Novel thiazolopyridine derivatives of diflapolin as dual sEH/FLAP inhibitors with improved solubility.

Inflammatory responses are orchestrated by a plethora of lipid mediators, and perturbations of their biosynthesis or degradation hinder resolution and lead to uncontrolled inflammation, which contributes to diverse pathologies. Small molecules that induce a switch from pro-inflammatory to anti-inflammatory lipid mediators are considered valuable for the treatment of chronic inflammatory diseases. Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) are afflicted with side effects caused by the inhibition of beneficial prostanoid formation and redirection of arachidonic acid (AA) into alternative pathways. Multi-target inhibitors like diflapolin, the first dual inhibitor of soluble epoxide hydrolase (sEH) and 5-lipoxygenase-activating protein (FLAP), promise improved efficacy and safety but are confronted by poor solubility and bioavailability. Four series of derivatives bearing isomeric thiazolopyridines as bioisosteric replacement of the benzothiazole core and two series additionally containing mono- or diaza-isosteres of the phenylene spacer were designed and synthesized to improve solubility. The combination of thiazolo[5,4-b]pyridine, a pyridinylen spacer and a 3,5-Cl2-substituted terminal phenyl ring (46a) enhances solubility and FLAP antagonism, while preserving sEH inhibition. Moreover, the thiazolo[4,5-c]pyridine derivative 41b, although being a less potent sEH/FLAP inhibitor, additionally decreases thromboxane production in activated human peripheral blood mononuclear cells. We conclude that the introduction of nitrogen, depending on the position, not only enhances solubility and FLAP antagonism (46a), but also represents a valid strategy to expand the scope of application towards inhibition of thromboxane biosynthesis.

Totally tubeless, tubeless, and tubed percutaneous nephrolithotomy for treating kidney stones.

