Flexible Ureteroscopic Guided Laparoscopic Ureteroplasty For The Treatment Of Ureteral Stricture.

INTRODUCTION: Ureteral stricture is often a consequence of urolithiasis or previous endourological procedures (1-3). Precisely delineating the stricture zone intraoperatively is crucial to minimize ureter shortening and target only the affected tissue (4, 5). Flexible ureteroscopy offers a significant advantage in this regard. OBJECTIVE: This video aims to demonstrate the step-by-step technique of flexible ureteroscopic guided laparoscopic ureteroplasty for treating ureteral stricture caused by urolithiasis and prior endourological interventions. PATIENT AND METHODS: We present a case of a 36-year-old male with a history of urolithiasis and unsuccessful endourological treatments, including endoureterotomy and balloon dilation, diagnosed with re-stenosis of the proximal ureter of 1 cm through ureteroscopy and pyelography. He underwent a successful laparoscopic ureteroplasty. While the lead surgeon performed the laparoscopy, an assistant conducted the flexible ureteroscopy. Intraoperatively, using transillumination facilitated by the flexible ureteroscope, we can precisely identify the narrowed area, allowing for resection of only the damaged segment. Subsequently, we perform the end-to-end ureteroplasty, confirming its patency through the seamless passage of the ureteroscope. Upon completion, we employ a fat patch to safeguard the anastomosis. RESULTS: The patient was discharged on the third postoperative day. Double J stent was removed six weeks after surgery. Symptoms resolved. Renal function improved: eGFR 49 to 67 ml/min. Furthermore, improvement was observed in the DTPA scan, and a decrease in hydronephrosis was noted on the follow-up tomography. CONCLUSION: Flexible ureteroscopy effectively identifies the stricture zone in laparoscopic ureteroplasty, enhancing surgical precision and outcomes. This approach is safe, effective, and reproducible, offering a valuable technique in the surgical treatment of ureteral strictures.

Honing the Hunt: A Comprehensive Review of Cell-free Tumor DNA to Predict Neoadjuvant Therapy Efficacy in Bladder Cancer.

OBJECTIVE: To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer. METHODS: A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool. RESULTS: In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy. CONCLUSION: Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors.

Play it safe: renal function after bilateral flexible ureteroscopy for kidney stones.

PURPOSE: We searched for perioperative renal function deterioration risk factors in patients that underwent bilateral flexible ureteroscopy (fURS) for kidney stones. METHODS: From August 2016 to February 2020, symptomatic patients > 18 years old with bilateral kidney stones up to 20 mm in each side were prospectively studied. Serum creatinine samples were collected on admission to surgery, immediate postoperative (IPO), on POD 3, 10, and 30. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) without a race coefficient. RESULTS: Thirty patients underwent bilateral fURS. Comparing to preoperative eGFR, median IPO and POD3 eGFR (p < 0.001) were significantly lower, and POD10 (p = 0.092) and POD30 (p = 0.648) were similar to preoperative eGFR. During follow-up, 22/30 (73.3%), 14/30 (46.7%), and 7/30 (23.3%) of the patients presented a decrease > 10% eGFR, > 20% eGFR, and > 30% eGFR, respectively. Multivariate analysis demonstrated that lower preoperative eGFR is a risk factor for eGFR < 60 mL/min/1.73 m2, p = 0.019 [1.021-1.263; 1.136]; ASA > 1 is a risk factor for decrease of eGFR > 10%, p = 0.028 [1.25-51.13; 8.00]; longer operative time is a risk factor for decrease of eGFR > 20%, p = 0.042 [1.00-1.05; 1.028]; and operative time ≥ 120 min is a risk factor for decrease of eGFR > 30%, p = 0.026 [0.016-0.773; 0.113]. CONCLUSIONS: Renal function suffers a reversible decrease after bilateral fURS. Our study suggests that adequate selection of patients and maintaining operative time < 120 min are relevant factors in preventing acute renal function deterioration following bilateral fURS.

