Prospective non-randomized comparison of transurethral laser en bloc resection vs. conventional resection of bladder tumors larger than 3 cm.

BACKGROUND: En bloc resection of bladder tumor (ERBT) is an established surgical treatment method for patients with non-muscle invasive bladder cancer (NMIBC) in tumors less than 3 cm. Data regarding the efficacy and safety of ERBT on larger than 3 cm tumors are sparse and its efficacy compared to conventional transurethral resection (TURBT) remains unclear. The aim of this study was to prospectively compare the feasibility, safety and oncological outcomes of laser (Tm-fiber) ERBT and TURBT in patients with primary bladder lesions ≥3 cm. METHODS: A cohort of 45 patients who underwent surgery for primary NMIBC between February 2018 and March 2022 was collected prospectively. There was no randomization. All procedures were performed by two experienced surgeons. Inclusion criteria were as follows: age >18 years, primary Ta or T1 bladder tumor with a diameter of ≥3 cm, no more than 3 tumors and no history of upper tract urothelial carcinoma. Exclusion criteria were carcinoma in situ or invasion into muscle layer (≥T2). ERBT was performed with thulium fiber laser (IPG, Russia). Primary endpoints included efficacy with recurrence-free survival (RFS) at 3, 6 and 12 months. Secondary endpoints were safety parameters, perioperative data and specimen quality (the presence of muscle layer in specimens). RESULTS: Twenty-eight patients underwent laser ERBT and 17 conventional TURBT. The location and size of the tumors were comparable in both groups. The success rate was 93.3% in the ERBT group with two cases of conversion from ERBT to TURBT. Detrusor muscle was present in 92.8% patients in the ERBT group versus 70.5% in the TURBT group (P=0.04). Obturator nerve reflex was observed only in the TURBT group: 17.6% vs. 0.0% (P=0.02). The frequency of other complications was comparable between the two groups. RFS was not statistically different between the two methods at 3 (93.9% vs. 94.1%, P=0.87), 6 (89.3% vs. 82.3%, P=0.5) and 12 months (89.3% vs. 70.6%, P=0.11). CONCLUSIONS: Laser ERBT is a feasible and safe procedure to manage bladder tumors larger than 3 cm. While it seems safer than TURBT, its effect on efficacy remains to be assessed in larger trials.

Randomized prospective trial of the severity of irritative symptoms after HoLEP vs ThuFLEP.

PURPOSE: To compare the short-term postoperative functional outcomes and severity of irritative symptoms following holmium and thulium fiber laser enucleation (HoLEP and ThuFLEP). METHODS: This prospective randomized single-blinded study was performed in accordance with CONSORT. The inclusion criteria were IPSS > 20 or Qmax < 10 ml/s. Patients were randomized between HoLEP and ThuFLEP. Demographics, objective data (PSA, prostate volume, etc.), data on urinary and sexual function (IPSS, IIEF, QoL, QUID, Qmax, ICIQ-MLUTS) were collected. Detailed perioperative information and postoperative data on functional outcomes at 1, 2, 3, 4, 6, 8, 10, 12 weeks and 6 months were collected. RESULTS: Data on 163 participants were included (77-HoLEP, 86-ThuFLEP). No differences were found in surgery duration; number of postoperative complications (Clavien-Dindo I-III), catheterization time and hospital stay. Functional outcomes up to 6 months didn't differ between the groups (IPPS, IIEF, QoL, QUID, ICIQ-MLUTS, Qmax, p > 0.05). Total ICIQ-MLUTS, bother and voiding scores at 1 and 3 months significantly increased compared with the baseline in both groups (p < 0.05). No difference between the groups were observed. In HoLEP the SUI series rate was 1.3% and 1.3% after 3 and 6 months following the procedure; in ThuFLEP: it was 3.5% and 2.3% respectively (p = 0.35 and p = 0.54). CONCLUSION: The preliminary results of the study showed no apparent differences in functional outcomes (IPSS, Qmax), rate of SUI or irritative symptoms. Both ThuFLEP and HoLEP are efficient ways of treating benign prostatic obstruction. Both surgeries are comparable in terms of duration and postoperative complication rates.

Thulium Fiber Laser Enucleation of the Prostate: Prospective Study of Mid- and Long-Term Outcomes in 1328 Patients.

