Light and energy-based therapeutics for genitourinary applications: Consensus on protocols and best practices.

BACKGROUND: Lasers and energy-based technologies have been developed for genitourinary applications over the past several decades. AIMS: This consensus article aims to categorize the published articles and clinical trial data that culminated in protocol development of technology for genitourinary applications, and to develop consistent parameters in future clinical trials. MATERIALS AND METHODS: The published articles and clinical trials data on lasers and energy-based devices applied to genitourinary conditions were categorized according to device and condition and consensus developed on protocols and parameters. RESULTS: The devices in genitourinary applications were classified as fractional lasers, radiofrequency and high-intensity focused electromagnetic field therapy. The consensus of the protocols and parameters based upon the published clinical trials of their application to the vaginal and urologic conditions associated with genitourinary syndrome of menopause was developed and organized according to device and condition. DISCUSSION: The status of FDA clearances and future pathways are discussed. CONCLUSIONS: This consensus article categorizes and presents the protocols and practices for the main classes of lasers and energy-based devices for genitourinary applications in future clinical trials.

Nickel-induced alterations to chromatin structure and function.

Nickel (Ni), a heavy metal is prevalent in the atmosphere due to both natural and anthropogenic activities. Ni is a carcinogen implicated in the development of lung and nasal cancers in humans. Furthermore, Ni exposure is associated with a number of chronic lung diseases in humans including asthma, chronic bronchitis, emphysema, pulmonary fibrosis, pulmonary edema and chronic obstructive pulmonary disease (COPD). While Ni compounds are weak mutagens, a number of studies have demonstrated the potential of Ni to alter the epigenome, suggesting epigenomic dysregulation as an important underlying cause for its pathogenicity. In the eukaryotic nucleus, the DNA is organized in a three-dimensional (3D) space through assembly of higher order chromatin structures. Such an organization is critically important for transcription and other biological activities. Accumulating evidence suggests that by negatively affecting various cellular regulatory processes, Ni could potentially affect chromatin organization. In this review, we discuss the role of Ni in altering the chromatin architecture, which potentially plays a major role in Ni pathogenicity.

Vaginal erbium laser for treatment of stress urinary incontinence: optimization of treatment regimen for a sustained long-term effect.

Stress urinary incontinence (SUI) is a common health problem that affects roughly 35% of women in the reproductive period. A prospective uncontrolled study was conducted to assess the long-term efficacy and safety of a non-ablative Er:YAG laser treatment of SUI. Forty-three patients participated in the study. All women underwent three sessions of IncontiLase® procedure, and efficacy of laser treatment was assessed by 1-h pad test, 24-h pad test, 3-day voiding diary, and ICIQ-UI SF questionnaire at multiple follow-ups. Statistical analysis was performed using one-way repeated measures ANOVA. Patients were questioned about discomfort during treatment and any adverse events following the laser procedures. All outcome measures showed a significant change over a period of the entire clinical trial. Eighteen-month follow-up revealed a fading of the effect, which was alleviated by single-session maintenance treatments every 6 months. There were no serious adverse events reported during the study. All reported side effects were mild and transient. The application of non-ablative Er:YAG laser for SUI treatment significantly improves the SUI symptoms. High improvement rates and patient satisfaction can be maintained with single-session maintenance treatments performed every 6 months. Long-term safety profile of multiple non-ablative Er:YAG laser treatment is shown. NCT04348994, 16.04.2020, retrospectively registered.

Nonablative transurethral Erbium:YAG laser treatment for chronic prostatitis/chronic pelvic pain syndrome: A prospective comparative study.

AIMS: This prospective study aimed to compare the clinical outcomes between the use of Erbium:YAG (Er:YAG) laser in a nonablative mode, to the use of the pharmacological treatment of oral tadalafil for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: The laser group received two sessions of Erbium:YAG laser, administered intraurethrally in a long, nonablative train of long pulses (SMOOTH™ mode), applied at the level of the male prostatic urethra. Tadalafil group received oral tadalafil at a dose of 5 mg/day, consecutively for 2 months. Effectiveness was assessed using the International Prostate Symptom Score (IPSS) questionnaire, VAS (visual analogue scale) pain score, and maximum urethral flow at follow-up visits up to 12 months after initiating treatment. Adverse effects were recorded after each treatment and follow-up sessions. RESULTS: The results show a significant decrease in the IPSS score in both groups up to the 12-month follow-up. The increase in Q-max was evident up to 3-months follow-up in the tadalafil group and up to 6 months in the laser group. The decrease in the VAS pain score was also significant in both treatment groups, lasting up to 3 months in the tadalafil group and up to 6 months in the laser group. CONCLUSIONS: The nonablative Er:YAG SMOOTH™ laser seems to be a promising treatment for this widely occurring condition. More studies are needed to confirm its safety and efficacy.