Intraoperative computed tomography for detection of residual stones in endourology procedures: systematic review and meta-analysis.

BACKGROUND: Success rates in endourological procedures, notably percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS), have demonstrated suboptimal outcomes, leading to more reinterventions and radiation exposure. Recently, the use of intraoperative computed tomography (ICT) scans has been hypothesized as a promising solution for improving outcomes in endourology procedures. With this considered, we conducted a comprehensive systematic review and meta-analysis encompassing all available studies that evaluate the impact of the use of intraoperative CT scans on surgical outcomes compared to conventional fluoroscopic-guided procedures. METHODS: This systematic review was conducted in accordance with PRISMA guidelines. Multiple databases were systematically searched up to December of 2023. This study aimed to directly compare the use of an ICT scan with the standard non-ICT-guided procedure. The primary endpoint of interest was success rate, and the secondary endpoints were complications and reintervention rates, while radiation exposure was also evaluated. Data extraction and quality assessment were performed following Cochrane recommendations. Data was presented as an Odds ratio with 95%CI across trials and a random-effects model was selected for pooling of data. RESULTS: A comprehensive search yielded 533 studies, resulting in the selection of 3 cohorts including 327 patients (103 ICT vs 224 in non-ICT). Primary outcome was significantly higher in the experimental group versus the control group (84.5% vs 41.4% respectively, 307 patients; 95% CI [3.61, 12.72]; p<0.00001; I2=0). Reintervention rates also decreased from 32.6% in the control to 12.6% in the ICT group (OR 0.34; 95%CI [0.12,0.94]; p =0.04; I2= 48%), whereas complication rates did not exhibit significant differences. Radiation exposure was also significantly reduced in two of the included studies. CONCLUSION: This meta-analysis highlights a favorable outcome with intraoperative CT scan use in PCNL procedures, showing a considerable increase in SFR when compared to standard fluoroscopy and nephroscopy. Despite limited studies, our synthesis underscores the potential of ICT scans to significantly reduce residual stones and their consequences for endourology patients, as reinterventions and follow-up ionizing radiation studies.

The Effect of Gene Editing by CRISPR-Cas9 of miR-21 and the Indirect Target MMP9 in Metastatic Prostate Cancer.

Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.

Laparoscopic Ureterocalicostomy Technique

ABSTRACT Purpose: Ureterocalicostomy is a technique that was first described by Neuwirt in 1948 (1) The laparoscopic access was initiated in 2003 by Cherullo et al. (2), following the established principles of open surgery. In 2004, Gill et al. had two patients with UPJO treated with laparoscopic ureterocalicostomy, with success (3). In 2014, Arap et. al. presented a case series with good results in adults and children in our service (4). There are factors that prepare the surgeon for an ureterocalicostomy, such as the renal cortex thickness, although the decision is mainly taken during the procedure (5). Material and Methods: A 24 years-old female patient with right lumbar pain was referred to our institution. She already had a right open pyeloplasty two years ago. The CT scan presented a right hydronephrotic kidney, DMSA scan with 30% of relative function and a DTPA scan with an obstructive pattern. Results: A laparoscopic ureterocalicostomy was performed due to the intra-operative findings (inferior kidney pole thickness and challenging access to the uretero-pelvic junction). The overall time was 130 minutes with no complications. The patient was discharged in two days and the double J was withdrawn in four weeks. The CT scan within one year demonstrates a reduction of the hydronephrosis. She had no more lumbar pain. Conclusion: In complex cases, the laparoscopic ureterocalicostomy proves to be a safe and efficient procedure, with a free tension-free anastomosis and the advantages of the laparoscopic access.

Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model.

BACKGROUND: Previously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia. METHODS AND RESULTS: In vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 µg/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation. CONCLUSION: Our results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6.

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer.

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 µg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Laparoscopic Ureterocalicostomy Technique.