Objective: The objective of our study was to estimate the long-term efficacy and safety of thulium fiber laser enucleation of the prostate (ThuFLEP). Materials and Methods: We analyzed patients who underwent ThuFLEP due to lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). Both the pre- and perioperative data as well as the follow-up data for 3 years were evaluated: prostate volume, postvoid residual (PVR), maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), quality of life (QoL), prostate-specific antigen level, and the complication rate. Intraoperative data relating to the weight of resected tissue, the duration of surgery, catheterization, and data on hospital stays were also collected. A subgroup analysis was performed to assess whether older patients (>65 years) or those with larger glands (>80 cc) are prone to increased complication risks. Results: A total of 1328 patients were included in the analysis. The mean age was 66.9 ± 7.5 years. Mean prostate volume was 86.9 ± 41.9 (20-330) cc. All the functional parameters (IPSS, QoL, PVR, Qmax) significantly improved after surgery (p < 0.05) and showed durable improvement up to 3 years of follow-up. The frequency of late complications was as follows: stress urinary incontinence-1.2%; urethral stricture-1.1%; and bladder neck contracture-0.9%. Subgroup analyses revealed increased urinary tract infection frequency in older patients (3.5% vs 0.8%, p = 0.003) as well as higher rate of stress urinary incontinence (0.4% vs 1.8%, p = 0.002) and higher rate of clot retention (11.3% vs 4.4%, p < 0.001) in those with larger glands. Conclusions: Irrespective of the patient's age and prostate volume, ThuFLEP represents an effective and durable technique of endoscopic enucleation characterized by a low incidence of complications after 3 years of follow-up. In the hands of an experienced surgeon, ThuFLEP can rightly be a promising alternative to holmium laser enucleation of the prostate for treatment of LUTS associated with BPO.

EAU, AUA and NICE Guidelines on Surgical and Minimally Invasive Treatment of Benign Prostate Hyperplasia: A Critical Appraisal of the Guidelines Using the AGREE-II Tool.

OBJECTIVE: To critically appraise the methodological rigour of the clinical practice guidelines (CPGs) vis-à-vis BPH surgery as used by specialist research associations in the US, Europe and UK, and to compare whether the guidelines cover all or only some of the available treatments. METHODS: The current guidelines issued by the EUA, AUA and NICE associations have been analyzed by 4 appraisers using the AGREE-II instrument. We also compared the recommendations given in the guidelines for surgical and minimally invasive treatment to find out which of these CPGs include most of the available treatment options. RESULTS: According to the AGREE II tool, the median scores of domains were: domain 1 scope and purpose 66.7%, domain 2 stakeholder involvement 50.0%, domain 3 rigor of development 65.1%, domain 4 clarity of presentation 80.6%, domain 5 applicability 33.3%, domain 6 editorial independence 72.9%. The overall assessment according to AGREE II is 83.3%. The NICE guideline scored highest on 5 out of 6 domains and the highest overall assessment score (91.6%). The EAU guideline scored lowest on 4 out of 6 domains and has the lowest overall assessment score (79.1%). CONCLUSIONS: The analyzed CPGs comprehensively highlight the minimally invasive and surgical treatment options for BPH. According to the AGREE II tool, the domains for clarity of presentation and editorial independence received the highest scores. The stakeholder involvement and applicability domains were ranked as the lowest. Improving the CPG in these domains may help to improve the clinical utility and applicability of CPGs.

Modeling Hepatotropic Viral Infections: Cells vs. Animals.

The lack of an appropriate platform for a better understanding of the molecular basis of hepatitis viruses and the absence of reliable models to identify novel therapeutic agents for a targeted treatment are the two major obstacles for launching efficient clinical protocols in different types of viral hepatitis. Viruses are obligate intracellular parasites, and the development of model systems for efficient viral replication is necessary for basic and applied studies. Viral hepatitis is a major health issue and a leading cause of morbidity and mortality. Despite the extensive efforts that have been made on fundamental and translational research, traditional models are not effective in representing this viral infection in a laboratory. In this review, we discuss in vitro cell-based models and in vivo animal models, with their strengths and weaknesses. In addition, the most important findings that have been retrieved from each model are described.

Fibrin-based Bioinks: New Tricks from an Old Dog.

