Diagnostic value of [99mTc]Tc-PSMA-I&S-SPECT/CT for the primary staging and restaging of prostate cancer.

Background: A large number of studies have proved that prostate-specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) provides excellent accuracy in primary staging and restaging of prostate cancer. Less data exist with PSMA-single photon emission computed tomography (SPECT)/CT investigations. Objective: The aim of this study was to evaluate the performance of [99mTc]Tc-PSMA-I&S (for imaging and surgery) in prostate cancer. Design and methods: We retrospectively analysed PSMA-SPECT/CT scans of 20 healthy volunteers and 100 male patients with prostate cancer. All of them had histologically confirmed prostate cancer. In all, 28 patients were examined for primary staging and 72 for biochemical recurrence or progressive disease. Whole body SPECT/CT imaging was carried out 6 h after the intravenous administration of 666 ± 102 MBq [99mTc]Tc-PSMA-I&S. Images were evaluated visually and semi-quantitatively. Results: Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy for primary prostate cancer were 86%, 100%, 100%, 83% and 92%, respectively. For detecting metastases in primary staging, these values were 88%, 100%, 100%, 85% and 93%, respectively. The radiopharmaceutical uptake of primary prostate cancer was significantly higher than in normal prostate. The patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the method in the visualization of local recurrence were 67%, 100%, 100%, 86% and 89%, and for detecting metastases in restaging were 91%, 92%, 98%, 75% and 91%, respectively. In restaging, detection rates were 37% under prostate-specific antigen level of 1 ng/mL, 74% between 1 and 5 ng/mL and 80% >5 ng/mL. Conclusion: [99mTc]Tc-PSMA-I&S-SPECT/CT can be easily integrated into the routine diagnostic practice, and it provides usable data in primary staging and restaging of prostate cancer. Quantitative assessment of PSMA-SPECT/CT has the potential to be used to differentiate between physiological and pathological intraprostatic tracer uptake.

Penile melanoma: a pathological report of two cases.

BACKGROUND: Penile melanoma (PM) is a rare tumor, accounting for less than 2% of all penile cancers. PM can occur on the surface of the glans, foreskin, and opening of the urethra. Furthermore, PM primarily affects older individuals and is not associated with sun exposure. Currently, there is no specific staging system for genitourinary tract melanomas, so these tumors are typically staged using the criteria for cutaneous melanoma. Limited data in the literature suggests that PM generally has a poor clinical prognosis. CASE PRESENTATION: Here, we describe two cases of PM. The first case affected a 62-year-old male who presented with hematuria and a painful tumor in the distal urethra, leading to a suspicion of penile cancer. The second case involved a 68-year-old male who noticed a rapidly evolving dark spot on his foreskin. Histological analysis confirmed the presence of melanoma in both patients. The tumors showed a diffuse and strong PRAME-positivity and lacked BRAF mutation in both cases. Additionally, the second tumor harbored an activating CKIT mutation. An enhanced PD-L1 expression was observed in both tumors. CONCLUSIONS: We presented two rare forms of mucosal melanoma and highlighted the entities in the differential diagnosis. Based on our experience PRAME is a helpful marker for making the diagnosis of PM, and PD-L1 can predict the success of the immunotherapy. We also emphasize the need for an organ-specific staging system for PMs.

Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience.

Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging. Aim: The integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease. Patients and methods: The data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration. Results: From 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07-0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described. Conclusion: PSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT.

Effects of intraoperative positive end-expiratory pressure optimization on respiratory mechanics and the inflammatory response: a randomized controlled trial.