PURPOSE: Ureterocalicostomy is a technique that was first described by Neuwirt in 1948 (1) The laparoscopic access was initiated in 2003 by Cherullo et al. (2), following the established principles of open surgery. In 2004, Gill et al. had two patients with UPJO treated with laparoscopic ureterocalicostomy, with success (3). In 2014, Arap et. al. presented a case series with good results in adults and children in our service (4). There are factors that prepare the surgeon for an ureterocalicostomy, such as the renal cortex thickness, although the decision is mainly taken during the procedure (5). MATERIAL AND METHODS: A 24 years-old female patient with right lumbar pain was referred to our institution. She already had a right open pyeloplasty two years ago. The CT scan presented a right hydronephrotic kidney, DMSA scan with 30% of relative function and a DTPA scan with an obstructive pattern. RESULTS: A laparoscopic ureterocalicostomy was performed due to the intra-operative findings (inferior kidney pole thickness and challenging access to the uretero-pelvic junction). The overall time was 130 minutes with no complications. The patient was discharged in two days and the double J was withdrawn in four weeks. The CT scan within one year demonstrates a reduction of the hydronephrosis. She had no more lumbar pain. CONCLUSION: In complex cases, the laparoscopic ureterocalicostomy proves to be a safe and efficient procedure, with a free tension-free anastomosis and the advantages of the laparoscopic access.

The Distensibility of the Human Vena Cava and Its Importance to In Vitro Studies of Venous Compression Syndromes: A Search for a Suitable Polymer for 3-Dimensional Printing.

BACKGROUND: Venous compression syndromes are clinical conditions in which the large veins are compressed by other anatomical structures. Laboratory simulations may help us better understand the hemodynamics in venous compressions by creating situations similar to those seen in vivo. The aim of this study is to produce a model of the caval bifurcation using a polymer with distensibility similar to the human vena cava. METHODS: Fragments of the inferior vena cava were collected from 13 deceased kidney donors (aged 15-37 years) and were tested for deformation (strain) when subjected to distension at 50 N/cm2. Strips of 5 different polymers-thermic polyurethane and Agilus30 with Vero Magenta (AV) (in 3 different hardnesses) and silicone-were subjected to the same biomechanical tests and compared with the vena cava. A model of the caval bifurcation was produced with 3-D printing. RESULTS: The deformation (strain) of the vena cava wall was 0.16 ± 0.9 when submitted to stress close to 50 N/cm2. Silicone showed a strain higher than the standard deviation of venous fragments. The strain of AV resin 95 Shore was lower than the standard deviation of the venous fragments. AV Resins 70 and 85 Shore showed strains within the standard deviation of the venous specimen, with 70 Shore being closest to the mean venous strain. Therefore, this material was selected for modeling the caval bifurcation. The computed tomography scan image generated a computer model of the caval bifurcation and was printed in 3 dimensions. In addition, the segments of 2 adjacent vertebrae were also printed to reference the compression site. CONCLUSIONS: The 3-D printing of large veins can produce models with anatomy and biomechanics similar to those of human veins and opens a field of investigation into the hemodynamics of venous compression syndromes. Polymers with Shore A70 appear to have biomechanical properties similar to those of the vena cava wall. The model obtained in this study can be used in several in vitro studies of May-Thurner Syndrome.

Perioperative Morbidity of Radical Prostatectomy After Intensive Neoadjuvant Androgen Blockade in Men With High-Risk Prostate Cancer: Results of Phase II Trial Compared to a Control Group.