BACKGROUND: Percutaneous nephrolithotomy (PNL) is the standard of care for removing large kidney stones (> 2 cm). Once the procedure is complete, different exiting strategies exist to manage the percutaneous tract opening, including placement of an external nephrostomy tube, placement of an internal ureteral stent, or no external or internal tube. The decision to place or not place a tube is handled differently among clinicians and may affect patient outcomes. OBJECTIVES: To assess the effects of tubeless PNL (with ureteral stenting), totally tubeless PNL (without ureteral stenting or nephrostomy), and standard PNL (nephrostomy only) for the treatment of kidney stones in adults. SEARCH METHODS: We performed a systematic literature search in multiple biomedical databases (CENTRAL, MEDLINE, Embase, Web of Science), as well as in two clinical trial registries. We also handsearched reference lists of relevant publications and conference proceedings. We applied no language restrictions. The latest search update was conducted in September 2022. SELECTION CRITERIA: We included randomized controlled and quasi-randomized controlled trials of adult patients who received tubeless, totally tubeless, or standard PNL for treating kidney stones. We defined tubeless PNL as no nephrostomy tube, but ureteral stenting, while totally tubeless PNL meant no nephrostomy tube or ureteral stenting. Both interventions were compared to standard PNL with placement of a nephrostomy tube (only). We considered access tubes of any sizes. We only considered unilateral PNL with single-tract access. There were no exclusions on stone composition, size, or location. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, assessed risk of bias, and rated the certainty of evidence using GRADE. Primary outcomes were severe adverse events and postoperative pain, and secondary outcomes were operating time, length of hospital stay, and stone-free rate. We used the random-effects model for meta-analysis. MAIN RESULTS: We included 10 studies in the review. Participant age varied among studies, ranging from 20 to 60 years. Detailed information on stone characteristics was rarely presented. Tubeless PNL versus standard PNL We are very uncertain whether there is a difference in severe adverse events (SAEs) between tubeless PNL and standard PNL (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.14 to 16.46; I2 = 42%; 2 studies, 46 participants; very low-certainty evidence). Tubeless PNL may have little to no effect on pain on postoperative day one (mean difference (MD) 0.56 lower, 95% CI 1.34 lower to 0.21 higher; I2 = 84%; 4 studies, 186 participants; low-certainty evidence), and probably results in little to no difference in operating room time (MD 0.40 longer (in minutes), 95% CI 4.82 shorter to 5.62 longer; I2 = 0%; 3 studies, 81 participants; moderate-certainty evidence). Tubeless PNL may reduce length of hospital stay (MD 0.90 shorter, 95% CI 1.45 shorter to 0.35 shorter; I2 = 84%; 6 studies, 238 participants; low-certainty evidence). We are very uncertain of the effect of tubeless PNL on blood transfusions (RR 0.64, 95% CI 0.16 to 2.52; I2 = 0%; 4 studies, 161 participants; very low-certainty evidence), sepsis or fever (RR 0.50, 95% CI 0.05 to 4.75; I2 = not applicable; 2 studies, 82 participants; very low-certainty evidence), or readmissions (RR 1.00, 95% CI 0.07 to 14.21; I2 = not applicable, 1 study, 24 participants; very low-certainty evidence). Totally tubeless versus standard PNL Totally tubeless PNL may result in lower SAE rates (RR 0.49, 95% CI 0.19 to 1.25; I2 = 0%; 2 studies, 174 participants; low-certainty evidence) and pain on postoperative day one (MD 3.60 lower, 95% CI 4.24 lower to 2.96 lower; I2 = Not applicable; 1 study, 50 participants; low-certainty evidence). Totally tubeless PNL may result in little to no difference in operating room time (MD 6.23 shorter (in minutes), 95% CI 14.29 shorter to 1.84 longer; I2 = 72%; 2 studies, 174 participants; moderate-certainty evidence) and sepsis or fever (RR 0.33, 95% CI 0.01 to 7.97; I2 = not applicable; 1 study, 90 participants; low-certainty evidence). Totally tubeless PNL likely shortens the length of hospital stay (MD 1.55 shorter, 95% CI 1.82 shorter to 1.29 shorter; I2 = 0%; 4 studies, 274 participants; moderate-certainty evidence). We are very uncertain of the effect of totally tubeless PNL on blood transfusions (RR 0.62, 95% CI 0.26 to 1.48; I2 = 0%; 4 studies, 274 participants; very low-certainty evidence) or readmissions (RR not estimable, 95% CI not estimable; I2 = not applicable; 1 study, 50 participants; very low-certainty evidence). We found no studies comparing tubeless mini versus standard mini-PNL or totally tubeless mini versus standard mini-PNL. AUTHORS' CONCLUSIONS: When comparing tubeless to standard PNL with regard to the predefined primary outcomes of this review, there may be little difference in early postoperative pain, while we are very uncertain of the effect on SAEs. People treated with tubeless PNL may benefit from a reduced length of stay compared to standard PNL. When comparing totally tubeless to standard PNL, early postoperative pain and severe adverse events may be reduced with totally tubeless PNL. The certainty of evidence by outcome was mostly very low (range: moderate to very low) for the comparison of tubeless to standard PNL and low (range: moderate to very low) for the comparison of totally tubeless to standard PNL. The most common reasons for downgrading the certainty of the evidence were study limitations, inconsistency, and imprecision. We did not find randomized trial evidence for other comparisons. Overall, further and higher-quality studies are needed to inform clinical practice.

Thermal effects of thulium: YAG laser treatment of the prostate-an in vitro study.

PURPOSE: To objectively determine whether there is potential thermal tissue damage during Tm:YAG laser-based LUTS treatment. METHODS: Our experimental model was comprised of a prostatic resection trainer placed in a 37 °C water bath. In a hollowed-out central area simulating the urethral lumen, we placed a RigiFib 800 fibre, irrigation inflow regulated with a digital pump, and a type K thermocouple. A second thermocouple was inserted 0.5/1 cm adjacently and protected with an aluminum barrier to prevent it from urethral fluid. We investigated continuous and intermittent 120 W and 80 W laser application with various irrigation rates in eight measurement sessions lasting up to 14 min. Thermal measurements were recorded continuously and in real-time using MatLab. All experiments were repeated five times to balance out variations. RESULTS: Continuous laser application at 120 W and 125 ml/min caused a urethral ∆T of ~ 15 K and a parenchymal temperature increase of up to 7 K. With 50 ml/min irrigation, a urethral and parenchymal ∆T of 30 K and 15 K were reached, respectively. Subsequently and in absence of laser application, prostatic parenchyma needed over 16 min to reach baseline body temperature. At 80 W lower temperature increases were reached compared to similar irrigation but higher power. CONCLUSIONS: We showed that potentially harming temperatures can be reached, especially during high laser power and low irrigation. The heat generation can also be conveyed to the prostate parenchyma and deeper structures, potentially affecting the neurovascular bundles. Further clinical studies with intracorporal temperature measurement are necessary to further investigate this potentially harming surgical adverse effect.