Intraurethral Erbium:YAG laser for the management of urinary symptoms of genitourinary syndrome of menopause: A pilot study.

OBJECTIVES: Genitourinary syndrome of menopause (GSM) combines the conditions of vulvovaginal atrophy (VVA) and urinary tract dysfunction, which is a result of urethral atrophy. There are several treatment methods available for the management of vulvovaginal symptoms of GSM, whereas urinary tract dysfunction often remains overlooked and undertreated. The objective of this pilot study was to assess the safety and efficacy of intraurethral Er:YAG laser treatment of urinary symptoms of GSM. PATIENTS AND METHODS: Patients with diagnosed GSM, having less than 5% of vaginal superficial cells in the cytology, vaginal pH higher than 5, with urinary symptoms of GSM (dysuria, frequency, urgency) and impaired continence due to urethral atrophy, received two sessions of intraurethral Er:YAG laser with a 3-week interval in-between the sessions. Laser energy was delivered in non-ablative way using Erbium SMOOTH™ mode technology and a 4-mm thick cannula. Therapeutic efficacy was determined using ICIQ-SF, the 1-hour pad test and VAS scores. Occurrence of adverse effects was followed at every visit. Follow ups (FU) were at 3 and 6 months. RESULTS: 29 female patients fulfilling the inclusion criteria were included in this pilot study and received two sessions of the intraurethral non-ablative Erbium SMOOTH™ laser therapy. Significant improvement was observed in all measured parameters at both FU. ICIQ-SF improved by an average of 64% at 3 months FU and by 40% at 6 months. The 1-hour pad test showed a reduction of the quantity of leaked urine by 59% at 3 months FU and by 42% at 6 months FU. All urinary symptoms of GSM improved. Dysuria dropped to 13% and 31% of baseline values at three and 6 months respectively, urinary urgency dropped to 23% and 47% and frequency dropped to 22% and 43% after 3 and 6 months, respectively. Adverse effects were mild and transient. CONCLUSIONS: Our findings suggest that intraurethral Er:YAG laser is an efficacious and safe modality for treatment of urinary symptoms of GSM, however, prospective, randomized, and controlled trials with larger number of patients are needed to better assess the long-term effect of this novel procedure. Lasers Surg. Med. 50:802-807, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Efficacy of Erbium:YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause.

OBJECTIVES: The objective of this prospective comparative cohort study was to establish the effectiveness and safety of Erbium:YAG (Er:YAG) laser treatment for genitourinary syndrome of menopause and to compare it with an established topical estriol treatment. METHODS: Fifty patients with genitourinary syndrome of menopause were divided into two groups. The estriol group received a treatment of 0.5 mg estriol ovules for 8 weeks and the laser group was first treated for 2 weeks with 0.5 mg estriol ovules 3 times per week to hydrate the mucosa and then received three sessions with 2,940 nm Er:YAG laser in non-ablative mode. Biopsies were taken before and at 1, 3, 6, and 12 months post-treatment. Maturation index, maturation value and pH where recorded up to 12-months post-treatment, while the VAS analysis of symptoms was recorded up to 18 months post-treatment. RESULTS: Statistically significant (P < 0.05), reduction of all assessed symptoms was observed in the laser group at all follow-ups up to 18 months post-treatment. Significant improvement in maturation value and a decrease of pH in the laser group was detected up to 12 months after treatment. The improvement in all endpoints was more pronounced and longer lasting in the laser group. Histological examination showed changes in the tropism of the vaginal mucosa and also angiogenesis, congestion, and restructuring of the lamina propria in the laser group. Side effects were minimal and of transient nature in both groups, affecting 4% of patients in the laser group and 12% of patients in the estriol group. CONCLUSIONS: Our results show that Er:YAG laser treatment successfully relieves symptoms of genitourinary syndrome of menopause and that the results are more pronounced and longer lasting compared to topical estriol treatment. Lasers Surg. Med. 49:160-168, 2017. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Light and energy based therapeutics for genitourinary syndrome of menopause: Consensus and controversies.

Gynecologist and plastic surgeons pioneered the application of lasers in medicine and surgery almost 5 decades ago, initially used to treat cervical and vaginal pathologies. Ever since, energy-based devices have been deployed to treat pelvic pathologies and improve fertility. Recent technological developments triggered an unprecedented wave of publications, assessing the efficacy of fractional laser, and radiofrequency on the vaginal wall in reversing natural aging processes. Studies have shown that a certain degree of thermal energy deposited on the vaginal wall stimulates proliferation of the glycogen-enriched epithelium, neovascularization, and collagen formation in the lamina propria, and improves natural lubrication and control of urination. This review aimed to review such data and to guide future research. A unique assembly of experts from around the globe, compiled and edited this manuscript based on a thorough literature review and personal experience. Lasers Surg. Med. 49:137-159, 2017. © 2017 Wiley Periodicals, Inc.

