Vaginal Er Research Articles

Defining the Transcriptional Landscapes of the Tumor Microenvironment of Cervical and Vaginal Cancers at Single-Cell Resolution

Malignancies found within vaginal tissue are often diagnosed as cancers of the cervix, vulva, or urethra and are clinically treated with similar modalities. However, the rarity of vaginal cancer may be an artifice of categorization; current treatment paradigms do not take into account tissue-specific mutations and differences in mechanistic pathways intracellularly. Understanding the shared and distinctly different transcriptional profiles of vaginal and cervical tumors at a single-cell resolution will provide insights in vaginal tumor biology and will open avenues for future clinical interventions. Biopsies of tumor and adjacent normal tissue from 9 patients (3 adenocarcinomas (ADC), 3 squamous cell carcinomas (SCC) from the cervix, and 3 vaginal SCC) were collected and analyzed by single-cell RNA sequencing (scRNA-seq) to compare the tumor, immune, and stromal features of cervical and vaginal cancers. Collectively, over 50,000 cells were analyzed by scRNA-seq in this study. We performed dimensionality reduction and clustering analysis of the single-cell transcriptomes to identify the major cell types composing the vaginal and cervical tumor tissues. Compared to Cervical SCC, Vaginal SCC tissues showed reduced fractions of macrophages (-2.7 log2-fold; padj < 0.02) and T cells (-3.7 log2-fold; padj < 0.02) by differential cell proportion analysis (RAISIN). Likewise, the vaginal SCC epithelial cell compartments showed downregulation of inflammatory pathways including TNF signaling via NFKB (NES = -5.7, padj = 5.0 × 10-19), IL2 STAT5 signaling (NES = -4.5, padj = 1.6 × 10-12), and interferon gamma response (NES = -4.3, padj = 9.4 × 10-12), among the Hallmark pathway collection. On the other hand, vaginal SCC epithelial cells showed significant upregulation of oxidative phosphorylation (NES = 4.8, padj = 1.7 × 10-17), p53 pathway (NES = 4.2, padj = 1.8 × 10-13), mTORC1 signaling (NES = 4.2, padj = 1.9 × 10-13), and estrogen early and late response (NES = 4.0, padj < 7.5 × 10-12) compared to cervical SCC. These results highlight distinct differences in the cell type composition and cancer epithelial pathways in vaginal vs. cervical SCC. Among upregulated pathways in vaginal SCC, ER and mTORC1 pathway activation may represent targets for therapeutic intervention worthy of further investigation.

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application.

In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically. On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index = VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing. Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day a few white macroscopic foci were visible and an increase in pH was measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in the laser group. In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls.

Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial.

To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. KU Leuven, Belgium. Twenty-four ewes. Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7days after the third application (69% and 67%, respectively, both P<0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P<0.0001) and higher vaginal compliance (P<0.05). None of the interventions induced changes in the lamina propria. Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT.

Vaginal therapy of mild and moderate stress urinary incontinence using Er:YAG laser: a real treatment option.

To evaluate the effectiveness of vaginal Er:YAG laser as treatment in patients with mild or moderate stress urinary incontinence. The study was a prospective, non-randomised, single center study of 33 women treated with two Er:YAG laser applications on an interval of four weeks. Follow-up evaluations were performed 4 and 8 weeks and 6 months after the first vaginal Er:YAG laser application (4 weeks and 5 months after the second vaginal Er:YAG laser application, respectively). The subjective outcomes were assessed using the International Consultation of Incontinence Modular Questionnaire Short Form (ICIQ-SF) and medical history. Patients rated their quality of life on a scale from 0 to 10. The average quality of life (QoL) showed a significant improvement 5 months after both Er:YAG laser applications. The mean QoL score was 6.0 (SD 2.4) and improved to a mean of 7.6 (SD 1.8) (p = 0.004). The mean ICIQ-SF score changed significantly from 12.3 (SD 3.2, median 13, range 8-18) before treatment to 6.8 (SD 4.0, median 7, range 0-15) 6 months after treatment (p <0.001). 24 patients out of 32 (75%) would again choose to have this therapy performed and 25 patients of 32 (78%) would recommend the vaginal Er:YAG laser therapy to a friend. The rate of side effects was low and none of the patients needed a medical treatment. This study confirms that vaginal Er:YAG therapy can improve clinical and quality of life outcomes in patients with SUI.

