Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.

Young women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH)2D3, reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH)2D3. Treatment with active 1,25(OH)2D3 induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D.

Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder. Forty-four pelvic regions were examined in 30 human cadavers. Gross post-mortem and intra-operative approaches (open anterior abdominal, manual laparoscopic, and robot-assisted) were used. Nerve branch distances and diameters were measured after thorough visual inspection and gentle dissection, so as to not distort tissue. The IHP had between 1 to 4 vesical branches (2.33 ± 0.72, mean ± SD) with average diameters of 0.51 ± 0.06 mm. Vesical branches from the IHP arose from a grossly visible pelvic ganglion in 93% of cases (confirmed histologically). The pelvic ganglion was typically located 7.11 ± 6.11 mm posterolateral to the ureteral orifice in 69% of specimens. With this in-depth characterization, vesical branches from the IHP can be safely located both posterolateral to the ureteral orifice and emanating from a more proximal ganglionic enlargement during surgical procedures.

Sacral Tarlov perineurial cysts: a systematic review of treatment options.

Tarlov perineurial spinal cysts (TCs) are an underrecognized cause of spinal neuropathic symptoms. TCs form within the sensory nerve root sleeves, where CSF extends distally and can accumulate pathologically. Typically, they develop at the sacral dermatomes where the nerve roots are under the highest hydrostatic pressure and lack enclosing vertebral foramina. In total, 90% of patients are women, and genetic disorders that weaken connective tissues, e.g., Ehlers-Danlos syndrome, convey considerable risk. Most small TCs are asymptomatic and do not require treatment, but even incidental visualizations should be documented in case symptoms develop later. Symptomatic TCs most commonly cause sacropelvic dermatomal neuropathic pain, as well as bladder, bowel, and sexual dysfunction. Large cysts routinely cause muscle atrophy and weakness by compressing the ventral motor roots, and multiple cysts or multiroot compression by one large cyst can cause even greater cauda equina syndromes. Rarely, giant cysts erode the sacrum or extend as intrapelvic masses. Disabling TCs require consideration for surgical intervention. The authors' systematic review of treatment analyzed 31 case series of interventional percutaneous procedures and open surgical procedures. The surgical series were smaller and reported somewhat better outcomes with longer term follow-up but slightly higher risks. When data were lacking, authorial expertise and case reports informed details of the specific interventional and surgical techniques, as well as medical, physical, and psychological management. Cyst-wrapping surgery appeared to offer the best long-term outcomes by permanently reducing cyst size and reconstructing the nerve root sleeves. This curtails ongoing injury to the axons and neuronal death, and may also promote axonal regeneration to improve somatic and autonomic sacral nerve function.

Restoring bladder function using motor and sensory nerve transfers: a cadaveric feasibility study.

OBJECTIVE: Bladder dysfunction after nerve injury has a variable presentation, and extent of injury determines whether the bladder is spastic or atonic. The authors have proposed a series of 3 nerve transfers for functional innervation of the detrusor muscle and external urethral sphincter, along with sensory innervation to the genital dermatome. These transfers are applicable to only cases with low spinal segment injuries (sacral nerve root function is lost) and largely preserved lumbar function. Transfer of the posterior branch of the obturator nerve to the vesical branch of the pelvic nerve provides a feasible mechanism for patients to initiate detrusor contraction by thigh adduction. External urethra innervation (motor and sensory) may be accomplished by transfer of the vastus medialis nerve to the pudendal nerve. The sensory component of the pudendal nerve to the genitalia may be further enhanced by transfer of the saphenous nerve (sensory) to the pudendal nerve. The main limitations of coapting the nerve donors to their intrapelvic targets are the bifurcation or arborization points of the parent nerve. To ensure that the donor nerves had sufficient length and diameter, the authors sought to measure these parameters. METHODS: Twenty-six pelvic and anterior thigh regions were dissected in 13 female cadavers. After the graft and donor sites were clearly exposed and the branches identified, the donor nerves were cut at suitable distal sites and then moved into the pelvis for tensionless anastomosis. Diameters were measured with calipers. RESULTS: The obturator nerve was bifurcated a mean ± SD (range) of 5.5 ± 1.7 (2.0-9.0) cm proximal to the entrance of the obturator foramen. In every cadaver, the authors were able to bring the posterior division of the obturator nerve to the vesical branch of the pelvic nerve (located internal to the ischial spine) in a tensionless manner with an excess obturator nerve length of 2.0 ± 1.2 (0.0-5.0) cm. The distance between the femoral nerve arborization and the anterior superior iliac spine was 9.3 ± 1.8 (6.5-15.0) cm, and the distance from the femoral arborization to the ischial spine was 12.9 ± 1.4 (10.0-16.0) cm. Diameters were similar between donor and recipient nerves. CONCLUSIONS: The chosen donor nerves were long enough and of sufficient caliber for the proposed nerve transfers and tensionless anastomosis.

