Hundred years of transperineal prostate biopsy.

The earliest recorded efforts to biopsy prostate, in the early 20th century, were made through transperineal (TP) approach, with open perineal prostate biopsy (PBx) being considered the gold standard for prostate cancer (PCa) diagnosis in that era. Later, to minimize morbidity and increase diagnostic accuracy, several technical modifications and transrectal ultrasound (TRUS) assistance were incorporated. However, in the 1980s, the transrectal (TR) approach became the predominant PBx method following the introduction of TRUS-TR PBx with sextant sampling, providing a convenient and efficacious method for prostate sampling. With modernization of PCa diagnosis, a recent resurgence of the TP PBx has been observed, driven primarily by TR drawbacks of infectious complications and sampling limitations. TP PBx is rapidly emerging as the new PBx standard, being officially recommended as the initial approach for biopsy in Europe and is increasingly being conducted and studied in the United States. The modern era of TP PBx is based on the improvements in local anesthesia techniques, TP access systems, and robotic assistance. These modifications and advancements have improved the ease of use, patient comfort, and diagnostic outcomes with TP PBx. Herein, we present a history of the evolution of TP PBx spanning over 100 years and explore the basis of the technique that merits future utilization.

Does the type of biopsy used for diagnosis impact subsequent treatment selection in prostate cancer patients?

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) targeted biopsy has emerged as an augmentation to systematic prostate biopsy (SBx) with improved diagnostic accuracy. The purpose of this study was to determine whether biopsy modality impacted management of prostate cancer (PCa). METHODS: We performed a retrospective review of patients with newly diagnosed non-metastatic PCa at our institution (2014-2020). Either ultrasound-guided 12-core SBx or SBx plus ≥1targeted biopsy cores from identifiable lesions on mpMRI were performed. Patients were managed with active surveillance (AS), radiation therapy (RT), or radical prostatectomy (RP). Multivariate logistic and multinomial regression analyses were performed. RESULTS: Of 578 patients, 221(38%) proceeded with AS, 121(21%) received RT, and 236(41%) underwent RP. Median age and prostate-specific antigen (PSA) were 65.4 years and 7.2 ng/mL, respectively. On multivariate analysis, biopsy type did not predict decision to pursue treatment (p=.951). On multinomial regression analysis, biopsy type did not predict selection of AS over RP (p=.973) or RT over RP (p=.813). Alternatively, age, grade group, and PSA were significant predictors of management selection. CONCLUSIONS: Biopsy technique did not impact management for patients with new PCa diagnosis. Despite paradigm shifts in obtaining tissue diagnosis, age, PSA, and grade group remain valuable indices for shared decision-making and counseling patients with PCa.

The Efficiency of Moses Technology Holmium Laser for Treating Renal Stones During Flexible Ureteroscopy: Relationship Between Stone Volume, Time, and Energy.

Introduction: There are limited data on how stone factors relate to flexible ureteroscopy (f-URS) laser lithotripsy efficiency and outcomes when using the Moses Technology Ho:YAG system. We examined the relationship of stone volume and density to lithotripsy, lasing times, and energy used to treat a single renal stone. We also assessed short-term clinical outcomes. Methods: We analyzed patients undergoing f-URS by a single surgeon using high-power Moses Technology Ho:YAG system (Lumenis). We only included cases with a CT confirming a solitary renal stone. Ureteral stones, staged and bilateral procedures were excluded. Stone dimensions and HU were obtained. Volume (mm3) was calculated using European Association of Urology criteria. Laser energy (J), lithotripsy, and lasing times were obtained. Laser activity was calculated by dividing lasing time by lithotripsy time. Relationships between time, stone density, volume, and energy were assessed using Spearman correlation. Complications were assessed using Clavien-Dindo grade. Residual fragments (RF) were determined on imaging within 3 months. Results: Twenty-nine patients met the inclusion criteria. Mean (range) stone volume and density were 290 mm3 (42-1700) and 814 HU (170-1675), respectively. Mean lithotripsy and lasing times were 11.9 (3.6-26.0) and 6.0 (0.6-19.6) minutes, respectively. Mean laser activity was 47%. Mean fragmentation speed was 0.9 mm3/s. Mean energy used per unit stone volume was 38.2 J/mm3. Time taken to perform fragmentation had a stronger association with the stone volume vs stone density. Three (10.3%) and 2 (6.9%) patients had a Clavien Grade 1 and 2 complications, respectively. At follow-up the zero-fragment rate was 79.3%. Conclusions: When using the Moses Technology laser to ablate a single renal stone with f-URS, the fragmentation speed was ∼1 mm3/s. Stone volume, not density was correlated to lasing time. We propose mm3/s be considered a measure that has implications for technique efficiency and comparing laser platforms.