Synthesis and structure-activity relationships for some novel diflapolin derivatives with benzimidazole subunit.

A series of derivatives of the potent dual soluble epoxide hydrolase (sEH)/5-lipoxygenase-activating protein (FLAP) inhibitor diflapolin was designed, synthesised, and characterised. These novel compounds, which contain a benzimidazole subunit were evaluated for their inhibitory activity against sEH and FLAP. Molecular modelling tools were applied to analyse structure-activity relationships (SAR) on both targets and to predict solubility and gastrointestinal (GI) absorption. The most promising dual inhibitors of these series are 5a, 6b, and 6c.

A nationwide registry for recurrent urolithiasis in the upper urinary tract - The RECUR study protocol.

BACKGROUND: Urinary stone disease is a widespread disease with tremendous impact on those affected and on societies around the globe. Nevertheless, clinical and health care research in this area seem to lag far behind cardiovascular diseases or cancer. This may be due to the lack of an immediate deadly threat from the disease and therefore less public and professional interest. However, the patients suffer from recurring, sometimes intense pain and often must be treated in hospital. Long-term morbidity includes doubled rates of chronic kidney disease and arterial hypertension after at least one stone-related event. Observational studies, more specifically, registries and other electronic data sets have been proposed as a means of filling critical gaps in evidence. We propose a nationwide digital and fully automated registry as part of the German Ministry for Education and Research (BMBF) call for the "establishment of model registries". METHODS: RECUR builds on the technical infrastructure of Germany's Medical Informatics Initiative. Local data integration centres (DIC) of participating medical universities will collect pseudonymized and harmonized data from respective hospital information systems. In addition to their clinical data, participants will provide patient reported outcomes using a mobile patient app. Scientific data exploration includes queries and analysis of federated data from DICs of eleven participating sites. All primary patient data will remain at the participating sites at all times. With comprehensive data from this longitudinal registry, we will be able to describe the disease burden, to determine and validate risk factors, and to evaluate treatments. Implementation and operation of the RECUR registry will be funded by the BMBF for five years. Subsequently, the registry is to be continued by the German Society of Urology without significant costs for study personnel. DISCUSSION: The proposed registry will substantially improve the structural and procedural framework for patients with recurrent urolithiasis. This includes advanced diagnostic algorithms and treatment pathways. The registry will help us identify those patients who will most benefit from specific interventions to prevent recurrences. The RECUR study protocol and the registry's technical architecture including full digitalization and automation of almost all registry-associated proceedings can be transferred to future registries. TRIAL REGISTRATION: This study is registered at the German Clinical Trial Register (Deutsches Register Klinischer Studien), DRKS-ID DRKS00026923 , date of registration January, 11th 2022.

Radiation exposure during retrograde intrarenal surgery (RIRS): a prospective multicenter evaluation.

PURPOSE: Retrograde intrarenal surgery (RIRS) may require extensive X-ray usage. We evaluated the impact of preoperative surgeon briefing regarding the inclusion and evaluation of fluoroscopy time (FT) and dose area product (DAP) in a multicenter study on the applied X-ray usage. METHODS: A prospective multicenter study of 6 tertiary centers was performed. Each center recruited up to 25 prospective patients with renal stones of any size for RIRS. Prior to study´s onset, all surgeons were briefed about hazards of radiation and on strategies to avoid high doses in RIRS. Prospective procedures were compared to past procedures, as baseline data. FT was defined as the primary outcome. Secondary parameters were stone-free rate (SFR), complications according to the Clavien, SATAVA and postureteroscopic lesion scale. Results were analyzed using T test, chi-squared test, univariate analysis and confirmed in a multivariate regression model. RESULTS: 303 patients were included (145 retro- and 158 prospective). Mean FT and DAP were reduced from 130.8 s/565.8 to 77.4 s/357.8 (p < 0.05). SFR was improved from 85.5% to 93% (p < 0.05). Complications did not vary significantly. Neither stone position (p = 0.569), prestenting (p = 0.419), nor surgeons' experience (> 100 RIRS) had a significant impact on FT. Significant univariate parameters were confirmed in a multivariate model, revealing X-ray training to be radiation protective (OR - 44, p = 0.001). CONCLUSIONS: Increased surgeon awareness of X-ray exposure risks has a significant impact on FT and DAP. This "awareness effect" is a simple method to reduce radiation exposure for the patient and OR staff without the procedures´ outcome and safety being affected.

