En Bloc Resection of Bladder Tumors (ERBT) using different lasers - Hybrid and Holmium Laser

ABSTRACT Introduction: The En-bloc Resection of Bladder Tumors (ERBT) is a method that offers more benefits compared to the traditional Transurethral Resection of Bladder Tumor (TURBT) (1, 2). Recent studies have shown that ERBT offers better pathological analysis and oncological outcomes (3-6). Thulium and holmium are the most frequently used lasers for this procedure, with the hybrid laser being a new addition that combines thulium and diode to improve hemostatic properties (5, 7-9). Objective: This report aims to discuss the use of two types of lasers, hybrid and holmium, for ERBT. Material and Methods: Two case studies were conducted. The first case featured a 68-year-old male with two tumors measuring 1.5cm and 2cm. The hybrid laser was used for the procedure. The second case involved a 70-year-old female with a 5cm tumor on the posterior bladder wall, and holmium laser was used with morcellation of the tumor. The quality of histopathological analysis was evaluated. The perioperative data and the entire procedure of the two cases were documented in a step-by-step video. Results: Both lasers demonstrated excellent results without technical difficulties. There was no bleeding, and both patients were discharged with one day of hospitalization. The detrusor muscle was present without artifacts, and the morcellation did not affect the analysis. The first case showed a pT1G3, and the second case showed a pT2 urothelial carcinoma. The hybrid laser exhibited superior hemostatic capacity compared to the holmium laser. Conclusion: ERBT can use hybrid or holmium lasers without affecting histopathological analysis, even with morcellation.

En Bloc Resection of Bladder Tumors (ERBT) using different lasers - Hybrid and Holmium Laser.

INTRODUCTION: The En-bloc Resection of Bladder Tumors (ERBT) is a method that offers more benefits compared to the traditional Transurethral Resection of Bladder Tumor (TURBT) (1, 2). Recent studies have shown that ERBT offers better pathological analysis and oncological outcomes (3-6). Thulium and holmium are the most frequently used lasers for this procedure, with the hybrid laser being a new addition that combines thulium and diode to improve hemostatic properties (5, 7-9). OBJECTIVE: This report aims to discuss the use of two types of lasers, hybrid and holmium, for ERBT. MATERIAL AND METHODS: Two case studies were conducted. The first case featured a 68-year-old male with two tumors measuring 1.5cm and 2cm. The hybrid laser was used for the procedure. The second case involved a 70-year-old female with a 5cm tumor on the posterior bladder wall, and holmium laser was used with morcellation of the tumor. The quality of histopathological analysis was evaluated. The perioperative data and the entire procedure of the two cases were documented in a step-by-step video. RESULTS: Both lasers demonstrated excellent results without technical difficulties. There was no bleeding, and both patients were discharged with one day of hospitalization. The detrusor muscle was present without artifacts, and the morcellation did not affect the analysis. The first case showed a pT1G3, and the second case showed a pT2 urothelial carcinoma. The hybrid laser exhibited superior hemostatic capacity compared to the holmium laser. CONCLUSION: ERBT can use hybrid or holmium lasers without affecting histopathological analysis, even with morcellation.

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.

Robot-Assisted Pyeloureterostomy in the Treatment of the Lower Pole Ureteropelvic Junction Obstruction in an Incomplete Duplicated System.

PURPOSE: To describe the surgical treatment of a patient harboring a ureteropelvic junction obstruction in the lower unit of an incomplete duplicated collecting system. METHODS: A female patient with 32-year old presented a progressively increasing left lumbar pain for 1 year and urinary tract infections for the past 10 years. Computed tomography demonstrated a ureteropelvic junction obstruction in the lower unit of an incomplete duplicated urinary collecting system. RESULTS: The patient underwent a robot-assisted pyeloureterostomy. The surgical time was 118 minutes and there was no intraoperative complication. During surgery, anomalous vessels crossing to the lower pole of the kidney were identified. The bladder catheter and abdominal drain were removed at the first- and second postoperative days. The length of the hospital stay was 2 days and the postoperative course was uneventful. The double-J stent was retrieved 4 weeks after surgery. At 18 months of follow-up, the patient had complete pain resolution and no new episodes of urinary tract infections. The control image exam revealed minimal residual hydronephrosis. CONCLUSION: Robot-assisted pyeloureterostomy was an effective approach to the present case. Many times, the surgical strategy for patients with anatomic variants is determined intra-operatively. The surgeon must have a wide range of skills and be prepared for a timely decision.

