Holmium laser enucleation of the prostate for a case of transition zone prostate cancer.

Standard treatment approaches for localized prostate cancer remain limited to active surveillance, radiotherapy, and radical prostatectomy. We present a case of transition zone prostate cancer that was treated with holmium laser enucleation of the prostate, a procedure that is normally reserved for the management of benign prostatic hyperplasia.

Integration of Patient-Derived Organoids and Organ-on-Chip Systems: Investigating Colorectal Cancer Invasion within the Mechanical and GABAergic Tumor Microenvironment.

Three-dimensional (3D) in vitro models are essential in cancer research, but they often neglect physical forces. In our study, we combined patient-derived tumor organoids with a microfluidic organ-on-chip system to investigate colorectal cancer (CRC) invasion in the tumor microenvironment (TME). This allowed us to create patient-specific tumor models and assess the impact of physical forces on cancer biology. Our findings showed that the organoid-on-chip models more closely resembled patient tumors at the transcriptional level, surpassing organoids alone. Using 'omics' methods and live-cell imaging, we observed heightened responsiveness of KRAS mutant tumors to TME mechanical forces. These tumors also utilized the γ-aminobutyric acid (GABA) neurotransmitter as an energy source, increasing their invasiveness. This bioengineered model holds promise for advancing our understanding of cancer progression and improving CRC treatments.

Synthesis and anti-cancer potential of potent peripheral MAOA inhibitors designed to limit blood:brain penetration.

Monoamine oxidases (MAOA/MAOB) are enzymes known for their role in neurotransmitter regulation in the central nervous system (CNS). Irreversible and non-selective MAO inhibitors (MAOi's) were the first class of antidepressants, thus subsequent work on drugs such as the selective MAOA inhibitor clorgyline has focussed on selectivity and increased CNS penetration. MAOA is highly expressed in high grade and metastatic prostate cancer with a proposed effect on prostate cancer growth, recurrence, and drug resistance. A Phase II Clinical Trial has demonstrated the therapeutic effects of the irreversible nonselective MAOi phenelzine for prostate cancer. However, neurologic adverse effects led to early withdrawal in 25% of the enrolled patient-population. In this work, we revised the clorgyline scaffold with the goal of decreasing CNS penetration to minimize CNS-related side effects while retaining or enhancing MAOA inhibition potency and selectivity. Using the known co-crystal structure of clorgyline bound with FAD co-factor in the hMAOA active site as a reference, we designed and synthesized a series of compounds predicted to have lower CNS penetration (logBB). All synthesized derivatives displayed favorable drug-like characteristics such as predicted Caco-2 permeability and human oral absorption, and exhibited highly selective hMAOA binding interactions. Introduction of an HBD group (NH2 or OH) at position 5 of the phenyl ring clorgyline resulted in 3x more potent hMAOA inhibition with equivalent or better hMAOB selectivity, and similar prostate cancer cell cytotoxicity. In contrast, introduction of larger substituents at this position or at the terminal amine significantly reduced the hMAOA inhibition potency, attributed in part to a steric clash within the binding pocket of the MAOA active site. Replacement of the N-methyl group by a more polar, but larger 2-hydroxyethyl group did not enhance potency. However, introduction of a polar 2-hydroxy in the propyl chain retained the highly selective MAOA inhibition and cancer cell cytotoxicity of clorgyline while reducing its CNS score from 2 to 0. We believe that these results identify a new class of peripherally directed MAOIs that may allow safer therapeutic targeting of MAOA for a variety of anti-cancer and anti-inflammatory indications.

Morphometric Analysis of Prostate Zonal Anatomy After Transurethral Resection of Prostate and Holmium Laser Enucleation of Prostate Using Magnetic Resonance Imaging: A Pilot Study.