[RECUR - Establishment of An Automated Digital Registry for Patients with Recurrent Stones in the Upper Urinary Tract]. / RECUR ­ Aufbau eines automatisierten digitalen Registers für Patient*innen mit rezidivierenden Steinen des oberen Harntraktes.

Kidney stones, like cardiovascular diseases and diabetes mellitus, affect a large number of people. Patients suffer from acute pain, repeated hospitalizations and associated secondary diseases, such as arterial hypertension and renal insufficiency. This results in considerable costs for the society and its health care system. The recurrence rate is as high as 50%. The registry for RECurrent URolithiasis (RECUR) aims to fill existing evidence gaps. The prospective and longitudinal RECUR registry is funded by the German Ministry of Education and Science (BMBF). It is based on the digital infrastructure of the German Medical Informatics Initiative (MII). RECUR aims to include patients that have suffered from more than one stone occurrence and treated at any one of the ten participating university hospitals of the MIRACUM consortium. The intention is to obtain new information on risk factors and to evaluate different diagnosis and treatment algorithms. Along with the data form the patient's Electronic Health Records (EHR), the RECUR project will also collect Patient Reported Outcomes data from patients with recurrent kidney stones. These data will be collected at participating sites using digital questionnaires via a smartphone app. These data will be merged with medical data from the hospital information systems and saved in the MII research data repositories. The RECUR registry has a model character due to its fully federated, digital approach. This allows the recruitment of many patients, the collection of a wide range of data and their processing with low administrative and personnel costs.

Thermal effects of Ho:YAG laser lithotripsy during retrograde intrarenal surgery and percutaneous nephrolithotomy in an ex vivo porcine kidney model.

PURPOSE: To evaluate the thermal effect of high-power holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy in flexible/semirigid ureteroscopy (fURS/sURS) and percutaneous nephrolithotomy (PNL) in a standardized ex vivo porcine kidney model with real-time temperature assessment. METHODS: The experimental setup consisted of three models designed to evaluate the thermal effects of Ho:YAG laser lithotripsy in fURS, sURS and PNL, respectively. In all setups, a postmortem porcine kidney was placed in a 37 °C water bath. Three thermocouples were inserted into the renal parenchyma while a flexible thermocouple was placed 3-4 mm proximal to the laser fiber to measure temperature variations in the collecting system. The thermal impact was evaluated in relation to laser power between 5 and 100 W and various irrigation rates (37 °C, 0-100 ml/min). RESULTS: In all three experimental setups, sufficient irrigation was required to prevent potentially damaging temperatures into the renal pelvis and parenchyma. Even 5 W in fURS can lead to a potentially harming temperature rise if insufficient irrigation is applied. Particularly, high-power settings ≥ 30 W carry an elevated risk for critical temperature rises. The results allow the definition of a specific irrigation threshold for any power setting to prevent critical temperatures in the present study design. CONCLUSIONS: Ho:YAG laser lithotripsy bears the risk of thermal damages to the urinary tract even at low-power settings if inadequate irrigation is applied. Sufficient irrigation is mandatory to perform safe Ho:YAG laser lithotripsy. Based on the results, we developed a formula calculating the approximate ΔT for irrigation rates ≥ 30 ml/min: ΔT = 15 K × (power [W]/irrigation [ml/min]).

How to compete with Google and Co.: big data and artificial intelligence in stones.

PURPOSE OF REVIEW: To elucidate the keywords big data and artificial intelligence and corresponding literature in the field of urolithiasis. RECENT FINDINGS: Numbers of publications on big data and artificial intelligence in the field of urolithiasis are rising, but still low. Most publications describe the development, testing, and validation of automated computational analyses of clinical data sets and/or images in a preclinical setting. SUMMARY: In the field of digital health services, there is a discrepancy between the enormous commitment of large private companies and investments of public funds. This situation means a still small number of medical publications on this topic in the urolithiasis field. Nevertheless, as doctors and scientists, we should try to provide our patients with secure and worthwhile digital services.

Concept to gain trust for a German personal health record system using public cloud and FHIR.