Non-Surgical Management of Chronic Pelvic Pain in Females.

PURPOSE OF REVIEW: The purpose of this paper is to review the most recent literature on non-surgical therapeutic options for chronic pelvic pain in females. RECENT FINDINGS: Chronic pelvic pain can arise from virtually any organ system in the human body. If a precise etiology is identified, the management of chronic pelvic pain can be tailored accordingly. In some cases, patients with chronic pelvic pain can remain without a specific diagnosis. In these circumstances, adequate symptom control can still be achieved even if no underlying disorder is found. Although chronic pelvic pain is often a difficult disorder to manage, several non-surgical management options exist. Employing a multidisciplinary approach, most patients can achieve adequate symptom relief, usually without the need for surgical intervention.

Urodynamic autonomic bladder dysfunction in women with complex chronic pelvic pain is associated with small fiber polyneuropathy.

AIMS: Small fiber neuropathy/polyneuropathy (SFN) has been found to be present in 64% of complex (refractory or multisystem) chronic pelvic pain (CPP) patients. The small fiber dysfunction seen in SFN can negatively impact autonomic control of micturition in addition to pain. This study investigated the clinical association of autonomic dysfunction (detrusor underactivity and primary bladder neck obstruction [BNO]) on video urodynamics (VUDS) with SFN in patients with CPP. METHODS: This was a retrospective observational study, querying data from patients with complex CPP. Inclusion criteria were: the presence of complex (refractory or multisystem) CPP, and completion of both (1) subspecialty autonomic neurology evaluation for SFN and (2) high-quality VUDS performed according to ICS standards. Autonomic bladder dysfunction (BNO or detrusor underactivity) on VUDS was compared to the presence of SFN. RESULTS: Thirty-two female patients with complex CPP met criteria. Of the 32, 23 (72%) were found to have SFN. Patient with autonomic bladder dysfunction (BNO or detrusor underactivity) were more likely to have SFN (OR = 9.5 [95% CI: 1.641, 55.00], p = 0.007). Post-void residual volume was higher in the SFN group (p = 0.011 [95% CI: 13.12, 94.0]) and symptoms of urge urinary incontinence were more likely to be present (p = 0.000 [95% CI: -3.4, -1.25]). CONCLUSIONS: Patients with complex CPP with autonomic bladder dysfunction are more likely to have SFN. This suggests patients with complex CPP should be considered for diagnosis and treatment of SFN, particularly if BNO or detrusor underactivity is noted on VUDS evaluation.

Robotic assisted proximal dorsal urethral diverticulectomy.