INTRODUCTION: Recent studies about intense neoadjuvant therapy followed by Radical Prostatectomy (RP) lack standardized criteria regarding surgical complications and comparison to a group of patients who underwent RP without the use of neoadjuvant therapy. The aim of this study is to describe and compare the perioperative complication rates. MATERIALS AND METHODS: This was a prospective, single-center phase II trial in patients with high-risk prostate cancer (HRPCa). The control group included HRPCa patients who underwent RP outside the clinical trial during the same study recruitment period. The interventional group was randomized (1:1) to receive neoadjuvant androgen deprivation therapy plus abiraterone with or without apalutamide followed by RP. Complications observed up to 30 days of surgery were classified based on the Clavien-Dindo classification. Uni- and multivariate analyses were carried out to assess predictive factors associated with perioperative complications. RESULTS: In total, 124 patients with HRPCa were underwent to RP between May 27, 2019 and August 6, 2021, including 61 patients in the intervention group and 63 patients in the control group. The general and major complications in the intervention group reached 29.6% and 6.6%, respectively, and 39.7% and 7.9% in the control group, respectively. There was no significant difference between groups. We observed 4.9% of thromboembolic event in the neoadjuvant group. CONCLUSIONS: There was no significant increase in morbidity rate in RP after intense neoadjuvant therapy. The association of intense androgen deprivation neoadjuvant therapy with RP and extended pelvic lymphadenectomy may increase the risk of a perioperative thromboembolic events.

Imaging Signs of May-Thurner Syndrome in Asymptomatic Patients: Computed Tomography Angiography Analysis of Kidney Donors.

BACKGROUND: The current study aimed to evaluate the distance between the right common iliac artery (RCIA) and lumbar vertebra in asymptomatic patients in order to determine whether such distance was statistically correlated with the left common iliac vein (LCIV) diameter (LCIVD) and to investigate if both measures were related to demographic characteristics and anthropometric data, such as sex, age, height, and body mass index (BMI). METHODS: In this descriptive and uncontrolled anatomic study, data from high-definition computed tomography (CT) angiography images of living kidney donors without a medical history of chronic venous insufficiency or past deep vein thrombosis (DVT) were analyzed. The RCIA crossed over the LCIV in 311 individuals, who were then included in this study. CT scans were reviewed to measure (1) the narrowest space between the RCIA and fifth lumbar vertebral body and (2) the LCIVD. Measures were subjected to normality tests and were divided according to the sex of the study population. Correlations of measures with age, BMI, and height were calculated. RESULTS: Of the 311 patients analyzed, 66.6% (n = 207) were female. The mean lumbar vertebral body-iliac artery distance (LVBIAD) was 7.2 mm, whereas the mean LCIVD was 8.5 mm; both were higher in men (P < 0.001). The statistical analysis of LVBIAD and LCIVD distributions revealed no normality pattern (P < 0.05). The analysis of the correlation between them showed a weak statistically significant relationship with age. A linear regression model considering the normality percentile interval indicated a strong positive correlation between LVBIAD and LCIVD (R2 = 0.884). CONCLUSIONS: The LVBIAD was <5 mm and <3 mm in 25% and 5% of asymptomatic individuals, respectively. The LCIVD correlated with the space between the RCIA and lumbar vertebra. The distance between the RCIA and lumbar vertebra and the LCIVD were higher in male subjects and older patients, but did not correlate with BMI and height.

Cholesterol Triggers Nuclear Co-Association of Androgen Receptor, p160 Steroid Coactivators, and p300/CBP-Associated Factor Leading to Androgenic Axis Transactivation in Castration-Resistant Prostate Cancer.