OBJECTIVE: Although a national Personal Health Record (PHR) infrastructure was supposed to have been introduced in Germany by law in 2006 and different providers are entering the market, no system has yet been widely adopted in Germany. There is also little information available on how current technical advancements affect German patients' and physicians' trust in PHR systems. METHODS: Supporting scenarios obtained from clinicians, this study proposes a concept for a German PHR system using a public cloud infrastructure, smartphone access and focusing on trust, privacy, and interoperability. In advance to an eventual implementation, a multi-center questionnaire study has been conducted to predict patients' and physicians' intention to use that system and evaluate their trust in different providers of such a system. RESULTS: Our results show that both patients and physicians are highly likely to use the PHR based on the present concept. Trust in healthcare providers exceeds trust in other institutions like private companies, health insurance companies, or even governmental institutions when offering such a PHR system. CONCLUSIONS: We recommend the implementation of this PHR system. To maximize patients' and physicians' trust in the system, it should be offered to patients by their healthcare provider. Further evaluation regarding its actual adoption and expected improvement in patient outcome based on the scenarios is advisable.

Stone-Free Rate after Treating Kidney Stones Exceeding 10 mm via Flexible Ureteroscopy: Can Endoscopic Assessment Replace Low-Dose Computed Tomography Control?

INTRODUCTION: It is unclear whether endoscopic assessment of the stone-free rate after flexible ureteroscopy (fURS) is as effective as assessment with low-dose computed tomography (CT) scan. METHODS: Prospective documentation of patients with kidney stones > 10 mm diameter from 2 different centers (Freiburg, Regensburg), who underwent fURS and were declared to be endoscopically completely stone-free. Low-dose CT control performed 4-8 weeks postoperatively. RESULTS/CONCLUSION: Thirty-eight patients were treated between October 2015 and August 2016 (12 F, 26 M). Average age was 55.9 years (range 19-82, SD 17.24), and body mass index was 29.7 kg/m2 (range 23.5-42.5, SD 4.37). There were 2.0 (range 1-7, SD 1.55) stones with a mean diameter of 15 mm (range 10-40, SD 6.78) per kidney. Mean surgery time was 74 min (range 38-124, SD 24.28), and lithotripsy was necessary in 33 cases. CT was performed 5.4 weeks afterwards (range 4-8, SD 1.43). One patient had a 2 mm residual which was extracted by URS. Strictly speaking, endoluminal stone removal control failed in only that patient, yielding a negative predictive value of 97%. A routine postoperative CT scan would thus appear unnecessary in the case of negative endoscopic control for residual fragments and should be avoided to reduce radiation exposure. Further investigations with larger patient populations are necessary.

Thermal effects of Ho: YAG laser lithotripsy: real-time evaluation in an in vitro model.

PURPOSE: To evaluate the thermal effect of Ho:YAG laser lithotripsy in a standardized in vitro model via real-time temperature measurement. METHODS: Our model comprised a 20 ml test tube simulating the renal pelvis that was immersed in a 37 °C water bath. Two different laser fibers [FlexiFib (15-45 W), RigiFib 1000 (45-100 W), LISA laser products OHG, Katlenburg-Lindau, Germany] were placed in the test tube. An Ho:YAG 100 W laser was used in all experiments (LISA). Each experiment involved 120 s of continuous laser application, and was repeated five times. Different laser settings (high vs. low frequency, high vs. low energy, and long vs. short pulse duration), irrigation rates (0 up to 100 ml/min, realized by several pumps), and human calcium oxalate stone samples were analyzed. Temperature data were acquired by a real-time data logger with thermocouples (PICO Technology, Cambridgeshire, UK). Real-time measurements were assessed using MatLab®. RESULTS: Laser application with no irrigation results in a rapid increase in temperature up to ∆28 K, rising to 68 °C at 100 W. Low irrigation rates yield significantly higher temperature outcomes. Higher irrigation rates result immediately in a lower temperature rise. High irrigation rates of 100 ml/min result in a temperature rise of 5 K at the highest laser power setting (100 W). CONCLUSIONS: Ho:YAG laser lithotripsy might be safe provided that there is sufficient irrigation. However, high power and low irrigation resulted in potentially tissue-damaging temperatures. Laser devices should, therefore, always be applied in conjunction with continuous, closely monitored irrigation whenever performing Ho:YAG laser lithotripsy.

Low-pressure monopolar electroresection of the prostate for glands sized > 70 vs. < 70 cc performed with continuous irrigation and suprapubic suction: perioperative and long-term outcome.