INTRODUCTION AND HYPOTHESIS: Urethral diverticula are rare but clinically significant entities among female patients. Ventrally located, mid-to distal, simple or horseshoe diverticula are most commonly observed and are usually repaired via a transvaginal approach with varying levels of difficulty but high success rates. Dorsally (anteriorly) located urethral diverticula are more challenging to repair secondary to the need to access the side of the urethra opposite the vaginal lumen, abutting the external urethral sphincter. Unique proximal anatomy in the case presented led to careful consideration of the surgical options. METHODS: We present a review of techniques reported in the literature and a video demonstrating our technique for transabdominal robot-assisted laparoscopic excision of a large, dorsal, very proximally located, crescenteric urethral diverticulum in a patient who initially presented with urosepsis. RESULTS: Robotic-assisted excision of the urethral diverticulum was accomplished in 3:27 h with an estimated blood loss of 50 cc. Vaginal counter-incision was not necessary. The patient's postoperative course was uneventful. Postoperative voiding cystourethrogram prior to suprapubic catheter removal revealed a well-healed repair without extravasation. At 6-month follow-up, she denied any de novo lower urinary tract symptoms such as urinary incontinence, post-void dribbling, urinary tract infection or urinary hesitancy. CONCLUSIONS: Dorsal urethral diverticulum in women, particularly when very proximal, can present a diagnostic and surgical challenge for reconstructive pelvic surgeons. The robotic approach to urethral diverticulectomy is feasible for a proximal dorsal urethral diverticulum which lies cephalad to the pubic symphysis. This or other laparoscopic applications may also be considered as an adjunct to the standard vaginal approach for complex urethral diverticuli with a proximal dorsal component.

Neuromodulation for Chronic Pelvic Pain: A Single-Institution Experience With a Collaborative Team.

BACKGROUND: Secondary to the complex care, involved specialty providers, and various etiologies, chronic pelvic pain patients do not receive holistic care. OBJECTIVE: To compare our general and neuromodulation cohorts based on referrals, diagnosis, and therapy and describe our neuromodulation patients. METHODS: A multidisciplinary team was established at our center. The intake coordinator assessed demographics and facilitated care of enrolled patients. Outcomes were compared using minimal clinical important difference of current Numerical Rating Scale (NRS) between patients with neuropathic pain who received neuromodulation and those who did not. The neuromodulation cohort completed outcome metrics at baseline and recent follow-up, including NRS score (best, worst, and current), Oswestry Disability Index (ODI), Beck Depression Inventory, and Pain Catastrophizing Scale. RESULTS: Over 7 yr, 233 patients were referred to our consortium and 153 were enrolled. A total of 55 patients had neuropathic pain and 44 of those were managed medically. Eleven underwent neuromodulation. A total of 45.5% patients of the neuromodulation cohort were classified as responders by minimal clinically important difference compared to 26.6% responders in the control cohort at most recent follow-up (median 25 and 33 mo, respectively). Outcome measures revealed improvement in NRS at worst (P = .007) and best (P = .025), ODI (P = .014), and Pain Catastrophizing Scale Rumination (P = .043). CONCLUSION: Eleven percent of patients were offered neuromodulation. There were more responders in the neuromodulation cohort than the conservatively managed neuropathic pain cohort. Neuromodulation patients showed significant improvement at 29 mo in NRS best and worst pain, disability, and rumination. We share our algorithm for patient management.

Pentosan Polysulfate Maculopathy: What Urologists Should Know in 2020.

OBJECTIVE: To conduct a review of current literature to assess whether an association exists between Pentosan Polysulfate Sodium and the development of macular disease, as it is the only oral medication approved by the Food and Drug Administration for the management of interstitial cystitis. MATERIALS AND METHODS: A systematic review was conducted by the authors separately, with review methods established prior to the conduct of the review. Databases searched included PubMed, Ovid, Medline, EBSCO, and Google Scholar. A search was conducted for the terms "Pentosan Polysulfate Maculopathy," "Pentosan Polysulfate Retinopathy," and "Interstitial Cystitis Maculopathy." All papers reporting on primary data were included. There were no study sponsors. RESULTS: A total of 14 papers reporting on primary data were identified. Most papers reported on the development of macular disease in the setting of chronic pentosan polysulfate sodium exposure. No randomized controlled trials have been performed to date and data was insufficient to perform a meta-analysis. Nevertheless, patients with interstitial cystitis were more likely to receive a diagnosis of maculopathy after several years of the medication use. CONCLUSION: Although the nature of the published studies renders them prone to confounders, currently available data suggest an increased risk for developing maculopathy after years of pentosan polysulfate sodium use. In light of this, and the marginal effectiveness of the medication for the average individual, we suggest that education be provided as to the possible association and that regular ophthalmic evaluation be recommended for patients who are continued on chronic Pentosan Polysulfate Sodium.