Holmium Laser Enucleation of the Prostate Simulation: Analysis of Realism and Level of Difficulty by Holmium Laser Enucleation of the Prostate-naïve Urologists.

OBJECTIVE: To evaluate the opinion of Holmium laser enucleation of the prostate (HoLEP)-naïve urologists about a surgical simulator and the level of difficulty at each step. MATERIALS AND METHODS: We evaluated 40 HoLEP-naïve urologists in a course involving 4 steps: lecture introducing Holmium laser basics and technique; live surgery; video explaining prostate enucleation using simulators; and simulator trial. A survey was applied to evaluate content validity and face validity of the simulator. Subjects also ranked the level of difficulty of each surgical step. RESULTS: All urologists agreed on the importance of a validated HoLEP simulator in training; 95% agreed that simulation-based training is essential for patient safety. The mean rate of face validity of all analyzed components was 8.4 (8.1-9.0). Instrumentation was considered the most realistic component, followed by laser-tissue interaction. Positioning the fiber and bladder neck incisions (BNIs) at 5 and 7-o'clock were the easiest steps. Detaching the median lobe from the bladder neck, BNI at 12, dividing the mucosal bridge distally, and joining the upper and lower incisions were the most difficult steps. Residents found more difficulty in joining the BNIs distally (3.6 vs 2.4, P = .006) and in dividing the mucosal bridge distally (4.0 vs 3.0, P = .038) when compared to specialists. CONCLUSION: HoLEP-naïve urologists found this simulator useful and important for patient safety. Most components were considered realistic. Simulation was able to reproduce the levels of difficulty usually found in real life cases. The level of expertise may influence the learning process of some steps.

The role of bladder diverticula in the prevalence of acute urinary retention in patients with BPH who are candidates to surgery

ABSTRACT Introduction: The urinary bladder diverticula (BD) secondary to benign prostatic hyperplasia (BPH) is a complication that can lead to urinary stasis, stone, urinary tract infection (UTI) and tumors. It's role in acute urinary retention (AUR) is not totally understood. Objectives: To determine the effect of BD size on AUR rates in patients with BPH candidates to surgery. Subjects and Methods: We performed a retrospective cohort study of 47 patients with BPH and BD who underwent BPH surgery associated to complete bladder diverticulectomy from 2006 to 2016. We analyzed risk factors for AUR in patients with BD using univariate, multivariate and correlation analysis. Results: There was a difference in the size of the diverticula, with 6.8 cm vs. 4.5 cm among patients with and without AUR respectively (p=0.005). The ROC curve showed a correlation between the size of BD and the risk of AUR. The value of 5.15 cm presented a sensitivity of 73% and a specificity of 72%. The area under the curve was 0.75 (p=0.01). Comparing groups with BD >5.0 cm vs. ≤5.0 cm, the AUR incidence was 74% and 27.8% respectively with an OR of 2.65 (1.20-5.85) (p=0.005). In the multivariate analysis, only the size of the diverticula reached statistical significance (p=0.012). Conclusions: The diameter of BD is an independent risk factor for AUR in patients with BPH and BD who are candidates to surgery. A diameter greater than 5.15 cm increases the risk of AUR.

Treating metastatic prostate cancer with microRNA-145.