PURPOSE: To evaluate long-term efficacy and safety of low-pressure transurethral resection of the prostate for prostates < 70 cc (group 1) vs. > 70 cc (group 2). PATIENTS AND METHODS: In this study patients operated with monopolar TURP between 2009 and 2012 were evaluated retrospectively. During surgery a specially designed trocar (18 Fr) was placed suprapubically and connected to a suction pump to maintain stable low-pressure conditions. After sample size calculations, long-term follow-up was completed for 70 invited patients in each group up to 9/2015. RESULTS: Follow-up period was 57 vs. 56 months for group 1 and 2, respectively (p = 0.56). At baseline there was no significant difference in age, IPSS, peak flow, and post void residual (PVR). Mean prostate volume was 47 cc (15-65) vs. 100 cc (70-163). Mean operating time was 55.4 vs. 82.6 min (p = 0.00). Blood transfusion was necessary in 0.0 vs. 2.9% (p = 0.16), and 0.0 vs. 1.4% developed TUR syndrome (p = 0.32). At follow-up mean relative improvement in IPSS was 63 vs. 57% (p = 0.29), QoL 64 vs. 64% (p = 0.93), peak flow 139 vs. 130% (p = 0.85), and PVR 58 vs. 63% (p = 0.80). Long-term complications included recurring adenoma in 1.4 vs. 4.3% (p = 0.31), and stricture in 7.2 vs. 5.8% (p = 0.73). 1 patient in each group reported worsening incontinence symptoms. CONCLUSIONS: In terms of safety and efficacy, the aforementioned modality of standardized monopolar TURP using suprapubic suction was non-inferior for prostates > 70 cc compared to the same procedure for prostates < 70 cc. This technique is a potential low-cost alternative for clinics that cannot afford modern laser approaches. STUDY REGISTER NUMBER: DRKS00006527.

The stone surgeon in the mirror: how are German-speaking urologists treating large renal stones today?

OBJECTIVE: To elucidate the current treatment strategies of LRS in German-speaking Europe. Little is known about the treatment of large renal stones (LRS > 3 cm) in daily urological practice. LRS therapy can be, however, challenging and hazardous. MATERIALS AND METHODS: A 39 item web-based survey was performed among urologists listed by the German, Austrian and Swiss Associations of Urology, addressing professionals treating LRS "on their own" and working in a German-speaking country. Uniparametric descriptions indicated as absolute numbers and percentages without p values, simple linear associations and bubble plots without arithmetic means or bar charts with standard deviation between targeted parameters and percentages were used. RESULTS: 266 of the 6586 responding urologists claimed to treat urinary stones on a regular basis. The majority of them were male (90.2%) and over 50 years old (42.9%). Most stones are treated in non-university hospitals (69.5%). 81.9% of all the institutions treat more than 150 cases/y. Open surgery is still performed in 45.5% of the centres, laparoscopy in 32%. Percutaneous nephrolithotomy (PNL) is the primary treatment option. Antimicrobial strategies vary considerably. Serious complications seem to be rare. However, quite a few responders reported treatment-related deaths. The main limitation is the absolute number of urologists performing LRS treatment, which is unknown. CONCLUSIONS: The German-speaking urologist treating LRS is a male and over 50. Although he performs PNL primarily, he is not averse to open surgery and SWL. He applies guidelines and employs modern equipment. Only antimicrobial strategies are out of line with the international standards.

Combined prostatic urethral lift and remodeling of the prostate and bladder neck: a modified transurethral approach in the treatment of symptomatic lower urinary tract obstruction.

PURPOSE: The aim of the study was to evaluate the feasibility and safety of combining prostatic urethral lift (PUL) and a limited resection of the prostatic middle lobe or bladder neck incision in the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: Twenty-eight patients were treated at two tertiary centers and followed prospectively. Patient evaluations included patient characteristics, relief of LUTS symptoms, erectile and ejaculatory function, continence, operative time and adverse events. Patients were followed for a mean of 10.9 months. RESULTS: Patient characteristics were as follows: age 66 years (46-85), prostate volume 39.6 cc (22-66), preoperative IPSS/AUASI 20 (6-35)/QoL 3.9 (1-6)/peak flow 10.5 mL/s (4.0-19)/post-void residual volume (PVR) 123 mL (0-500). Mean operating time was 31 min (9-55). Postoperative complications were minor except for the surgical retreatment of one patient for blood clot retention (Clavien 3b). One patient required catheterization due to urinary retention. Reduction of symptoms (IPSS - 59.6%), increase in QoL (+ 49.0%), increase in flow (+ 111.5%), and reduction of PVR (- 66.8%) were significant. Antegrade ejaculation was always maintained. CONCLUSION: Our data suggest that a combination of PUL and transurethral surgical techniques is feasible, safe, and effective. This approach may be offered to patients with moderate size prostates including those with unfavorable anatomic conditions for PUL. This procedure is still 'minimally invasive' and preserves sexual function. In addition, it may add to a higher functional efficacy compared to PUL alone. STUDY REGISTER NUMBER: DRKS00008970.