Applying lung protective mechanical ventilation (LPV) during general anaesthesia even in patients with non-injured lungs is recommended. However, the effects of an individual PEEP-optimisation on respiratory mechanics, oxygenation and their potential correlation with the inflammatory response and postoperative complications have not been evaluated have not been compared to standard LPV in patients undergoing major abdominal surgery. Thirty-nine patients undergoing open radical cystectomy were enrolled in this study. In the study group (SG) optimal PEEP was determined by a decremental titration procedure and defined as the PEEP value resulting the highest static pulmonary compliance. In the control group (CG) PEEP was set to 6 cmH2O. Primary endpoints were intraoperative respiratory mechanics and gas exchange parameters. Secondary outcomes were perioperative procalcitonin kinetics and postoperative pulmonary complications. Optimal PEEP levels (median = 10, range: 8-14 cmH2O), PaO2/FiO2 (451.24 ± 121.78 mmHg vs. 404.15 ± 115.87 mmHg, P = 0.005) and static pulmonary compliance (52.54 ± 13.59 ml cmH2O-1 vs. 45.22 ± 9.13 ml cmH2O-1, P < 0.0001) were significantly higher, while driving pressure (8.26 ± 1.74 cmH2O vs. 9.73 ± 4.02 cmH2O, P < 0.0001) was significantly lower in the SG as compared to the CG. No significant intergroup differences were found in procalcitonin kinetics (P = 0.076). Composite outcome results indicated a non-significant reduction of postoperative complications in the SG. Intraoperative PEEP-optimization resulted in significant improvement in gas exchange and pulmonary mechanics as compared to standard LPV. Whether these have any effect on short and long term outcomes require further investigations. Trial registration: Clinicaltrials.gov, identifier: NCT02931409.

Clinicopathological Findings on 28 Cases with XP11.2 Renal Cell Carcinoma.

Xp11.2 translocation carcinoma is a distinct subtype of renal cell carcinoma characterized by translocations involving the TFE3 gene. Our study included the morphological, immunohistochemical and clinicopathological examination of 28 Xp11.2 RCCs. The immunophenotype has been assessed by using CA9, CK7, CD10, AMACR, MelanA, HMB45, Cathepsin K and TFE3 immunostainings. The diagnosis was confirmed by TFE3 break-apart FISH in 25 cases. The ages of 13 male and 15 female patients, without underlying renal disease or having undergone chemotherapy ranged from 8 to 72. The mean size of the tumors was 78.5 mm. Forty-three percent of patients were diagnosed in the pT3/pT4 stage with distant metastasis in 6 cases. Histological appearance was branching-papillary composed of clear cells with voluminous cytoplasm in 13 and variable in 15 cases, including one tumor with anaplastic carcinoma and another with rhabdoid morphology. Three tumors were labeled with CA9, while CK7 was negative in all cases. Diffuse CD10 reaction was observed in 17 tumors and diffuse AMACR positivity was described in 14 tumors. The expression of melanocytic markers and Cathepsin K were seen only in 7 and 6 cases, respectively. TFE3 immunohistochemistry displayed a positive reaction in 26/28 samples. TFE3 rearrangement was detected in all the analyzed cases (25/25), including one with the loss of the entire labeled break-point region. The follow-up time ranged from 2 to 300 months, with 7 cancer-related deaths. In summary, Xp11.2 carcinoma is an uncommon form of renal cell carcinoma with a variable histomorphology and rather aggressive clinical course.

Prospective observational study to evaluate the persistence of treatment with denosumab in patients with bone metastases from solid tumors in routine clinical practice: final analysis.

PURPOSE: In the integrated analysis of phase III head-to-head trials in patients with advanced solid tumors, denosumab demonstrated superiority over zoledronic acid in preventing skeletal-related events (SREs). Regular and continued drug use (persistence) is a precondition of clinical efficacy; persistence in real-life is yet undetermined for denosumab. METHODS: This was a single-arm, prospective, observational, non-interventional study in 598 patients with bone metastases from breast, prostate, lung, or other solid tumors treated with denosumab every four weeks in real-world clinical practice in Austria, Czech Republic, Hungary, Slovakia, and Bulgaria. Persistence was defined as denosumab administration at ≤ 35-day intervals over 24 or 48 weeks, respectively. RESULTS: Previous SREs were found in 10.9% of patients. 62.6% were persistent over 24 weeks and 40.1% over 48 weeks. The Kaplan-Meier median (95% CI) time to non-persistence was 274.0 days (232.0, 316.0). The most frequent reason for non-persistence was delayed administration. There was a trend towards weaker analgesics over time, with approximately 60% of patients not requiring any analgesics. Serum calcium remained within the normal range throughout the study. Adjudicated osteonecrosis of the jaw was documented in three patients with an incidence per patient-year (95% CI) of 0.012 (0.004, 0.029). CONCLUSIONS: Most patients received denosumab regularly once every four weeks over 24 weeks of treatment. Non-persistence was mainly due to delayed administration. The incidence of adverse drug reactions, especially of osteonecrosis of the jaw, was in line with expectations from previous studies.

Renal Cell Carcinoma with Clear Cell Papillary Features: Perspectives of a Differential Diagnosis.