Burnback: the role of pulse duration and energy on fiber-tip degradation during high-power laser lithotripsy.

High-power holmium lasers have become popular for ureteroscopic laser lithotripsy and dusting. Our aim was to investigate the effect of pulse duration and pulse energy on fiber-tip degradation when using high-power settings for popcorn lithotripsy. BegoStones were fragmented in a glass bulb to simulate renal calyx, using a 120 W Ho:YAG laser. A 242 µm fiber was placed via the ureteroscope 2 mm distance from stones (popcorn model). To assess the effect of pulse duration on fiber-tip degradation, long pulse (LP) and short pulse (SP) settings were compared at settings of 1.0Jx20Hz (20 W), 0.5Jx70Hz (35 W), and 1.0Jx40Hz (40 W). To assess the effect of pulse energy on tip degradation, 40 W SP settings (0.5Jx80Hz, 0.8Jx50Hz, and 1.0Jx40Hz) were tested. Pulse duration was measured using a photodetector and peak power was then calculated using the pulse duration and pulse energy. Experiments were conducted for 4 min. Fiber-tip length was measured before and after using a digital caliper. Fiber-tip degradation was least when using LP for all settings tested (p < 0.01). For 40 W settings, tip degradation was significantly lower when using a pulse energy of 0.5 J compared to 0.8 J or 1.0 J (p < 0.004). LP mode results in less fiber burnback for all power settings tested. Total power is more important than frequency in the development of burnback. However, high-power 40 W settings can be utilized with less burnback if lower pulse energies are used. Understanding these parameters can improve the longevity of the laser fiber and improve procedural efficiency.

Tobacco smoke exposure enhances reward sensitivity in male and female rats.

RATIONALE: Systemic administration of the tobacco smoke constituent nicotine stimulates brain reward function in rats. However, it is unknown if the inhalation of tobacco smoke affects brain reward function. OBJECTIVES: These experiments investigated if exposure to smoke from high-nicotine SPECTRUM research cigarettes increases reward function and affects the rewarding effects of nicotine in adult male and female Wistar rats. METHODS: Reward function after smoke or nicotine exposure was investigated using the intracranial self-stimulation (ICSS) procedure. A decrease in reward thresholds reflects an increase in reward function. In the first experiment, the rats were exposed to tobacco smoke for 40 min/day for 9 days, and the rewarding effects of nicotine (0.03-0.6 mg/kg) were investigated 3 weeks later. In the second experiment, the dose effects of tobacco smoke exposure (40-min sessions, 1-4 cigarettes burnt simultaneously) on reward function were investigated. RESULTS: Tobacco smoke exposure did not affect the nicotine-induced decrease in reward thresholds or response latencies in male and female rats. Smoke exposure lowered the brain reward thresholds to a similar degree in males and females and caused a greater decrease in latencies in females. There was a positive relationship between plasma nicotine and cotinine levels and the nicotine content of the SPECTRUM research cigarettes. Similar smoke exposure conditions led to higher plasma nicotine and cotinine levels in female than male rats. CONCLUSION: These findings indicate that tobacco smoke exposure enhances brain reward function but does not potentiate the rewarding effects of nicotine in male and female rats.

Relationship Between Nicotine Intake and Reward Function in Rats With Intermittent Short Versus Long Access to Nicotine.