Viability and biocompatibility of an adhesive system for intrarenal embedding and endoscopic removal of small residual fragments in minimally-invasive stone treatment in an in vivo pig model.

PURPOSE: To evaluate the viability and biocompatibility of a novel, patented bioadhesive system for intrarenal embedding and retrieval of residual fragments after endoscopic lithotripsy. Complete stone clearance via active removal of residual fragments (RF) after intracorporeal laser lithotripsy may be time-consuming and fail in many cases. Therefore, the novel adhesive has been developed and evaluated for the first time in an in vivo pig model in the present work. METHODS: Four female domestic pigs underwent flexible ureteroscopy (RIRS) or percutaneous nephrolithotomy (PNL) under general anesthesia (8 kidneys, 4 × RIRS, 4 × PNL) evaluating the bioadhesive system. INTERVENTIONS: RIRS without adhesive system (sham procedure, kidney I); 3 × RIRS using the bioadhesive system (kidneys II-IV); and 4 × PNL using the bioadhesive system (V-VIII). We endoscopically inserted standardized human stone probes followed by comminution using Ho:YAG lithotripsy. The bioadhesive (kidney II-VIII) was then applied and the adhesive-stone fragment complex extracted. After nephrectomy, all kidneys were evaluated by two independent, blinded pathologists. Endpoints were the procedure's safety and adhesive system's biocompatibility. RESULTS: We observed no substantial toxic effects. We were able to embed and remove 80-90% of fragments. However, because of the pig's hampering pyelocaliceal anatomy, a quantified, proportional assessment of the embedded fragments was compromised. CONCLUSIONS: For the first time, we demonstrated the proven feasibility and safety of this novel bioadhesive system for embedding and endoscopically removing small RF in conjunction with a lack of organ toxicity in vivo.

Prostatic urethral lift vs transurethral resection of the prostate: 2-year results of the BPH6 prospective, multicentre, randomized study.

OBJECTIVES: To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception. PATIENTS AND METHODS: A total of 80 patients with lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) were enrolled in a prospective, randomized, controlled, non-blinded study conducted at 10 European centres. The BPH6 responder endpoint assessed symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation and safety. Additional evaluations of patient perspective, quality of life and sleep were prospectively collected, analysed and presented for the first time. RESULTS: Significant improvements in International Prostate Symptom Score (IPSS), IPSS quality of life (QoL), BPH Impact Index (BPHII), and maximum urinary flow rate (Qmax ) were observed in both arms throughout the 2-year follow up. Change in IPSS and Qmax in the TURP arm were superior to the PUL arm. Improvements in IPSS QoL and BPHII score were not statistically different between the study arms. PUL resulted in superior quality of recovery, ejaculatory function preservation and performance on the composite BPH6 index. Ejaculatory function bother scores did not change significantly in either treatment arm. TURP significantly compromised continence function at 2 weeks and 3 months. Only PUL resulted in statistically significant improvement in sleep. CONCLUSION: PUL was compared to TURP in a randomised, controlled study which further characterized both modalities so that care providers and patients can better understand the net benefit when selecting a treatment option.

Surgical therapy of prostatitis: a systematic review.

PURPOSE: The clinical term "prostatitis" refers to a clinical syndrome defined by the following 4 distinct entities: acute bacterial prostatitis (category 1), chronic bacterial prostatitis (category 2), chronic prostatitis/chronic pelvic pain syndrome (category 3), and asymptomatic prostatitis (category 4) The etiology of the chronic forms is still not fully understood and choice of therapy is often debated. The objective of this systematic review is to collect evidence on the surgical treatment of the chronic form of prostatitis and to evaluate its clinical implication. METHODS: We performed a systematic literature search and identified 6683 relevant publications, of which 16 were included in the review. RESULTS: Transurethral prostate resection was performed in 110 patients; 78 patients (70%) were reported as "cured", 16 patients (15%) as improved, and 16 patients (15%) as unchanged. Radical prostatectomy was performed in 21 patients; a full resolution of prostatitis related symptoms was reported for 20 patients (95%). No increased rates of complications or unusual complications were noted. CONCLUSIONS: Surgical therapy of chronic bacterial prostatitis or chronic pelvic pain syndrome might be a viable option; however, since little evidence is currently available and no randomized controlled trials have been conducted, the presently available data does not provide a base for clinical decisions.