Chronic Pelvic Pain Patients Demonstrate Higher Catastrophizing in Association with Pelvic Symptoms and Comorbid Pain Diagnoses.

OBJECTIVE: To elucidate the relationship between catastrophization and pelvic pain symptomatology in chronic pelvic pain (CPP) patients using standardized questionnaires. METHODS: CPP patients completed standardized questionnaires which included: genitourinary pain index, patient health questionnaire for anxiety and depression, interstitial cystitis symptom index, and pelvic floor distress inventory. Scores and number of comorbidities were compared to Pain Catastrophizing Scale (PCS) by linear regression. Patients categorized as "extreme catastrophizing" (PCS score ≥30), traditionally associated with worse outcomes in the pain literature [10-11], were also analyzed separately. RESULTS: 184 patients were included (mean age 42 years, N = 23 male). Higher number of pain comorbidities was correlated to PCS (P < .001) as well as higher scores on all standardized questionnaires (P < .001). Forty-four percent of patients (81/184) were extreme catastrophizers and scored significantly worse on all standardized measures when compared to nonextreme catastrophizers. Mean scores for nonextreme vs extreme catastrophizers were: genitourinary pain index (25.7 ± 6.8 vs 32.7 ± 6.5, P < .001), interstitial cystitis symptom index (6.5 ± 4.7 vs 9.4 ± 5.8, P < .001), pelvic floor distress inventory (88.8 ± 52 vs 121.1 ± 62.8, P < .001), patient health questionnaire anxiety (1.7 ± 2.0 vs 3.6 ± 2.1, P < .001), and depression (1.4 ± 1.6 vs 3.3 ± 2.0, P < .001). Number of comorbidities was not significant predictor of extreme catastrophizing (3.5 vs 3.7 P = .22). CONCLUSION: Higher scores on standardized questionnaires and more comorbidities was associated with more catastrophizing in CPP patients. This study highlights the significance of standardized questionnaires, including the PCS, to predict which patients may be extreme catastrophizers and thus subject to worse outcomes. Future studies are needed to look at catastrophization as a potentially modifiable and treatable risk factor.

Estrogen replacement is protective to the effect of in vitro hypoxia on female rabbit bladder and pelvic floor contractile response.

Purpose: To explore the effect of estrogen replacement on pelvic floor and bladder contractile response to electrical field stimulation, following in vitro hypoxia in an animal model of surgical menopause. Materials and Methods: Twelve female adult rabbits were divided into three groups: control, ovariectomy, and ovariectomy with estradiol replacement. At 4 weeks animals were euthanized. Bladder, coccygeus, and pubococcygeus were isolated. Tissues were equilibrated with oxygenated Tyrodes containing glucose and stimulated with electrical field stimulation. Tissues were then stimulated under hypoxic conditions for 1 hour using nitrogenated Tyrodes without glucose. Tissues were then re-oxygenated for 2 hours and stimulated. Results: Pelvic floor required 10 times the stimulation duration (power) to achieve maximum contraction at 2 g baseline tension (10 ms duration) when compared to bladder (1 ms duration). Maximal tension generated was significantly greater for bladder than pelvic floor. Coccygeus and pubococcygeus were significantly less sensitive to the effects of hypoxia and had stable contractile response to field stimulation throughout the hour of hypoxia. Hypoxia resulted in progressive and rapid decline of bladder contractile strength. Following hypoxia, pelvic floor contractile recovery was superior to bladder. Improvement in the contractile response of both bladder and pelvic floor, during the period of post-hypoxia re-oxygenation, was significantly greater in ovariectomy animals treated with estradiol replacement. Conclusions: Replacement of estradiol at time of ovariectomy reduced oxidative stress on tissue and was protective to the effects of hypoxia on pelvic floor and bladder contractile function.

Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra.