OBJECTIVE: The primary purpose was to compare the completeness of adenomectomy and zonal anatomy of prostate on magnetic resonance imaging prostate after transurethral resection of prostate and Holmium enucleation of prostate. The secondary purpose was to investigate the relationship between preoperative total prostate volume and postoperative transition zone and peripheral zone volume after both procedures. MATERIAL AND METHODS: A retrospective review of all patients who underwent transurethral resection of pros- tate or Holmium enucleation of prostate over 3 years (2017-2020) and had at least 1 postoperative magnetic resonance imaging prostate was performed. Volume estimations of the prostate and individual zones were per- formed, and statistical comparisons were made to evaluate morphometric changes between the 2 procedures. RESULTS: A total of 9 patients (mean age, 71.8 years) underwent transurethral resection of prostate and 12 patients (mean age, 66.9 years) underwent Holmium enucleation of prostate. The median pre-operative prostate volume in the Holmium enucleation of prostate group was higher than the transurethral resection of prostate group (101.5 g vs. 62 g; P =.102). However, there was a significant difference in the resected tissue weight favoring Holmium enucleation of prostate over transurethral resection of prostate (P value=.004). The postoperative transition zone and peripheral zone volume as calculated by magnetic resonance imaging remained relatively constant in both procedures. The peripheral zone volume on postoperative magnetic res- onance imaging was found to be independent of transition zone volume even for very large-sized prostates. CONCLUSION: A well-performed transurethral resection of prostate or Holmium enucleation of prostate cannearly completely eliminate the transition zone volume, irrespective of the size of the prostate as confirmed by magnetic resonance imaging prostate. Additionally, the peripheral zone volume is consistent across the entire spectrum of the prostate size.

Bilateral same session flexible ureterorenoscopy for endoscopic management of bilateral renal calculi is noninferior to unilateral flexible ureterorenoscopy for management of multiple unilateral renal calculi: outcomes of a prospective comparative study.

PURPOSE: The aim of the study was to prospectively evaluate safety and efficacy of bilateral same session ureterorenoscopy (BSS-FURS) for management of bilateral renal calculi. METHODS: A prospective comparative study was designed to compare the results of BSS-FURS with unilateral flexible ureterorenoscopy (U-FURS) for management of renal calculi between June 2003 and May 2016. A sample size of 55 patients in each arm was calculated considering a 20% increase in the incidence of complications with BSS-FURS over 15% complication rate in U-FURS (alpha = 0.05; Beta = 0.90). Patient demographics, stone burden, total operative time, postoperative creatinine level, duration of hospital stay, perioperative complications and stone free rate (SFR) were compared in both the groups. The literature pertaining to BSS-FURS was reviewed. RESULTS: Although the study group patients had higher overall stone burden (18.60 ± 7.70 mm vs. 13.32 ± 6.43 mm) and significantly longer operative time (48.30 ± 16.71 min vs. 32.95 ± 13.05 min; p < 0.05) as compared to the control group, the length of hospital stay, SFR (67.85% vs. 78.5%; p = 0.436) and perioperative complications were comparable in both the groups. Most patients who developed postoperative fever from both groups had struvite stones. CONCLUSION: BSS-FURS is a safe and efficient procedure for the management of bilateral renal calculi in the hands of an experienced endourologist. It has comparable SFR and morbidity compared to U-FURS. Caution should be exercised in patients with struvite stones, as they are more likely to develop postoperative fever.

Increase in searches for erectile dysfunction during winter: seasonal variation evidence from Google Trends in the United States.

Several diseases associated with erectile dysfunction (ED), such as type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), are known to have seasonal variation, with increased incidence during winter months. However, no literature exists on whether this chronological-seasonal evolution is also present within ED symptomatology. We hypothesized ED would follow the seasonal pattern of its lifestyle-influenced comorbid conditions and exhibit increased incidence during winter months. In order to investigate the seasonal variation of ED in the United States between 2009 and 2019, Internet search query data were obtained using Google Trends. Normalized search volume was determined during the winter and summer seasons for ED, other diseases known to be significantly associated with ED (T2DM and CAD), kidney stones (positive control), and prostate cancer (negative control). There were significantly more internet search queries for ED during the winter than during the summer (p = 0.001). CAD and T2DM also had significantly increased search volume during winter months compared to summer months (p < 0.001 and p = 0.011, respectively). By contrast, searches for kidney stones were significantly increased in the summer than in the winter (p < 0.001). There was no significant seasonal variation in the relative search frequency for prostate cancer (p = 0.75). In conclusion, Google Trends internet search data across a ten-year period in the United States suggested a seasonal variation in ED, which implies an increase in ED during winter. This novel finding in ED epidemiology may help increase awareness of ED's associated lifestyle risk factors, which may facilitate early medical evaluation and treatment for those at risk of both ED and cardiovascular disease.