Is Endoscopic Vasectomy Just a Dream: An ex vivo Study on Feasibility and Reliability of Endoluminal Occlusion of Porcine Vas Deferens.

INTRODUCTION AND AIM: Surgical vasectomy remains the gold standard for fertility control in men. Endoluminal occlusion of the seminal ducts, thus avoiding an external incision, may become an appealing alternative to this approach. As our group has shown, nontraumatic endoscopic inspection of the seminal ducts is feasible in the human cadaver. We investigated the feasibility and reliability of occlusion using several commercially available medical sealing agents in the porcine vas deferens (VD). METHODS AND MAIN OUTCOME MEASURES: Tests were conducted using 25 porcine spermatic ducts (10 cm length) ex vivo. The explanted specimens were fixed and cannulated using the Seldinger technique. We administered 5 different agents (n-butyle-2-cyanoacrylate, n-butyle-2-cyanoacrylate in combination with a platinum vascular coil, Tissucol Duo S®, Gelita Spon® and AFP Plug®) endoluminally. Tightness was evaluated after 5, 15, 60, 360, 720, and 1,440 min for each of the five grades, respectively, using a solution of methylene blue and saline injected under controlled pressure of 300 mm Hg followed by histological examination. RESULTS: All agents were administered into the porcine seminal ducts (4 out of 5 via a ureteric catheter). Gelita Spon® and Tissucol Duo S® did not occlude the lumen sufficiently, whereas n-butyle-2-cyanoacrylate, n-butyle-2-cyanoacrylate in combination with coil, Tissucol Duo and AFP Plug® performed satisfactorily. In particular, cyanoacrylate combined with a coil was able to close the seminal duct tightly and for a long time. Histological findings confirmed this sealant's gapless adhesion. AFP Plug® application revealed similarly good results. However, its form needs to be optimized to ensure its suitability for endoscopic use. CONCLUSION: Various developments regarding minimally invasive fertility control methods have been underway for decades. Further miniaturization of endoscopy and novel materials may pave the way for endoscopic fertility control in males in the future. We demonstrated the potential of commercially available medical sealing agents to reliably occlude the porcine VD.

Novel Biocompatible Adhesive for Intrarenal Embedding and Endoscopic Removal of Small Residual Fragments after Minimally Invasive Stone Treatment in an Ex Vivo Porcine Kidney Model: Initial Evaluation of a Prototype.

PURPOSE: Residual fragments related to endoscopic intracorporeal lithotripsy are a challenging problem. The impact of residual fragments remains a subject of discussion and growing evidence highlights that they have a central role in recurrent stone formation. Therefore, we developed a novel bioadhesive system for intrarenal embedding and retrieval of residual fragments after endoscopic lithotripsy in an ex vivo porcine kidney model. MATERIALS AND METHODS: In a standardized setting 30 human stone fragments 1 mm or less were inserted in the lower pole of an ex vivo porcine kidney model. We assessed the extraction efficacy of flexible ureteroscopy using the bioadhesive system in 15 preparations and a conventional retrieval basket in 15. Outcomes were compared regarding the endoscopic and macroscopic stone-free rate, and overall time of retrieval. RESULTS: Embedding and retrieving the residual fragment-bioadhesive complex were feasible in all trial runs. We observed no adverse effects such as adhesions between the adhesive and the renal collecting system or the instruments used. The stone-free rate was 100% and 60% in the bioadhesive and conventional retrieval groups, respectively (p = 0.017). Mean retrieval time was significantly shorter at 10 minutes 33 seconds vs 36 minutes 56 seconds in the bioadhesive group vs the conventional group (p = 0.001). CONCLUSIONS: This novel method involving adhesive based complete removal of residual fragments from the collecting system has proved to be feasible. Our evaluation in a porcine kidney model revealed that this technology performed well. Further tests, including inpatient studies, are required to thoroughly evaluate the benefit and potential drawbacks of bioadhesive based extraction of residual fragments after intracorporeal lithotripsy.