Thirty-one cases of low-grade renal cell carcinoma (RCC) with clear cells and tubulopapillary/papillary architecture were analyzed retrospectively with immunohistochemical and genetic markers to gain more experience with the differential diagnosis of such cases. All samples coexpressed CK7 and CA9; the TFE3 or TFEB reactions were negative; the CD10 and the AMACR stainings were negative in 27 cases and 30 cases, respectively. The FISH assays for papillary RCC, available in 27 cases, and deletion of chromosome 3p, available in 29 cases, gave negative results. The results for 3p deletion, VHL gene mutation or VHL gene promoter region hypermethylation testing, along with the diffuse CD10-positivity in 2 cases confirmed 21 cases as clear cell papillary RCC (CCPRCC; CK7+, CA9+; no 3p loss, no VHL abnormality) and 10 cases as clear cell RCC (CCRCC; CK7+, CA9+; no 3p loss, VHL abnormality mutation/hypermethylation present). In CCPRCCs, the representative growth pattern was branching tubulo-acinar, commonly accompanied by cyst formation. The linear nuclear arrangement or cup-shaped staining of CA9 did not necessarily indicate CCPRCC, and the absence of these did not exclude the diagnosis of CCPPRC. One tumor infiltrated the renal sinus; the others exhibited pT1 stage; and metastatic outcome was not recorded. The CCRCC cases were in pT1 stage; 6 exhibited cup-shaped staining of CA9, and 1 displayed lymph node metastasis at the time of surgery. Distant metastatic disease was not observed. In summary, the VHL abnormalities distinguished the subset of CCRCC with diffuse CK7-positivity and no 3p loss from cases of CCPRCC.

Papaverine hydrochloride containing nanostructured lyotropic liquid crystal formulation as a potential drug delivery system for the treatment of erectile dysfunction.

PURPOSE: Papaverine hydrochloride (PaHCl) is an old, well-known drug with spasmolytic activity but it has therapeutic effect in erectile dysfunction, too. As an intracavernous injection, it is not used in urologic clinics today because the side effects of the injection are pain, scarring or priapism. Our aim was to develop and test a topical semi-solid preparation containing PaHCl that would provide an alternative administration option by eliminating the undesirable side effects of the injection. MATERIALS AND METHODS: Lyotropic liquid crystal (LLC) systems were formulated as a semi-solid preparation with different concentrations of PaHCl. The characterization of the LLC structure was performed by polarization microscopy using a Leica image analyzer and rheological measurements. The drug diffusion and penetration tests were performed with in vitro synthetic membrane and an ex vivo human epidermis, using Franz diffusion cell to test the skin penetration of PaHCl. Human skin was investigated by Raman microscope to visualize the Active Pharmaceutical Ingredient (API) in different skin layers. RESULTS: The results of diffusion and penetration showed reverse concentration dependency. The in vitro and ex vivo studies correlated with each other and the results of Raman microscopy. The LLC structure influenced the penetration results, the lower viscosity and lamellar structure increased penetration through the skin. CONCLUSION: Based on our results, a PaHCl containing topically used LLC formulation may be a suitable and effective alternative to the injectable formulation.

[Edifications and modern strategies of localized prostate cancers' definitive therapy]. / Prosztatarákban szenvedo betegek definitív ellátásának tanulságai és modern stratégiái.

INTRODUCTION: Mortality of prostate carcinoma can be significantly decreased by the use of modern diagnostic and therapeutic options. Patients in early stages can be cured by radical surgery or radiotherapy. AIM: Overview and comparison of previous and present diagnostic and therapeutic methods regarding accuracy of diagnosis, improvement of efficiency and decrease of toxicities. We also aimed to explore general correlations in case of serious complications. METHOD: By the help of two prostate cancer patients we demonstrate the importance of accuracy and change of histological diagnosis, significance of proper imaging techniques, and also show parameters of conventional and modern radiotherapy and their acute and chronic complications. Differences of previous and present methods and their consequences were analyzed. RESULTS: By now, histological findings in the patients' diagnosis have changed. Both patients received conventional three-dimensional definitive radiotherapy in 2009-2011, and their prostate cancer was cured. In one case, urinary bladder also received radiotherapy because prostate carcinoma had infiltrated it. In the other case, the contemporary radiotherapy involved urinary bladder's fundus due to safety margins. Although acute grade 2 cystitis developed in both cases and recovered in several weeks, as late complication bladder shrinkage developed, which after the ineffectiveness of conventional therapies had to be cured by radical cystoprostatectomy - in order to cease bleeding and to cure incontinence. CONCLUSIONS: In case of prostate carcinomas, serious complications can be avoided by the improvement of diagnostic and therapeutic options. Synthesis of data could be more successful if they were analyzed in the light of previous experiences. Orv Hetil. 2018; 159(32): 1317-1325.