Influence of Age and Geography on Chemical Composition of 98043 Urinary Stones from the USA.

BACKGROUND: Urolithiasis is a growing issue globally, but it is heterogeneous, with a different epidemiology and pathophysiology for each different stone composition. OBJECTIVE: The purpose of this study is to describe the incidence of urinary stones in the USA from 2016 to 2019 by chemical composition and to investigate the influence of age and geography on these stone types. DESIGN SETTING AND PARTICIPANTS: We obtained compositional analyses for all urinary stones submitted to a national laboratory over an approximately 3-yr period. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data collected included the chemical constituents of a stone, patient age, and geographical origin. We describe the incidence of each stone type by frequency. Statistical testing was performed to determine the influence of age and geographical region on overall incidence of each stone composition. RESULTS AND LIMITATIONS: In total, 99 908 specimens were analyzed. When pure stones were ordered by frequency, we found that the most common stone type was calcium oxalate (CaOx) (79.2%), followed by uric acid (UA; 14.3%), calcium phosphate (CaPO4; 3.7%), cystine (0.51%), drug induced (0.12%), and magnesium ammonium phosphate (0.04%). CaOx, UA, and CaPO4 were often mixed with one another. Among CaOx stones, the plurality (28.0%) was made of pure calcium oxalate monohydrate (COM), and only 0.002% was pure calcium oxalate dihydrate. There was an overall association between stone composition and both geographical distribution and age (p < 0.001). CONCLUSIONS: CaOx stones comprise the majority of urinary stones in the USA, of which almost 28% were pure COM. Additionally, age and geographical region are significantly associated with variations in stone composition. PATIENT SUMMARY: We evaluated the incidence of urinary stones in the USA based on their chemical composition. The most common stone type was calcium oxalate, the majority of which was pure calcium oxalate monohydrate. We also found age and geographical region to be significantly associated with variations in stone composition.

Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread.

Colorectal cancer (CRC) progression is a complex process that is not well understood. We describe an in vitro organ-on-chip model that emulates in vivo tissue structure and the tumor microenvironment (TME) to better understand intravasation, an early step in metastasis. The CRC-on-chip incorporates fluid flow and peristalsis-like cyclic stretching and consists of endothelial and epithelial compartments, separated by a porous membrane. On-chip imaging and effluent analyses are used to interrogate CRC progression and the resulting cellular heterogeneity. Mass spectrometry-based metabolite profiles are indicative of a CRC disease state. Tumor cells intravasate from the epithelial channel to the endothelial channel, revealing differences in invasion between aggressive and non-aggressive tumor cells. Tuning the TME by peristalsis-like mechanical forces, the epithelial:endothelial interface, and the addition of fibroblasts influences the invasive capabilities of tumor cells. The CRC-on-chip is a tunable human-relevant model system and a valuable tool to study early invasive events in cancer.

Safety and efficacy of holmium laser enucleation of prostate as salvage procedure for persistent or recurrent lower urinary tract symptoms secondary to bladder outlet obstruction after prior prostate artery embolization: a match analysis.

PURPOSE: To evaluate safety and efficacy of Holmium laser enucleation of Prostate (HoLEP) for management of persistent or recurrent lower urinary tract symptoms after prior prostate artery embolization (PAE). We also evaluated histopathological changes in prostate after PAE. METHODS: Ten patients who underwent HoLEP after prior PAE were matched according to age, weight of resected prostate tissue, and anticoagulation status in 1:2 ratio with patients who underwent HoLEP without prior PAE by a researcher who was blinded to patient's outcome at the time of matching. Histopathological examination of prostate tissue was performed to look for changes related to prior PAE. Patient's demographics, perioperative parameters, and follow-up data were retrospectively compared. RESULTS: The median interval between PAE and HoLEP was 25 months [IQR 14.5-37.5]. Patients demographic were comparable in both groups. Intra-operatively plane of enucleation were well-maintained in spite of prior PAE. The differences in duration of surgery, enucleation efficiency, hemoglobin drop, duration of catheterization and hospital stay, and complications were statistically insignificant. Incidental prostate cancer was identified in 10% specimens from both groups. Post-PAE prostate specimens demonstrated evidence of remote-healed infarction represented by dense hyalinized paucicellur connective tissue with surrounding squamous metaplasia. There were no statistically significant differences in AUA symptom scores, maximum urine flow rate, post-void residual urine volume, and PSA at 3- and 6-month follow-up between both groups. CONCLUSIONS: Plane of enucleation is well-maintained after prior PAE. Salvage HoLEP is safe and effective after previous PAE and provide outcome comparable with HoLEP as a primary procedure.