Prostate cancer (PCa) is an incurable disease at the metastatic stage. Although there are different options for treatment, the results are limited. MicroRNAs (miRNAs) are a group of small, noncoding, regulatory RNAs with important roles in regulating gene expression. miR-145 is reported to be a key tumor suppressor miRNA (tsmiR) that controls important oncogenes, such as MYC and RAS. In this study, in vitro studies were performed to show the control of MYC and RAS by miR-145. Flow cytometry was used to analyze cell proliferation and apoptosis. The efficacy of miR-145 in treating metastatic PCa was tested in nude mice using a model of bone metastasis promoted by intraventricular injection of PC-3MLuc-C6 cells. Tumor growth was evaluated by an in vivo bioluminescence system. After the full establishment of metastases on day 21, six animals were treated with three intravenous doses of miR-145 (on days 21, 24 and 27), and six were injected with scramble miRNA as controls. Compared to the controls, tumor growth was significantly reduced in animals receiving miR-145, most importantly on day 7 after the third and last dose of miRNA. After discontinuing the treatment, tumor growth resumed, becoming similar to the group of non-treated animals. A decrease in MYC and RAS expression was observed in all cell lines after treatment with miR-145, although statistical significance was achieved only in experiments with LNCaP and PC3 cell lines, with a decrease in 56% (p = 0.012) and 31% (p = 0.013) of RAS expression, respectively. Our results suggest that miR-145 is a potential molecule to be tested for treatment of metastatic, castration-resistant PCa.

The role of bladder diverticula in the prevalence of acute urinary retention in patients with BPH who are candidates to surgery.

INTRODUCTION: The urinary bladder diverticula (BD) secondary to benign prostatic hyperplasia (BPH) is a complication that can lead to urinary stasis, stone, urinary tract infection (UTI) and tumors. It's role in acute urinary retention (AUR) is not totally understood. OBJECTIVES: To determine the effect of BD size on AUR rates in patients with BPH candidates to surgery. SUBJECTS AND METHODS: We performed a retrospective cohort study of 47 patients with BPH and BD who underwent BPH surgery associated to complete bladder diverticulectomy from 2006 to 2016. We analyzed risk factors for AUR in patients with BD using univariate, multivariate and correlation analysis. RESULTS: There was a difference in the size of the diverticula, with 6.8 cm vs. 4.5 cm among patients with and without AUR respectively (p=0.005). The ROC curve showed a correlation between the size of BD and the risk of AUR. The value of 5.15 cm presented a sensitivity of 73% and a specificity of 72%. The area under the curve was 0.75 (p=0.01). Comparing groups with BD >5.0 cm vs. ≤5.0 cm, the AUR incidence was 74% and 27.8% respectively with an OR of 2.65 (1.20-5.85) (p=0.005). In the multivariate analysis, only the size of the diverticula reached statistical significance (p=0.012). CONCLUSIONS: The diameter of BD is an independent risk factor for AUR in patients with BPH and BD who are candidates to surgery. A diameter greater than 5.15 cm increases the risk of AUR.

Role of Genetic Polymorphisms in the Development and Prognosis of Sporadic and Familial Prostate Cancer.

BACKGROUNDS: Our aim was to evaluate the role of 20 genetic polymorphisms in the development and prognosis of sporadic and familial PC. A case-control study of 185 patients who underwent radical prostatectomy from 1997 to 2011. These patients were divided into two groups based on their family history. Gleason grade, PSA value and pathological TNM 2002 stage were used as prognostic factors. Blood samples from 70 men without PC were used as controls. The SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. RESULTS: Considering susceptibility, the polymorphic allele in the SNP rs2660753 on chromosome 3 was significantly more prevalent in controls (p = 0.01). For familial clustering, the polymorphic homozygote genotype of the SNP rs7931342 was five times more frequent in patients with familial PC compared to sporadic PC (p = 0.01). Regarding the SNP 1447295, the polymorphic homozygote genotype was more prevalent in patients with organ-confined PC (p = 0.05), and most importantly, the polymorphic allele occurred more frequently in patients without biochemical recurrence (p = 0.01). Kaplan-Meier analysis showed a median biochemical recurrence free survival of 124.2 compared to 85.6 months for patients with the wild-type allele (p = 0.007). CONCLUSION: Our findings provide the evidence for the association of 20 recently highlighted SNPs and their susceptibility, familial clustering, staging, Gleason score and biochemical recurrence of PC. We believe that the association between these SNPs and PC may contribute to the development of alternative tools that can facilitate the early detection and prognosis of this disease.