Non-ablative erbium YAG laser for the treatment of type III stress urinary incontinence (intrinsic sphincter deficiency).

The objective of this pilot study was to determine the safety and efficacy of a new non-ablative erbium YAG laser procedure for the treatment of type III stress urinary incontinence (intrinsic sphincter deficiency) in women. Twenty-two patients with a Valsalva leak point pressure less than 60 cm H2O were recruited and treated with a non-ablative erbium laser delivering low fluence pulses inside the whole length of the urethra through a specially designed cannula. Treatment consisted of two treatment sessions with a 3-week interval in-between. Therapeutic efficacy, as assessed by a questionnaire addressing quality of life during urinary incontinence and the 1-h pad test, was measured at 3 and 6 months after the procedure. Both methods of assessment showed similar levels of improvement in terms of incontinence severity and improvement in quality of life. All patients tolerated the therapy well and adverse effects were mild and transient. The results of this pilot study showed significant improvement of type III stress urinary incontinence. Despite the limitations of this study, being small patient number and short follow-up, this non-ablative intraurethral erbium YAG laser procedure seems to be a safe and efficacious alternative for patients with type III stress urinary incontinence. More controlled studies should be performed to confirm this data and to evaluate the long-term effects.

Superficial dyspareunia treatment with hyperstacking of erbium:yttrium-aluminum-garnet SMOOTH laser: a short-term, pilot study in breast cancer survivors.

OBJECTIVE: This prospective pilot study aimed to evaluate the effects of a modified vaginal erbium laser (VEL) protocol, using the hyperstack mode on the vaginal vestibulum and introitus to treat superficial dyspareunia in postmenopausal breast cancer survivors suffering from the genitourinary syndrome of menopause. METHODS: In this pilot, prospective, randomized study, two groups of postmenopausal women suffering from superficial dyspareunia were included: 34 women (VEL group) were treated with erbium laser crystal yttrium-aluminum-garnet (XS Fotona SMOOTH; Fotona, Ljubljana, Slovenia) with a wavelength of 2,940 nm; for the other 34 (hyperstack group), a modified second step of the VEL protocol for the treatment of vestibulum and introitus was used, with hyperstacked (repeating a number of) subablative, long pulses with very low fluences. For each group, three laser applications at 30-day intervals were performed. Symptoms were assessed before, after each application, and after 1 and 3 months from the last laser application, using the visual analog scale score for superficial dyspareunia. RESULTS: Superficial dyspareunia improved in both groups over time (P < 0.001), regardless of age and years since menopause status. The reduction in visual analog scale score after the third laser application was 58% in VEL versus 73.5% in hyperstack. The hyperstack group, since the first laser application, showed a greater (P < 0.001) and persistent improvement of superficial dyspareunia. CONCLUSIONS: The hyperstack treatment of the introitus and vestibulum in breast cancer survivors leads to a more significant improvement in superficial dyspareunia than the VEL alone.

Long-Term Improvement in Urinary Incontinence in an Elite Female Athlete Through the Laser Treatment: A Case Report.

Stress urinary incontinence (SUI) is increasing in elite female athletes (EFAs), affecting competition results and quality of life. Pelvic floor muscle training (PFMT) is the first-line treatment for SUI, and surgery is generally performed when PFMT is insufficient. However, in EFA, there are few cases in which surgery is performed and fewer reports. Therefore, there is no known general treatment strategy for EFA with SUI. In our study, a 23-year-old track-and-field medalist with severe SUI was successfully treated with a vaginal and urethral erbium-doped yttrium aluminum garnet laser (VEL + UEL). After 12 treatments over one year, urinary incontinence decreased from 300 mL or more in the 400 m track run before treatment to 0 mL. She did not experience any more problems during running or competition. There was no recurrence of SUI for three years, and the urethral pressure profile examination confirmed improvement. MRIs showed that the left puborectalis muscle was absent from the first visit. The urethra was oval with an anteroposterior outer diameter of 10 mm and a transverse outer diameter of 13 mm before treatment. However, after three years of treatment, both anteroposterior and transverse diameters became circular, measuring 11 mm. Vaginal wall thickness increased from 8 to 12 mm at the center of the height of the urethra, making it possible to support the urethra, and pretreated adipose tissue space between the urethra and vagina disappeared. It was noted that the uneven and fragile urethra/vagina, the presence of adipose tissue space, and the absence of the left puborectalis muscle may have been the cause of the SUI. One year of VEL + UEL treatment resulted in long-term improvement of SUI; MRI showed changes in the urethra and vagina.