INTRODUCTION: Tobacco use improves mood states and smoking cessation leads to anhedonia, which contributes to relapse. Animal studies have shown that noncontingent nicotine administration enhances brain reward function and leads to dependence. However, little is known about the effects of nicotine self-administration on the state of the reward system. METHODS: To investigate the relationship between nicotine self-administration and reward function, rats were prepared with intracranial self-stimulation electrodes and intravenous catheters. The rats were trained on the intracranial self-stimulation procedure and allowed to self-administer 0.03 mg/kg/infusion of nicotine. All rats self-administered nicotine daily for 10 days (1 hour/day) and were then switched to an intermittent short access (ShA, 1 hour/day) or long access (LgA, 23 hour/day) schedule (2 days/week, 5 weeks). RESULTS: During the first 10 daily, 1-hour sessions, nicotine self-administration decreased the reward thresholds, which indicates that nicotine potentiates reward function. After switching to the intermittent LgA or ShA schedule, nicotine intake was lower in the ShA rats than the LgA rats. The LgA rats increased their nicotine intake over time and they gradually consumed a higher percentage of their nicotine during the light phase. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine induced a larger increase in reward thresholds (ie, anhedonia) in the LgA rats than the ShA rats. In the LgA rats, nAChR blockade with mecamylamine decreased nicotine intake for 2 hours and this was followed by a rebound increase in nicotine intake. CONCLUSIONS: A brief period of nicotine self-administration enhances reward function and a high level of nicotine intake leads to dependence. IMPLICATIONS: These animal studies indicate that there is a strong relationship between the level of nicotine intake and brain reward function. A high level of nicotine intake was more rewarding than a low level of nicotine intake and nicotine dependence was observed after long, but not short, access to nicotine. This powerful combination of nicotine reward and withdrawal makes it difficult to quit smoking. Blockade of nAChRs temporarily decreased nicotine intake, but this was followed by a large rebound increase in nicotine intake. Therefore, nAChR blockade might not decrease the use of combustible cigarettes or electronic cigarettes.

Recent Updates in Animal Models of Nicotine Withdrawal: Intracranial Self-Stimulation and Somatic Signs.

Tobacco use is one of the leading causes of disease, disability, and death in the world. Despite the negative health consequences of smoking and the fact that most people would like to quit, very few people are able to maintain abstinence. Nicotine, the main psychoactive component of tobacco, is mildly rewarding and plays a role in the initiation and maintenance of smoking. Cessation of nicotine intake induces mild somatic withdrawal symptoms that may contribute to the maintenance of smoking. However, it has been hypothesized that negative affective nicotine withdrawal signs are of greater motivational significance in contributing to relapse and continued smoking (Markou and Koob (eds) Intracranial self-stimulation thresholds as a measure of reward, vol 2. Oxford University Press, New York, 1993; Koob et al., Semin Neurosci 5:351-358, 1993). Intracranial self-stimulation (ICSS) has been established as a method to assess the acute rewarding properties of nicotine and the dysphoria associated with nicotine withdrawal. The ICSS method provides a means to measure the negative affective aspects of nicotine withdrawal in animal models and may contribute to the understanding of the neurobiological bases of nicotine dependence.

Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone.

Among cathinone drugs known as bath salts, methylenedioxypyrovalerone (MDPV) exerts its potent actions via the dopamine (DA) system, and at intoxicating doses may produce adverse behavioral effects. Previous work by our group suggests that prolonged alterations in correlated neural activity between cortical and striatal areas could underlie, at least in part, the adverse reactions to this bath salt drug. In the present study, we assessed the effect of acute MDPV administration on brain functional connectivity at 1 and 24 h in rats. Using graph theory metrics to assess in vivo brain functional network organization we observed that 24 h after MDPV administration there was an increased clustering coefficient, rich club index, and average path length. Increases in these metrics suggests that MDPV produces a prolonged pattern of correlated activity characterized by greater interactions between subsets of high degree nodes but a reduced interaction with regions outside this core subset. Further analysis revealed that the core set of nodes include prefrontal cortical, amygdala, hypothalamic, somatosensory and striatal areas. At the molecular level, MDPV downregulated the dopamine transporter (DAT) in striatum and produced a shift in its subcellular distribution, an effect likely to involve rapid internalization at the membrane. These new findings suggest that potent binding of MDPV to DAT may trigger internalization and a prolonged alteration in homeostatic regulation of DA and functional brain network reorganization. We propose that the observed MDPV-induced network reorganization and DAergic changes may contribute to previously reported adverse behavioral responses to MDPV.