For the past 10 years, the main efforts of most bioprinting research teams have focused on creating new bioink formulations, rather than inventing new printing set-up concepts. New tissue-specific bioinks with good printability, shape fidelity, and biocompatibility are based on "old" (well-known) biomaterials, particularly fibrin. While the interest in fibrin-based bioinks is constantly growing, it is essential to provide a framework of material's properties and trends. This review aims to describe the fibrin properties and application in three-dimensional bioprinting and provide a view on further development of fibrin-based bioinks.

Long-Term Outcomes of Holmium Laser Enucleation of the Prostate: A 5-Year Single-Center Experience.

Objective: To analyze the long-term efficacy and safety of holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia. Materials and Methods: A total of 127 patients who underwent HoLEP at our institution between 2013 and 2015 were included. Patients were observed for 5 years postoperatively. We evaluated the length of the surgery, the mass of the removed tissue, prostate-specific antigen level, the maximal flow rate (Qmax), postvoid residual (PVR), the length of catheterization and hospitalization, and the International Prostate Symptom Score (IPSS) and IPSS quality of life (QoL) at each clinic visit. Results: PVR, Qmax, IPSS, and QoL all improved significantly immediately after the operation (p < 0.001). By the end of the 5th postoperative year, all the parameters showed a statistically meaningful decline: Qmax reduced by 5.8 mL/s (22.6%) and IPSS by 1.4 points (29.1%). Around 8.6% of the patients continued therapy with α-blockers. There were no differences in efficacy by the age of the patients or the volume of the prostate. Long-term complications and need for repeat operations were not affected by the volume of the prostate or patient age. Conclusions: The improvement of PVR, Qmax, IPSS, and QoL score seen in the early postoperative period after performing HoLEP remains evident at 5 years postoperatively. Long-term complications and the need for reoperation do not depend on the age of the patient or on the initial volume of the prostate.

Analysis of Learning Curve in Robot-Assisted Radical Prostatectomy Performed by a Surgeon.

This study aimed to report the learning curve in robot-assisted radical prostatectomy (RARP) performed by one surgeon who is experienced in laparoscopic prostatectomies. The records of 145 RARP cases performed between 2015 and 2017 were evaluated retrospectively. Patients were divided into three groups: group 1 comprised the first 49 cases, group 2 comprised 50-88 cases, and the rest of the cases were assigned to group 3. Continence was defined as the necessity to use at least one pad during a day. Additionally, erectile function recovery was defined as having erection sufficient for sexual intercourse regardless of using a phosphodiesterase type 5 inhibitor. Continence and erectile function recovery were assessed during interviews at 3, 6, and 12 months after surgery. First, all procedures were successfully performed without conversions or blood transfusions. The median follow-up period was 22 months. Moreover, the median skin-to-skin operative time (OT) was 220 minutes. The median blood loss was 150 ml, and the mean hospital stay was 8.9 ± 3.87 days. The median prostate volume was 36 cm³. The overall positive surgical margin rate was 13.1%. Overall, 38 (26.2%) postoperative complications were observed, and 17.9% of them were graded as minor. Anastomotic leakage decreased significantly from group 1 to group 3 (26.5% and 7%, respectively). The continence recovery (0-1 pad) rates were 60.6%, 75.7%, and 84.9% at 3, 6, and 12 months after surgery, respectively. Subsequently, the erectile function recovery rates were 50.9% and 65.4% at 6 and 12 months after surgery, respectively. In conclusion, there are several types of learning curves for RARP. First, the shallowest learning curve was observed for the OT. Regarding the analysis of "advanced learning curve," demonstrating the improvement of OT and blood loss is considered insufficient. Therefore, additional oncological and functional results that require a longer period of investigation are required.

Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches.

Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, the delivery of a therapeutic gene into target cells via AAV represents a major obstacle in the field. Ideally, transgenes should be delivered into the target cells specifically and efficiently, while promiscuous or off-target gene delivery should be minimized to avoid toxicity. In the pursuit of an ideal vehicle for NDD gene therapy, a broad variety of vector systems have been explored. Here we specifically outline the advantages of adeno-associated virus (AAV)-based vector systems for NDD therapy application. In contrast to many reviews on NDDs that can be found in the literature, this review is rather focused on AAV vector selection and their preclinical testing in experimental and preclinical NDD models. Preclinical and in vitro data reveal the strong potential of AAV for NDD-related diagnostics and therapeutic strategies.