Endourological management of osteitis pubis secondary to a calcified prostate ossifying into the pubic symphysis.

Osteitis pubis is a rare but known complication of multiple urological procedures including transurethral resection of the prostate, prostate cryotherapy, photovaporisation of the prostate, high-intensity focused ultrasound treatment of the prostate, prostatectomy and cystectomy, especially in the context of salvage therapy for prostate cancer. Patients can present with significant often intractable pain secondary to this condition. We report a case of a patient with a history of radiation therapy and salvage cryoablation who presented with osteitis pubis, calcification of the prostatic tissue bed which was inseparable from the pubic symphysis. Treatment with salvage holmium laser enucleation of the prostate and holmium lithotripsy was demonstrated to be effective for palliative management of osteitis pubis from prostatic calcification ossifying into the pubic symphysis.

Salvage Enbloc Thulium Fiber Laser Enucleation of Prostate for Giant Prostatomegaly After Prostatic Urethral Lift.

OBJECTIVE: To demonstrate technique of salvage thylium fiber laser enucleation of prostate in men with history of prior prostatic urethral lift (PUL) implant. PUL is an accepted treatment modality for benign prostatic hyperplasia (BPH) and is currently recommended for surgical management of prostates <80 g in size.1 However, in reality some patients with prostate >80 g also receive PUL.2 A substantial number of these patients may requirement re-treatment for recurrent or persistent lower urinary tract symptoms after PUL.3-5 Patients with larger prostates who fail PUL might be better managed with endoscopic enucleation which is a size-independent modality for treatment of BPH.1,6 Endoscopic enucleation can be accomplished via a variety of energy sources. Thulium fiber laser is a new addition to urologist armamentarium for endoscopic enucleation of prostate. We hereby present a video demonstrating salvage thulium fiber laser enucleation of 198 cc prostate in a men with history of prior PUL. METHODS: A 66-year-old male presented with a history of recurrent urine retention after prior PUL done 2 years prior at an outside institution. Pre-operative international prostate symptom score was 13, maximum uroflow rate was 6.1 ml/sec, residual urine was 26 ml despite maximal medical management. MRI demonstrated a 198 g prostate and PSA was 13.4 ng/dl with negative prostate biopsy. After a detailed discussion of options, he elected endoscopic enucleation. We employed a 550-micron Soltive superpulsed laser fiber set at 2 J and 30 Hz to perform en-bloc enucleation of prostate, and morcellation was performed with the VersaCut Morcellator. We edited the video to demonstrate the technical nuances of this procedure. RESULTS: Surgery was uneventful with enucleation time of 70 minutes and morcellation time of 142 minutes. Implants encountered during enucleation were easily separated with the thulium fiber laser. No attempt was made to remove implants segments extending beyond the plane of enucleation. Morcellation was challenging, with evidence of damage to morcellation probes requiring replacement of 3 morcellator probes. The patient was discharged on post-operative day one after successful voiding trial. At six-week follow up, his international prostate symptom score of 3 with maximum urinary flow rate of 50 mL/sec. He reported no urinary incontinence and his pathology demonstrated BPH. CONCLUSION: This video demonstrates the feasibility of thulium fiber laser enucleation of prostate after PUL, however the findings need to be reproduced in cohort studies. It also demonstrates difficulties encountered during morcellation. For smaller prostates, vaporization may be preferable, thereby avoiding difficulties associated with morcellation.

Nephropleural fistula after supracostal approach for PCNL: report of two cases with review of literature.