BACKGROUND/AIMS: Cholesterol modulates intratumoral androgenic signaling in prostate cancer; however, the molecular mechanisms underlying these changes in castration-resistant prostate cancer (CRPC) are not fully elucidated. Herein, we investigated the effect of cholesterol on androgen receptor (AR) coactivators expression and tumorigenesis in vitro and in vivo. METHODS: Herein, we monitored the expression of AR coactivators (SRC-1, 2, 3 and PCAF) genes in PC-3 cells exposed to 2µg/mL of cholesterol for 8 hours by qPCR. We also performed cell migration at 0, 8, 24, 48 and 72h and flow cytometry assays (viability, apoptosis, and cell cycle) after a 24h exposure. Immunofluorescence assay was performed to evaluate the protein expression of the AR coactivators. Additionally, in vivo experiments were conducted using 22 male NOD/SCID mice. Mice were fed a standard (Control) or hypercholesterolemic (HCOL) diet for 21 days and then subcutaneously implanted with PC-3 cells. The tumor volume was calculated every two days, and after four weeks, the tumors were resected, weighed, and the serum lipid profile was measured. We also measured the intratumoral lipid profile and AR coactivators gene and protein expression by qPCR and Western Blot, respectively. Intratumor testosterone and dihydrotestosterone (DHT) concentrations were determined using ELISA. RESULTS: Cholesterol up-regulated the gene expression of coactivators SRC-1, SRC-2, SRC-3and PCAF, increasing AR expression in PC-3 cells. Next, cholesterol-supplemented PC-3 cells exhibited increased cell migration and altered cell cycle phases, leading to changes in proliferation and reduced apoptosis. We found that SRC-1, SRC-2, SRC-3 and PCAF proteins co-localized in the nucleus of cholesterol-supplemented cells and co-associate with AR. In the in vivo model, the hypercholesterolemic (HCOL) group displayed higher serum total and intratumoral cholesterol levels, increased testosterone and dihydrotestosterone concentrations, and up-regulated AR coactivator expression. The tumor volume of the HCOL group was significantly higher than the control group. CONCLUSION: Our findings revealed that increased nuclear translocation of the coactivators leads to up-regulated AR gene and protein expression, potentially influencing tumor progression. Studies targeting cholesterol-modulated changes in AR coactivator expression may provide insights into the molecular mechanisms associated with the CRPC phenotype.

Effectiveness of Intrarectal Povidone-iodine Cleansing Plus Formalin Disinfection of the Needle Tip in Decreasing Infectious Complications After Transrectal Prostate Biopsy: A Randomized Controlled Trial.

PURPOSE: Prostate biopsy is mostly performed through the transrectal route worldwide and infectious complications may occur in up to 7% of cases. Therefore, alternative strategies to decrease infectious complications are needed. Our aim was to evaluate the effectiveness of intrarectal povidone-iodine cleansing plus formalin disinfection of the needle tip in decreasing infectious complications after transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: We conducted a prospective, single-center, phase III trial in patients undergoing transrectal ultrasound guided prostate biopsy randomized 1:1 to rectal mucosa cleansing with gauze soaked in 10% povidone-iodine solution wrapped around the gloved index finger and needle tip disinfection by immersion in a 10% formalin solution before each puncture vs control group. The primary end point was the rate of infectious complications defined as 1 or more of the following events: fever, urinary tract infection, or sepsis. RESULTS: Overall, 633 patients were randomized to the intervention group and 623 to the control group. The infectious complication rate was 3.9% in the intervention group and 6.4% in the control group (RR 0.61; 95% CI 0.36-0.99; P = .049). The rates of sepsis, urinary tract infection, and fever were 0.3% vs 0.5% (P = .646), 2.3% vs 4.1% (P = .071), and 1.3% vs 1.9% (P = .443), respectively. The positive urine culture rate was 5.2% in the intervention group and 9% in the control group (RR 0.57; P = .015). There was no statistically significant difference between the groups regarding the occurrence of noninfectious adverse events. CONCLUSIONS: Intrarectal povidone-iodine cleansing plus formalin disinfection of the biopsy needle tip was associated with a reduction in infectious complications after transrectal prostate biopsy.

miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma.

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA-miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA-miRNA regulation during disease progression.

Holmium Laser Resection of Large Bladder Tumors: Technique Description, Feasibility, and Histopathological Quality Analysis.