Skin tissue regeneration for burn injury.

The skin is the largest organ of the body, which meets the environment most directly. Thus, the skin is vulnerable to various damages, particularly burn injury. Skin wound healing is a serious interaction between cell types, cytokines, mediators, the neurovascular system, and matrix remodeling. Tissue regeneration technology remarkably enhances skin repair via re-epidermalization, epidermal-stromal cell interactions, angiogenesis, and inhabitation of hypertrophic scars and keloids. The success rates of skin healing for burn injuries have significantly increased with the use of various skin substitutes. In this review, we discuss skin replacement with cells, growth factors, scaffolds, or cell-seeded scaffolds for skin tissue reconstruction and also compare the high efficacy and cost-effectiveness of each therapy. We describe the essentials, achievements, and challenges of cell-based therapy in reducing scar formation and improving burn injury treatment.

Collagen fibrillar structures in vocal fold scarring and repair using stem cell therapy: a detailed histological, immunohistochemical and atomic force microscopy study.

Regenerative medicine opens new opportunities in the repair of cicatricial lesions of the vocal folds. Here, we present a thorough morphological study, with the focus on the collagen structures in the mucosa of the vocal folds, dedicated to the effects of stem cells on the vocal folds repair after cicatricial lesions. We used a conventional experimental model of a mature scar of the rabbit vocal folds, which was surgically excised with a simultaneous implantation of autologous bone marrow-derived mesenchymal stem cells (MSC) into the defect. The restoration of the vocal folds was studied 3 months postimplantation of stem cells and 6 months after the first surgery. The collagen structure assessment included histology, immunohistochemistry and atomic force microscopy (AFM) studies. According to the data of optical microscopy and AFM, as well as to immunohistochemical analysis, MSC implantation into the vocal fold defect leads not only to the general reduction of scarring, normal ratio of collagens type I and type III, but also to a more complete restoration of architecture and ultrastructure of collagen fibres in the mucosa, as compared to the control. The collagen structures in the scar tissue in the vocal folds with implanted MSC are more similar to those in the normal mucosa of the vocal folds than to those of the untreated scars. AFM has proven to be an instrumental technique in the assessment of the ultrastructure restoration in such studies. LAY DESCRIPTION: Regenerative medicine opens new opportunities in the repair of the vocal fold scars. Because collagen is a main component in the vocal fold mucosa responsible for the scar formation and repair, we focus on the collagen structures in the mucosa of the vocal folds, using a thorough morphological study based on histology and atomic force microscopy (AFM). Atomic force microscopy is a scanning microscopic technique which allows revealing the internal structure of a tissue with a resolution up to nanometres. We used a conventional experimental model of a mature scar of the rabbit vocal folds, surgically excised and treated with a mesenchymal stem cells transplant. Our morphological study, primarily AFM, explicitly shows that the collagen structures in the scarred vocal folds almost completely restore after the stem cell treatment. Thus, the modern microscopic methods, and especially AFM are instrumental tools for monitoring the repair of the vocal folds scars.

Author Correction: Optimization of Photosensitized Tryptophan Oxidation in the Presence of Dimegin-Polyvinylpyrrolidone-Chitosan Systems.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Risk factors for urethral stricture and/or bladder neck contracture after monopolar transurethral resection of the prostate for benign prostatic hyperplasia.