Nanoradiopharmaceuticals for breast cancer imaging: development, characterization, and imaging in inducted animals.

Monoclonal antibodies as polymeric nanoparticles are quite interesting and endow this new drug category with many advantages, especially by reducing the number of adverse reactions and, in the case of radiopharmaceuticals, also reducing the amount of radiation (dose) administered to the patient. In this study, a nanoradiopharmaceutical was developed using polylactic acid (PLA)/polyvinyl alcohol (PVA)/montmorillonite (MMT)/trastuzumab nanoparticles labeled with technetium-99m (99mTc) for breast cancer imaging. In order to confirm the nanoparticle formation, atomic force microscopy and dynamic light scattering were performed. Cytotoxicity of the nanoparticle and biodistribution with 99mTc in healthy and inducted animals were also measured. The results from atomic force microscopy showed that the nanoparticles were spherical, with a size range of ~200-500 nm. The dynamic light scattering analysis demonstrated that over 90% of the nanoparticles produced had a size of 287 nm with a zeta potential of -14,6 mV. The cytotoxicity results demonstrated that the nanoparticles were capable of reaching breast cancer cells. The biodistribution data demonstrated that the PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal clearance and also a high uptake by the lesion, as ~45% of the PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as nanoradiopharmaceuticals for breast cancer imaging.

Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis.

PURPOSE: To compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia. METHODS: We prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL). RESULTS: All groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q max), both of which were significantly better in the TURP group, and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q max. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q max and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria. CONCLUSIONS: TURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.

Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer

Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.

The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior.

BACKGROUND: The molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. METHODS: The expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. RESULTS: MiR-371 underexpression correlated with non-organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5α-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5α-dihydrotestosterone. CONCLUSION: Our data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.

Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radiopharmaceuticals for many years; however, their use as nanoradiopharmaceuticals is very innovative and creates a new way to establish radiopharmacy in this new scenario offered by nanotechnology. In this study we developed and tested nano-MDP-labelled with 99mTc in rats induced with bone cancer metastasis and the results showed that it may work in patients. However, some further experiments are required in order to initiate protocols in humans.

Can we predict which patients will experience resolution of detrusor overactivity after transurethral resection of the prostate?

PURPOSE: We determined which clinical and urodynamic variables may be related to persistent detrusor overactivity after transurethral resection of the prostate. MATERIALS AND METHODS: We studied 46 patients with bladder outlet obstruction due to benign prostatic hyperplasia who were treated with transurethral prostate resection from 2011 to 2012. All patients underwent urodynamic analysis preoperatively and 12 months postoperatively. Clinical and urodynamic variables in the preoperative period were correlated with the resolution of detrusor overactivity postoperatively. RESULTS: Patients with detrusor overactivity in the preoperative period were older (65.2 vs 61.1 years, p = 0.041) and had a higher I-PSS (International Prostate Symptom Score) (25.2 vs 19, p = 0.014) and higher maximum flow rate (8.6 vs 6.6 ml per second, p = 0.039). Patients with persistent detrusor overactivity were statistically older than those with resolution (69 vs 63 years, p = 0.043). Detrusor overactivity persisted in 63.6% of patients with maximum cystometric capacity less than 250 ml compared to 20% of those with greater than 250 ml (p = 0.024). When analyzing urodynamic variables together, we found a 66.7% chance of persistent detrusor overactivity in patients with maximum cystometric capacity less than 250 ml and detrusor overactivity amplitude greater than 40 cm H2O (p = 0.041). When these characteristics were associated with early detrusor overactivity, the chance of persistent detrusor overactivity was 83.3% (p = 0.013). CONCLUSIONS: Advanced patient age together with low maximum cystometric capacity, and early and high detrusor overactivity amplitude are the most important predictors of persistent detrusor overactivity after relief of bladder outlet obstruction.

Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer.

INTRODUCTION AND OBJECTIVE: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). MATERIALS AND METHODS: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. RESULTS: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. CONCLUSION: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.