infection, and other complications. This review article aims to describe the main AUS-related complications and their management strategies. Diagnostic work-up strategies are explored to facilitate timely identification and management of these complications. Additionally, emerging technologies and future directions in AUS development are discussed, highlighting potential advancements to mitigate complications and enhance device performance. This review consolidates current knowledge and provides insights for clinicians to manage the complexities associated with AUS therapy effectively.