Nephropleural fistula is a rarely encountered complication of percutaneous nephrolithotomy (PCNL). Only 11 cases have been reported in literature to date. Often associated with supracostal punctures, the presentation is frequently delayed. Diagnosis is based on imaging, mainly X-rays and CT along with retrograde pyelography that establishes the fistulous connection. A difficult to diagnose condition, any patient with a supracostal access PCNL who presents with delayed symptoms of breathlessness and has leucocytosis with fluid in the lungs on chest imaging should be suspected to have a nephropleural fistula. The management involves intercostal tube thoracostomy to relieve symptoms and drainage of the operated kidney by double-J stent placement, if not placed already. Prompt recognition and management results in excellent recovery with no sequelae. We present our experience with two such cases and our aim was to familiarise the practising urologist regarding the diagnosis and management of this infrequent condition.

Endourological management of multiple large bladder calculi over eroded mesh in an adult with augmented bladder and catheterisable continent appendicovesicostomy.

Migration of abdominal wall mesh in an augmented bladder is a rarely encountered complication leading to formation of bladder stones causing recurrent urinary tract symptoms. The usual management of this condition involves either open surgical or a percutaneous approach for removal of the stone and migrated portion of mesh. Diagnosis of a migrated mesh is usually made intraoperatively during cystolitholapaxy. Appropriate management results in symptomatic improvement. Endoscopic management through catheterisable continent appendicovesicostomy has not been described to manage this challenging condition. To the best of our knowledge, we describe herewith the first report of endoscopic management of a large bladder stone formed over migrated mesh which involved removal of migrated mesh with holmium laser via a Mitrafanoff.

A prospective evaluation of high- and low-power holmium laser settings for transurethral lithotripsy in the management of adults with large bladder calculi.

PURPOSE: To prospectively investigate the efficacy and safety of high-power (100 W) vs low-power (20 W) laser settings for transurethral laser lithotripsy in the management large vesical calculi (> 4 cm). METHODS: All patients with vesical calculi > 4 cm in the maximum dimension and scheduled for transurethral holmium laser lithotripsy were invited to participate in the study. Every alternate patient was treated with either the low- or high-power laser settings. We used a continuous irrigation resectoscope with laser bridge or a laser working element (Karl Storz) for laser lithotripsy of bladder stones. We compared the operative time, intra-operative/post-operative complications (up to 1 year), and stone-free rates between the treatment groups using IBM SPSS Statistics 24 software. Comparisons between treatment groups for continuous variables were assessed using the Welch test, while categorical variables were compared with either the Chi-square or Fisher's exact test. A p value < 0.05 was considered statistically significant. RESULTS: Twenty patients with ten in each cohort were recruited. Preoperative data and mean bladder stone size were comparable in both groups. The duration of surgery was significantly reduced from 70.80 ± 25.28 min in low-power cohort to 40.90 ± 15.01 min in the high-power group (p = 0.005). There were no significant intra-operative complications in either group. All patients were stone-free following the procedure. CONCLUSION: High-power laser setting of up to 100 W results in a significant reduction in duration of surgery without any increase in the complication rate for treatment of large bladder stones.

A randomized controlled trial comparing high and medium power settings for holmium laser enucleation of prostate.

PURPOSE: To report the results of a randomized controlled trial comparing outcomes between medium power (MP) and high power (HP) laser settings for HoLEPs. METHODS: The primary objective was to compare the enucleation efficiency (EE) of HP- HoLEP (80-100 W) with MP-HoLEP (50 - 60 W). The secondary objectives were to compare treatment efficacy and safety between both groups. To show a 25% difference in EE, a sample size of 45 individuals per treatment arm was required (alpha = 0.05; Beta = 0.80). Patients demographic and perioperative factors were analyzed, including EE, hemoglobin drop, duration of catheterization, and length of hospital stay. The surgical outcome was evaluated with AUA symptom score, maximum flow rate, postvoid residual urine, and complications to assess differences between MP and HP HoLEP at baseline, 3 months, 1, and 5 years. Quantitative outcomes were compared with independent sample t tests (2-tailed) and qualitative outcomes were compared with chi-square tests. RESULTS: Preoperative data with the exception of indication for surgery were comparable in both treatment arms. There was no statistically significant difference in enucleation efficiency between the HP-HoLEP and MP-HoLEP laser setting (0.97 ± 0.47 vs. 0.85 ± 0.47 gm/min, p = 0.209). MP laser settings did not increase perioperative or postoperative complications and resulted in durable outcome comparable with HP laser settings at 5-year follow-up. CONCLUSIONS: MP-HoLEP is safe and efficient and does not compromise the outcome for HoLEPs when compared with HP-HoLEP.