[Initial experiences with 99mTc-PSMA-SPECT/CT in patients with prostate cancer]. / Kezdeti tapasztalatok a 99mTc-PSMA-SPECT/CT-vel prosztatarákos betegekben.

INTRODUCTION: The prostate-specific membrane antigen (PSMA) is a transmembrane protein, that is highly expressed on the surface of prostate cancer cells. In the last few years, several PSMA-specific ligands have been developed, that can be successfully used to detect primary prostate cancer, tumor recurrences and metastases as well. AIM: The goal of our work was to examine the clinical application of a 99mtechnetium-labeled PSMA-radiopharmaceutical as part of the routine diagnostics of prostate cancer. METHOD: We examined 15 male patients with verified prostate adenocarcinoma with suspicion of progression or recurrence of the disease. We performed whole-body PSMA-SPECT/CTs and multiparametric MRIs of the prostate and the pelvic regions within a week. We used 99mTc-mas3-y-nal-k(Sub-KuE) for the PSMA-SPECT scans. The images were visually evaluated by independent observers. The results were compared with the follow-up bone scintigraphies as well. RESULTS: Twenty-two PSMA-positive lesions were found. Nine of them were localized outside, 13 were within the MRI's field of view. From these 13 lesions, 7 matched with the SPECT/CT results and in 5 cases the MRI images showed no abnormalities. In one case, bone metastasis was suspected on the MRI scan but there was no corresponding pathological tracer uptake on the SPECT images. In two patients, none of the examinations showed signs of prostate malignancy. Four patients had PSMA-positive bone metastases. One of them had a matching PSMA/SPECT and bone scintigraphy result and in one case the PSMA examination showed metastasis in contrast to the negative bone scintigraphy. CONCLUSION: PSMA-SPECT/CT with 99mTc-mas3-y-nal-k(Sub-KuE) is a promising diagnostic tool. This technique is capable of visualizing bone metastases and it can detect local recurrences and visceral metastases as well. Orv Hetil. 2018; 159(35): 1433-1440.

Does anchoring vaginal mesh increase the potential for correcting stress incontinence?

BACKGROUND: This study aims to explore the feasibility of anchoring a four-arm transvaginal mesh (TVM) to the mid-urethra to correct an anterior compartment POP-Quantification stage II-III (Q II-III) and concomitant genuine SUI. METHODS: We analysed clinical data from 248 patients with stage II-III anterior prolapse and concomitant SUI who had undergone surgery at a tertiary referral centre in Hungary between January 2008 and June 2010. One hundred and twenty-four women treated with anterior colporrhaphy and 62 patients implanted with a conventional permanent TVM were selected as historical matched controls. Sixty-two patients received a modified permanent TVM, where the mesh was fixed to the mid-urethra with two stitches for the purpose of potentially correcting SUI. Surgical complications were classified using the Clavien-Dindo (CD) classification system. RESULTS: The anti-SUI efficacy was minimally higher in the mTVM group than in the original TVM group (p = 0.44, 96.8% vs 91.9%, respectively), while prosthesis surgery was more effective than anterior colporrhaphy in improving the anterior compartment POP-Q status (96.8, 90.3% vs 64.5%, respectively). Anchoring the mesh did not increase the extrusion rate (p = 0.11). The de novo urge symptoms were not more prevalent among those who had received additional periurethral stitches (p = 1.00, 11.3% vs 12.9%). The incidence of reoperation observed in the mTVM group was non-significantly lower than that in the TVM group (p = 0.15, 6.5% vs 16.1%); however, the difference did not reach the level of significance. The early postoperative complication profile was more favourable among the mTVM patients (classified as CD I: 8.1%; CD II: 1.6%; and CD IIIb: 1.6%) as compared to the TVM group (p = 0.013). CONCLUSIONS: The new, modified mesh surgery represents an effective procedure for prolapse and concomitant SUI with a decreased risk of short- and long-term complications.

Microcirculatory effects of sildenafil in experimental testicular torsion in rats.