BACKGROUND: The HoLERBT (Holmium Laser En-bloc Resection of Bladder Tumors) has emerged as an alternative to classical TURBT (Transurethral Resection of Bladder Tumor). Recent randomized trial and meta-analysis corroborate with the benefits in pathological analysis, perioperative and long-term oncological outcomes.1-3 However, the treatment of large tumors and the technique of extraction from the bladder is a problem to be overcome.1,4 OBJECTIVE: To describe the laser resection of bladder tumors and demonstrate the feasibility of this procedure even for large tumors throughout a series of cases. It is also discussed the quality of the histopathological analysis. METHODS: A series of 8 cases randomized selected to be the pilot for a trial comparing TURBT and HoLERBT in large tumors (>3 cm) in progress was analyzed (Brazilian Registry of Clinical Trials number RBR-67npwrk). The perioperative data and 1-year outcomes were assessed and the quality of histopathological analysis after morcellation was evaluated in terms of histopathology, grade, and stage. The entire procedure of one case is shown in a step-by-step video. RESULTS: The mean follow-up was 12.6 months. The mean age was 59.6 (42-85) years, and the mean tumor size was 4.7 (4-8) cm. All the resections were En-bloc. There were 2 cases of NMIBC, 4 cases of MIBC, 1 paraganglioma, and 1 adenocarcinoma. The histopathological analysis confirmed the presence of detrusor muscle layer and accurate diagnosis and staging in all cases (100%). There were no perioperative Clavien-Dindo > 1 complications, no blood transfusion, and no bladder perforations. The histopathology analysis reveals excellent quality without artifacts of fulguration. CONCLUSION: The holmium laser resection followed by morcellation of large bladder tumors is a feasible procedure. No complications occurred in our series of cases and all cases provided excellent material for histopathological analysis.

Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study.

Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines. Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia. Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group. Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery. Institutional protocol number: Animal Ethics Committee 1332/2019.

A Prospective, Randomized Trial Comparing the Outcomes of Open vs Laparoscopic Partial Nephrectomy.

PURPOSE: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking. MATERIALS AND METHODS: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results. RESULTS: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006). CONCLUSIONS: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.

Grafting Area Reduction in Peyronie's Disease Surgery: Comparative Assessment Between Double Y Vs iGrafter APP Using 3D-Printed Penile Models.

BACKGROUND: The use of plaque incision and graft techniques (PIG) for the treatment of severe Peyronie's disease (PD), may lead to erectile dysfunction (ED); graft size is 1 of the contributing factors for post-PIG ED. Recently the iGrafter software APP was introduced using a mathematical algorithm to distribute the incisions along the penile length resulting in a smaller grafting area. AIM: Compare 2 PIG techniques, the Double-Y(DY) and iGrafter, in 3 main aspects: (i) Total grafting area; (ii) The variation in calculating the grafting to be used; (iii) time to perform the PIG. METHODS: Six urologists with expertise in sexual medicine performed both techniques twice using four 3-D validated training models for PD with a standard 60° uniplanar dorsal curvature. OUTCOMES: The graft areas and operative partial and total time for each step of the operation were recorded for each procedure. Unpaired t-test and the coefficient of variation for graft area across surgeons was calculated comparing both techniques. RESULTS: For all surgeons, the use of iGrafter resulted in 2 grafts, for the DY technique in 1 graft. Overall, TT for the iGrafter was significantly longer than for DY technique (49.4 ± 11 vs 40.7 ± 5.7 minute; P = .02), The iGrafter grafting area was significantly smaller (11.6 ± 1.2 vs 23.3 ± 5.4 cm2; P: .01), representing a 50.2% area reduction when compared to the DY. The variation of graft area, using the iGrafter also yielded a more consistent graft across all surgeons (CV = 10.56% vs 23.28%). CLINICAL SIGNIFICANCE: The iGrafter, when compared to DY technique, reduced the graft area by 50%, which potentially means less erectile dysfunction. STRENGTHS AND LIMITATIONS: Our study eliminates anatomical variations found in a real clinical case making it possible to compare surgical techniques with the same penile anatomy. However, the 3D-printed model cannot replicate the living human tissue property preventing a simulation close to actual surgery. CONCLUSION: The use of the iGrafter software for PIG surgery has shown to be a promising technique for severe PD management resulting in smaller graft size (about 50% smaller when compared to the DY), although it might be more time-consuming. Tourchi A, Nascimento B, de Freita Miranda A, et al. Grafting Area Reduction in Peyronie's Disease Surgery: Comparative Assessment Between Double Y Vs iGrafter APP Using 3D-Printed Penile Models. J Sex Med 2022;19:669-675.