OBJECTIVE:: To identify risk factors for urethral stricture and/or bladder neck contracture after transurethral resection of benign prostatic hyperplasia. MATERIALS AND METHODS:: We performed a retrospective analysis of 402 patients, which underwent a monopolar transurethral resection of the prostate in the urology clinic of Sechenov First Moscow State Medical University for prostatic hyperplasia during the period 2011-2014. Urethral stricture and (or) bladder neck contracture in the postoperative period were diagnosed in 61 (15.27%) patients; 34 patients (8.6%) had urethral stricture, 20 (4.97%) bladder neck contracture, and 7 (1.7%) had a combination of urethral stricture and bladder neck contracture. In 341 of cases (84.73%), no late postoperative complications were observed. A total of 106 of the 341 patients met the inclusion criteria, hence, containing all the information necessary for analysis such as the volume of the prostate, the duration of the surgery, the size of the endoscope, data on concomitant diseases, analysis prostatic secretion, and so on. Thus, two groups were formed. Group 1 (106 patients) is the control group in which urethral strictures and/or bladder neck contractures did not occur in the long-term postoperative period and group 2 (61 patients), in which was observed the formation of these complications. To calculate the statistical significance of the differences for categorical data, Fisher criterion was used. For quantitative variables, in the case of normal data distribution, an unpaired t-test or one-way analysis of variance was used; for data having a distribution different from normal, a Mann-Whitney rank test was used. RESULTS:: Regression analysis established the significance of the influence of four factors on the development of scar-sclerotic changes of urethra and bladder neck: the tool diameter 27 Fr ( p < 0.0001), presence of prostatitis in past medical history ( p < 0.0001), prostate volume ( p = 0.003), and redraining of the bladder ( p = 0.0162). CONCLUSION:: The relationship between the diameter of the instrument, presence of chronic prostatitis in anamnesis, increased volume of the prostate, and repeated drainage of the bladder using the urethral catheter with the risk of developing scar-sclerotic changes in the urethra and/or bladder neck are statistically reliable and confirmed as a result of regression analysis.

Impact of endoscopic enucleation of the prostate with thulium fiber laser on the erectile function.

BACKGROUND: The impact of number of endoscopic enucleation of the prostate techniques (holmium laser enucleation - HoLEP for example) on erectile function have already been investigated. However, the thulium-fiber laser, in this setting remains unstudied. In this study, we compared sexual function outcomes in patients with benign prostatic hyperplasia (BPH) treated with transurethral resection of the prostate (TURP) or thulium-fiber laser enucleation (ThuFLEP). METHODS: We performed a retrospective analysis of patients who underwent transurethral resection and endoscopic enucleation of the prostate for BPH; inclusion criteria was the presence of infravesical obstruction (IPSS > 20, Qmax < 10 mL/s). Erectile function (EF) was assessed using the International Index of Erectile Function (IIEF-5) both prior to endoscopic examination, and six months after. RESULTS: A total of 469 patients with BPH were included in the study; of these, 211 underwent to ThuFLEP, and 258 TURP. Preoperative IIEF-5 in TURP and ThuFLEP groups were 11.7 (±4.5) and 11.1 (±5.0), respectively (p = 0.17). At six month the IIEF-5 score was unchanged (p = 0.26 and p = 0.08) and comparable in both groups (p = 0.49). However, mean IIEF-5 score shown significant increase of 0.72 in ThuFLEP group, comparing to decrease of 0.24 in TURP patients (p < 0.001). CONCLUSIONS: Both TURP and ThuFLEP are effective modalities in the management of infravesical obstruction due to BPH. At six months follow-up after surgery, both techniques lead to comparable IIEF-5 score. However, our results demonstrated that the ThuFLEP is more likely to preserve the erectile function leading to increase of IIEF-5 at six months in contrast to TURP which lead to slight drop in IIEF-5 score.

Optimization of Photosensitized Tryptophan Oxidation in the Presence of Dimegin-Polyvinylpyrrolidone-Chitosan Systems.

By the example of a model process of tryptophan photooxidation in the aqueous medium in the presence of a three-component photosensitizing complex (porphyrin photosensitizer-polyvinylpyrrolidone- chitosan, PPS-PVP-CT) in the temperature range of 20-40 °Ð¡, we have demonstrated a possibility of modification of such a process by selecting different molar ratios of the components in the reaction mixture. The actual objective of this selection is the formation of a certain PPS-PVP-CT composition in which PVP macromolecules would coordinate with PPS molecules and at the same time practically block the complex binding of PPS molecules with chitosan macromolecules. Such blocking allows utilization of the bactericidal properties of chitosan to a greater extent, since chitosan is known to depress the PPS photosensitizing activity in PPS-PVP-CT complexes when using those in photodynamic therapy (PDT). The optimal composition of photosensitizing complexes appears to be dependent on the temperature at which the PDT sessions are performed. We have analyzed the correlations of the effective rate constants of tryptophan photooxidation with the photophysical characteristics of the formed complexes.