PURPOSE: Investigate the short-term effect of sildenafil on microcirculation, especially the velocity, the pattern of the flow and the recruitment of the leukocyte in postcapillaries. METHODS: In male Sprague-Dawley rats, the microcirculatory consequences of 60 min experimental testicular torsion, followed by 240 min of reperfusion, were examined. Using fluorescence intravital microscopy, changes in red blood cell velocity in post-capillary venules and rolling as well as adhesion of leukocytes in the postcapillary venules were examined before the torsion and every hour during the reperfusion period. Sildenafil was given 10 min prior to reperfusion (iv 0.7 mg/kg, n = 6), while control animals received saline vehicle (n = 5). RESULTS: The characteristic flow motion disappeared in the affected testicular during the torsion. Red blood cell velocity values were dramatically decreased (by > 50%) and both rolling and adhesion of leukocytes increased during the reperfusion phase. Sildenafil treatment resulted in significantly higher red blood cell velocity values during the entire reperfusion period, but exerted only a temporary positive effect on the plost-ischaemic leukocyte-endothelial interactions. CONCLUSIONS: Intraoperative administration of sildenafil during surgical detorsion may provide marked testicular microperfusion benefits, but failed to influence the overall leukocyte-driven microcirculatory inflammatory reactions.

Effects of intraoperative PEEP optimization on postoperative pulmonary complications and the inflammatory response: study protocol for a randomized controlled trial.

BACKGROUND: Patients undergoing general anesthesia and mechanical ventilation during major abdominal surgery commonly develop pulmonary atelectasis and/or hyperdistention of the lungs. Recent studies show benefits of lung-protective mechanical ventilation with the use of low tidal volumes, a moderate level of positive end-expiratory pressure (PEEP) and regular alveolar recruitment maneuvers during general anesthesia, even in patients with healthy lungs. The purpose of this clinical trial is to evaluate the effects of intraoperative lung-protective mechanical ventilation, using individualized PEEP values, on postoperative pulmonary complications and the inflammatory response. METHODS/DESIGN: A total number of 40 patients with bladder cancer undergoing open radical cystectomy and urinary diversion (ileal conduit or orthotopic bladder substitute) will be enrolled and randomized into a study (SG) and a control group (CG). Standard lung-protective ventilation with a PEEP of 6 cmH2O will be applied in the CG and an optimal PEEP value determined during a static pulmonary compliance (Cstat)-directed PEEP titration procedure will be used in the SG. Low tidal volumes (6 mL/Kg ideal bodyweight) and a fraction of inspired oxygen of 0.5 will be applied in both groups. After surgery both groups will receive standard postoperative management. Primary endpoints are postoperative pulmonary complications and serum procalcitonin kinetics during and after surgery until the third postoperative day. Secondary and tertiary endpoints will be: organ dysfunction as monitored by the Sequential Organ Failure Assessment Score, in-hospital stay, 28-day and in-hospital mortality. DISCUSSION: This trial will assess the possible benefits or disadvantages of an individualized lung-protective mechanical ventilation strategy during open radical cystectomy and urinary diversion regarding postoperative pulmonary complications and the inflammatory response. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02931409 . Registered on 5 October 2016.

Prognostic Factors for Renal Cell Carcinoma Subtypes Diagnosed According to the 2016 WHO Renal Tumor Classification: a Study Involving 928 Patients.

The morphotype and grade of renal cell carcinoma (RCC) in 928 nephrectomies were reclassified according to the 2016 WHO classification in order to analyze the distribution and outcomes of RCC subtypes in Hungary, to assess whether microscopic tumor necrosis is an independent prognostic factor in clear cell RCC, and to study whether a two-tiered grading (low/high) for clear cell and papillary RCC provides similar prognostic information to that of the four-tiered ISUP grading system. 83.4% of the cohort were clear cell, 6.9% papillary, 4.5% chromophobe, 2.3% unclassified, 1.1% Xp11 translocation, 1.1% clear cell papillary, 0.3% collecting duct and 0.1% mucinous tubular and spindle cell RCCs. RCC occurred in 16 patients with end-stage kidney disease and none of them displayed features of acquired cystic kidney disease-associated RCC. The 5-year survival rates were as follows: chromophobe 100%, clear cell papillary 100%, clear cell low-grade 96%, papillary type 1 92%, clear cell high-grade 63%, papillary type 2 65%, unclassified 46%, Xp11 translocation 20%, and collecting duct 0%. The 5-year survival rates in low-grade and high-grade papillary RCC were 95% and 59%, respectively. In clear cell RCC, only the grade, the stage and the positive surgical margin proved to be independent prognostic factors statistically. Overall, papillary RCC occurred relatively infrequently; microscopic tumor necrosis in clear cell RCC did not predict the outcome independently of the tumor grading; and the assignment of clear cell and papillary RCCs into low-grade or high-grade tumors was in terms of survival no worse than the ISUP grading.