Impact of perioperative factors on nadir serum prostate-specific antigen levels after holmium laser enucleation of prostate.

Objective: To investigate the relationship of preoperative prostate size, urinary retention, positive urine culture, and histopathological evidence of prostatitis or incidental prostate cancer on baseline and 3-month nadir prostate-specific antigen (PSA) value after Holmium laser enucleation of prostate (HoLEP). Patients and methods: Data from 90 patients who underwent a HoLEP by En-bloc technique were analyzed. PSA values at baseline and at 3-month follow-up, preoperative urinary retention and urine culture status, weight of resected tissue, and histopathological evidence of prostatitis or prostate cancer were recorded. We performed univariable and multivariable gamma-regression analyses to determine the impact of the aforementioned perioperative variables on preoperative PSA, 3-month postoperative PSA, and change in PSA. Results: Serum PSA reduced significantly at 3 months from 6.3 ± 5.9 ng/mL to 0.6 ± 0.6 ng/mL. On both univariable and multivariable analysis, 3-month nadir level was independent of all preoperative factors examined, except preoperative urinary retention status. Although patients with smaller prostate (resected tissue weight <40 g) had less percentile reduction in PSA when compared with those with larger prostate (resected tissue weight >80 g) (77.67% vs 89.06%; P < .001), patients from both these groups noted a similar PSA nadir level after 3 months (0.54 vs 0.56 ng/dL). The drop in PSA level after HoLEP remained stable up to 1-year follow-up. Conclusions: PSA nadir 3 months after HoLEP remains relatively consistent across patients, regardless of preoperative prostate size, PSA value, urine culture status, and histopathological evidence of prostatitis or incidental prostate cancer.

Holmium Laser Enucleation of Prostate Within 6 Weeks of Transrectal Ultrasound Guided Prostate Biopsy is Safe and Effective.

OBJECTIVE: To evaluate the safety and efficacy of performing Holmium laser enucleation of the prostate (HoLEP) for the treatment of bladder outlet obstruction secondary to an enlarged prostate within 6-weeks of a transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS: We performed a retrospective review of patients who underwent a HoLEP at our institution, excluding any patients with a confounding urologic history and compared patients who underwent a TRUS-guided 6- or 12-core prostate biopsy, and then underwent a HoLEP within 6 weeks (study group) with all other patients (control group). Our primary outcomes were enucleation efficiency (EE) and perioperative complication rate. Our secondary outcomes included postoperative drop in hemoglobin, duration of catheterization, length of hospital stay, voiding metrics at 1 and 6 months and rate of incidental prostate cancer diagnosed on histopathological examination of prostate specimens after HoLEP. To test for differences between the study and control groups, we performed independent sample t-test (2-tailed) and chi-square tests for quantitative and qualitative variables, respectively. P values of < 0.05 were considered statistically significant. RESULTS: 552 patients met inclusion criteria and 84 patients underwent prostate biopsy within a period of 45 days prior to HoLEP. Enucleation efficiency was higher in the study group (P = 0.00). There was no significant difference between the 2 groups regarding perioperative complications, postoperative voiding outcomes, or rate of incidental prostate cancer detection. CONCLUSIONS: TRUS prostate biopsy performed within 6 weeks of HoLEP does not negatively impact operative difficulty or treatment outcome.

Durability of Digital Flexible Ureteroscope in University Hospital and Ambulatory Surgical Center: Is It Time to Rethink?

Introduction and Objectives: Published literature on damages to a digital flexible ureteroscope (DFU) examines a limited number of ureteroscopes and shows wide variation in its durability. The aim of this study was to compare the primary damage location, causes of DFU damages, and the durability of Karl Storz Flex-Xc digital ureteroscope between University Hospital (UH) and Ambulatory Care Surgery Center (ASC). We also evaluated the available literature on the durability of DFU. Methods: Each damaged DFU prospectively underwent a manufacturer's evaluation to determine the reason for return and primary site of damage. Hospital data on the number of ureteroscopic procedures and damaged DFUs over 3 years were retrospectively reviewed. The possible reason for the damage was classified as either intraoperative or between the procedures. The durability of DFUs, type, and cause of damage were compared between the UH and nonteaching ASC. A chi-square test was utilized for categorical variables. When cell frequencies were <5, Fisher's exact test was used. Results: During the study period, 1211 ureteroscopies were performed and 143 ureteroscopes were returned to the manufacturer. The mean number of uses was 7.45 at the UH and 16.5 at the ASC. The location and cause of damage were similar at both locations. The most common locations of primary damage were at the angle cover (70.6%) and instrument channel (19.2%). Most damage occurred during the handling of the ureteroscopes between surgical procedures (78%). On review of the literature, we found that DFUs were 6 times more durable in a nonteaching hospital. Conclusions: The DFU was more than two times as durable in the ASC as in the UH. Most incidents occurred during handling between surgical procedures. Future research is needed to examine the impact of training and certification of support staff on durability of DFUs.