Effect of Er:YAG Laser for Women with Stress Urinary Incontinence

Purpose The aim of our study is to assess efficacy of noninvasive erbium-doped yttrium aluminium garnet laser (Er:YAG laser) for female stress urinary incontinence (SUI). Materials and Methods Forty-one women with SUI were included in the study and scheduled for vaginal Er:YAG laser treatment. The procedure was performed with a 2940 nm, Er:YAG laser (Fotona Smooth ™ XS, Fotona, Ljubljana, Slovenia), designed to heat up the vaginal mucosa to around 60°C. All subjects had a baseline and 6 months' posttreatment assessment that included perineal sonography and lower urinary tract symptoms. Results Significant improvements in both urinary frequency and incontinence were found 6 months after Er:YAG laser treatment when compared to the baseline results (p<0.001). The battery of questionnaires administered to patients, including the UDI-6, IIQ-7, OABSS, and POPDI-6, all showed significant improvement posttreatment (P < 0.001). The treatment efficacy for the vaginal Er:YAG laser for SUI at 6 months posttreatment was 75.5% (31/41). Bladder neck mobility by perineal ultrasonography decreased significantly (16.1 ± 6.4 mm to 10.5 ± 4.6 mm) after treatment (p=0.039). No permanent adverse events were found. Conclusions The Er:YAG vaginal laser seems to be a safe and efficacious treatment for women with mild to moderate SUI, this being partly related to the decrease of bladder neck mobility following laser treatment.

Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment

First evaluation of dual-phase vaginal Er:YAG laser to omit hormonal treatment for atrophy-related symptoms in post-menopausal breast cancer survivors following prolapse surgery. Patients with a history of breast cancer at the time of surgery for pelvic organ prolapse were offered non-hormonal vaginal Er:YAG laser treatment when complaining of atrophy-related genitourinary syndrome of menopause. A single 10-min course of dual-phase protocol of pulsed Er:YAG laser (2940nm, fractional ablative and thermal mode, fluence according to tissue thickness). Follow-up included subjective satisfaction, vaginal pH, vaginal health index (VHI), and complications after 6weeks. A total of 16 breast cancer survivors (age 71years, SD 7) had been seeking treatment for pelvic floor symptoms related to vaginal atrophy at follow-up visits after prolapse surgery. All ablative vaginal Er:YAG laser outpatient procedures were successfully completed, all patients returned to daily activities without a need for analgetic medication. Evaluation was performed after 8.3 (SD 2.5) weeks. Pre-laser VHI scored 16 (SD 4.6) and post-laser VHI 20 (SD 3) with p = 0.01. Patients were satisfied in 94% (n = 15) regarding symptom relief. Breast cancer survivors with atrophy-related complaints after pelvic floor surgery may benefit from vaginal application of this innovative dual protocol of Er:YAG laser technology as a non-hormonal treatment approach.

P-974: Characterization of human semen electrical resistance (ER) using the Fertilitrac© ovulation predictor device

The Biosense Fertilitrac © fertility monitor is an intravaginal personal medical device that measures electrical resistance (in ohms) of the vaginal epithelium. It is presently in clinical trials to assess its utility for predicting ovulation in women. We observed that presence of semen in the vagina following intercourse causes spikes in vaginal ER measurements. This may lead to bias in prediction of ovulation especially in couples who are advised to have intercourse at regular intervals to achieve a pregnancy.