[Nocturia]. / Nocturia.

Nocturia is a significantly underestimated disorder, resulting in general worsening of patients' quality of life, while morbidity and mortality are increasing. Several urologic and other pathologic causes can be described in the background including relatively severe conditions. Therefore, accurate evaluation and adequate treatment is recommended. In this review the authors summarize the international literature regarding nocturia. PubMed and ScienceDirect databases were accurately reviewed for the relevant information. Epidemiology, etiology, unfavourable effects, diagnosis and possible treatment options were analysed. They found that symptoms can be releaved by lifestyle changes and traditional therapy in several cases, but clinically significant improvement can be reached using desmopressin in patients suffering from nocturnal polyuria. The authors conclude that nocturia may have negative effects on patients' quality of life and also on the society. Early detection and proper treatment is essential. Orv. Hetil., 2016, 157(36), 1419-1426.

Microcirculatory effects of selective endothelin-A receptor antagonism in testicular torsion.

PURPOSE: Testicular torsion without timely intervention causes incurable damage to the testis. We examined the causative role of microcirculatory injury in torsion induced testicular damage with particular regard to endothelin-A receptor activation. MATERIALS AND METHODS: The microcirculatory consequences of testicular torsion were assessed in the presence or absence of endothelin-A receptor antagonism in rats. Microcirculatory perfusion changes (red blood cell velocity and pulsatile flow pattern alterations) were examined by an orthogonal polarization spectral imaging technique. Microcirculatory inflammatory alterations were assessed by fluorescence intravital video microscopy after 60-minute torsion followed by 240-minute reperfusion. As a specific endothelin-A receptor inhibitor, the antisense homology box derived peptide ETR-p1/fl was applied 10 minutes before reperfusion. Tissue accumulation of leukocytes was estimated by myeloperoxidase activity in tissue biopsies taken at the end of the 4-hour reperfusion period. In further experiments testicular weight as a marker of permanent damage was evaluated 45 days after torsion. RESULTS: The physiological pulsatile flow pattern ceased in the initial phase of reperfusion while leukocyte-endothelial interactions increased throughout the examined reperfusion period. Endothelin-A receptor antagonism caused earlier return of pulsatile flow and recovery of red blood cell velocity, and alleviated microcirculatory inflammatory reactions and atrophy. CONCLUSIONS: Results suggest a pathophysiological role of endothelin-A receptor activation in the pathogenesis of testicular torsion. This effect is related to deterioration in testicular perfusion and activation of microcirculatory inflammatory reactions.

Management of bone metastases in patients with castration-resistant prostate cancer.

Bone metastases are a very common problem in prostate cancer. They are associated with considerable morbidity, adversely affect quality of life and frequently lead to advanced bone events (so-called skeletal-related events, SREs); SREs include fractures, spinal cord compression and the requirement for bone surgery or bone radiation. The aim of this paper was to evaluate currently available treatment options in the prevention and management of SREs and bone metastases in men with castration-resistant prostate cancer and to outline the importance of interdisciplinary management strategies. It also discusses the diagnostic workup of osseous metastases and practical considerations for the utilization of bone-targeted therapies in accordance with current guidelines to provide a consensus for special and/or difficult clinical situations.

Involvement of large-conductance Ca(2+) -activated K(+) channels in both nitric oxide and endothelium-derived hyperpolarization-type relaxation in human penile small arteries.