Simultaneous Holmium Laser Enucleation of Prostate with Removal of the Permanent Prostatic Urethral Stent Using the High-Power Holmium Laser: Technique in Two Cases and Review of the Literature.

Background: Although the prostatic urethral stents are no longer used in the United States for treatment of prostatomegaly, urologists will encounter patients with complications of previously placed permanent prostatic stents. We report two cases of persistent bothersome lower urinary tract symptoms (LUTS) after prostatic stent placement treated with simultaneous holmium laser enucleation of prostate (HoLEP) with endoscopic removal of the prostatic urethral stent using high-power holmium laser. We also reviewed the literature regarding the removal of prostatic stents with holmium laser combined with surgical management of benign prostatic hyperplasia. Case Presentation: A 71-year-old man who presented with LUTS, recurrent gross hematuria, and urinary infection, which developed after placement of a prostatic stent 10 years prior for urinary retention secondary to prostatomegaly (80 g). He underwent combined HoLEP with endoscopic removal of the prostatic stent using 100 W holmium laser at a power setting of 2 J and 30 Hz. The surgical steps comprised fragmentation of the stent in situ by making incisions at 5, 7, and 12 o'clock positions followed by enucleation of the prostate. The stent was then separated from enucleated tissue in the urinary bladder. The remaining prostate adenoma was then morcellated and removed. The patient remained asymptomatic at 10-year follow-up. Another patient was 62-year-old man who developed recurrence of bothersome LUTS, 1 year after placement a prostatic stent for urinary retention. On investigation his prostate was 105 g and stent showed partial migration in the bladder with overlying calcification. HoLEP and stent removal was performed in a manner similar to the first patient. This patient also remained asymptomatic at a 1-year follow-up. Conclusion: Combined HoLEP with removal of a prostatic urethral stent using a high-power holmium laser is safe and effective with long-term durable outcome.

Pharmacokinetic properties of the temozolomide perillyl alcohol conjugate (NEO212) in mice.

BACKGROUND: NEO212 is a novel small-molecule anticancer agent that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH) to the alkylating agent temozolomide (TMZ). It is undergoing preclinical development as a therapeutic for brain-localized malignancies. The aim of this study was to characterize metabolism and pharmacokinetic (PK) properties of NEO212 in preclinical models. METHODS: We used mass spectrometry (MS) and modified high-performance liquid chromatography to identify and quantitate NEO212 and its metabolites in cultured glioblastoma cells, in mouse plasma, brain, and excreta after oral gavage. RESULTS: Our methods allowed identification and quantitation of NEO212, POH, TMZ, as well as primary metabolites 5-aminoimidazole-4-carboxamide (AIC) and perillic acid (PA). Intracellular concentrations of TMZ were greater after treatment of U251TR cells with NEO212 than after treatment with TMZ. The half-life of NEO212 in mouse plasma was 94 min. In mice harboring syngeneic GL261 brain tumors, the amount of NEO212 was greater in the tumor-bearing hemisphere than in the contralateral normal hemisphere. The brain:plasma ratio of NEO212 was greater than that of TMZ. Excretion of unaltered NEO212 was through feces, whereas its AIC metabolite was excreted via urine. CONCLUSIONS: NEO212 preferentially concentrates in brain tumor tissue over normal brain tissue, and compared to TMZ has a higher brain:plasma ratio, altogether revealing favorable features to encourage its further development as a brain-targeted therapeutic. Its breakdown into well-characterized, long-lived metabolites, in particular AIC and PA, will provide useful equivalents for PK studies during further drug development and clinical trials with NEO212.