Large-conductance Ca(2+) -activated K(+) channels (BKC a ), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, opening of BKC a channels leads to relaxation of corporal smooth muscle, which is essential during erection; however, there is little information on the role of BKC a channels located in penile vascular smooth muscle. This study was designed to investigate the involvement of BKC a channels in endothelium-dependent and endothelium-independent relaxation of human intracavernous penile arteries. In human intracavernous arteries obtained in connection with transsexual operations, change in isometric force was recorded in microvascular myographs, and endothelium-dependent [nitric oxide (NO) and endothelium-derived hyperpolarization (EDH)-type] and endothelium-independent (NO-donor) relaxations were measured in contracted arteries. In penile small arteries contracted with phenylephrine, acetylcholine evoked NO- and EDH-type relaxations, which were sensitive to iberiotoxin (IbTX), a selective blocker of BKC a channels. Iberiotoxin also inhibited relaxations induced by a NO-donor, sodium nitroprusside. NS11021, a selective opener of BKC a channels, evoked pronounced relaxations that were inhibited in the presence of IbTX. NS13558, a BKC a -inactive analogue of NS11021, failed to relax human penile small arteries. Our results show that BKC a channels are involved in both NO- and EDH-type relaxation of intracavernous penile arteries obtained from healthy men. The effect of a selective opener of BKC a channels also suggests that direct activation of the channel may be an advantageous approach for treatment of impaired endothelium-dependent relaxation often associated with erectile dysfunction.

Surgical solutions for the complications of the Vaseline self-injection of the penis.

INTRODUCTION: Penile girth enhancement by the injection of Vaseline is an existing practice. Many cases develop severe complications that need surgery. AIM: To report on the reconstructive surgical solutions of the complications of Vaseline self-injection and the outcomes. To develop a modification of a one-step reconstruction method involving the use of pedicled scrotal flaps. MAIN OUTCOME MEASURES: The complications and their surgical solutions were classified as regards severity and difficulty. The outcomes were observed and a newly introduced one-step surgical method was investigated. METHODS: Seventy-eight consecutive patients (87.2% of them with a history of imprisonment) were divided into three groups. In group A, aesthetic penile defects or phimosis caused by the Vaseline necessitated circumcision or local excision. In group B, the whole penile skin was involved, and total skin removal and two- or (a newly modified) one-step reconstructive surgery were performed. In group C, both the whole penile skin and the scrotum were involved: complete skin removal and skin grafting or skin pedicled flap transplantation were carried out. RESULTS: In five cases in group B, postoperative skin necrosis made a second operation necessary. There was one intraoperative urethral injury, where a urethral fistula developed and a second urethral reconstruction was performed. There was no major complication with the newly developed one-stage pedicled flap procedure. At the end of the therapy, all the cases were healed. All of the patients reported successful sexual intercourse after the operations and 91% were satisfied with the result. CONCLUSIONS: The complications depend mainly on the amount of Vaseline injected, the hygienic circumstances, and the personal tolerability. In the worst cases, only radical skin removal and skin transplantation can solve the problem. The newly developed one-step arterial branch-preserving scrotal skin flap reconstruction appears to be a suitable and cost-effective solution for these patients.

Hungarian "jailhouse rock": incidence and morbidity of Vaseline self-injection of the penis.

INTRODUCTION: Vaseline self-injection into the penis is currently a popular procedure in prisons. Since such injections are illegal, severe complications of the procedure can often remain hidden. AIM: To identify the incidence, motivation, and morbidity of Vaseline self-injection into the penis among inmates. METHODS: A total of 4,735 inmates at the largest Hungarian prisons were asked to complete a questionnaire relating to their sexual life, whether they had self-injected Vaseline into their penis, the motivation leading them to resort to Vaseline self-injection, any complications observed and the level of satisfaction attained. MAIN OUTCOME MEASURES: A 17-point questionnaire on the circumstances, motivations, and complications of Vaseline self-injection among prisoners. RESULTS: Of the 1,905 responders, 15.7% admitted Vaseline self-injection. Only around one-fifth of the Vaseline injected subjects had not been satisfied with the original size of their penis and their sexual life up to the time of the injection, a proportion similar to that among Vaseline nonusers. While the satisfaction with the sexual life became significantly worse after the Vaseline injection, the satisfaction with the penis size did not change and an erectile dysfunction developed de novo in 21.4% of cases. The most common motivation for self-injection was a recommendation by another inmate; it was rarely recommended by a sexual partner. Complications had developed among 25.4% of the Vaseline users and 50.3% of them were not satisfied with the result of the Vaseline injection. Of the Vaseline users, 22.4% regretted the self-injection, while the rate among those who had developed complications was 53%. CONCLUSIONS: The self-injection of Vaseline into the penile skin proved to be somewhat of a trend among these inmates. The complications depended mainly on the amount of Vaseline injected, the poor hygienic circumstances, and the personal tolerability. Increased awareness is needed for the prevention of this social, psychological, and physical problem.