AIMS: We sought to determine whether somatic lumbar nerve transfer to the pelvic nerve's anterior vesical branch after sacral decentralization for detrusor muscle reinnervation also leads to aberrant innervation of the bladder outlet. METHODS: Twenty-six female mongrel hound dogs underwent transection of sacral dorsal and ventral spinal roots (ie, sacral decentralization). Immediately afterward, 12 received genitofemoral nerve transfer and 9 received femoral nerve branch transfer. Five were left sacrally decentralized. Controls included 3 sham-operated and 6 unoperated. Eight months postsurgery, the bladder and urethra were injected with retrograde tracing dyes cystoscopically. After 3 weeks, detrusor and urethral pressures were assayed electrophysiologically immediately before euthanasia and characterization of neural reinnervation. RESULTS: Electrical stimulation of spinal cords or roots did not lead to increased urethral sphincter pressure in nerve transfer animals, compared with decentralized animals, confirming a lack of functional reinnervation of the bladder outlet. In contrast, mean detrusor pressure increased after lumbar cord/root stimulation. In sham/unoperated animals, urethral and bladder dye injections resulted in labeled neurons in sacral level neural structures (dorsal root ganglia [DRG], sympathetic trunk ganglia [STG], and spinal cord ventral horns); labeling absent in decentralized animals. Urethral dye injections did not result in labeling in lumbar or sacral level neural structures in either nerve transfer group while bladder dye injections lead to increased labeled neurons in lumbar level DRG, STG, and ventral horns, compared to sacrally decentralized animals. CONCLUSION: Pelvic nerve transfer for bladder reinnervation does not impact urethral sphincter innervation.

Spontaneous voiding is surprisingly recoverable via outlet procedure in men with underactive bladder and documented detrusor underactivity on urodynamics.

AIMS: To identify clinical and urodynamic factors leading to spontaneous voiding in men with detrusor underactivity (DU) and suspected bladder outlet obstruction who underwent an outlet de-obstruction procedure. METHODS: We identified 614 men who underwent an outlet procedure at our institution from 2005 to 2014. Men were stratified by bladder contractility index (BCI). The primary outcome was spontaneous voiding after surgery. Data were analyzed in Statistical analysis system software. RESULTS: Of the 131 men who underwent preoperative urodynamics, 122 (mean age 68 years) had tracings available for review. DU (BCI < 100) was identified in 54% (66 of 122), of whom only 68% (45 of 66) voided spontaneously before surgery, compared with 82% (46 of 56) of men with BCI ≥ 100. At a mean follow-up of 6.4 months postoperatively, 79% (52 of 66) of men with DU were able to void spontaneously, compared with 96% (54 of 56) of men with BCI ≥ 100. In men with a BCI < 100 unable to void before surgery, 57% (12 of 21) recovered spontaneous voiding after surgery. On logistic regression for the outcome postoperative spontaneous voiding, significant preoperative characteristics, and urodynamic factors included preoperative spontaneous voiding (odds ratio [OR] = 9.460; 95% confidence interval [CI] = 2.955-30.289), increased maximum flow rate (Qmax; OR = 1.184; 95% CI = 1.014-1.382), increased detrusor pressure at maximum flow (Pdet@Qmax; OR = 1.032; 95% CI = 1.012-1.052), DU with BCI < 100 (OR = 0.138; 95% CI = 0.030-0.635), and obstruction with bladder outlet obstruction index > 40 (OR = 5.595; 95% CI = 1.685-18.575). CONCLUSION: Outlet de-obstruction improves spontaneous voiding in men with DU and may benefit men who do not meet the urodynamic threshold for obstruction.

Can magnetic resonance imaging differentiate among transurethral bulking agent, urethral diverticulum, and periurethral cyst?

PURPOSE: To evaluate magnetic resonance imaging findings that differentiate among periurethral bulking agents (primarily collagen), urethral diverticulum, and periurethral cyst. METHODS: We searched our radiologic database retrospectively from 2001 to 2017 for periurethral cystic lesions, identifying a total of 50 patients with 68 lesions. Final diagnoses in 68 lesions were bulking agents (27), urethral diverticula (29), and periurethral cysts (12). Two abdominal radiologists, blinded to clinical history, independently evaluated T1, T2, and post-contrast images. The readers assessed number, morphological features, location, connection to urethra and mass effect, signal intensity, and enhancement for each lesion. Fisher exact test and logistic regression analysis were performed for each univariate significant feature. The operative and pathologic reports were the reference standard. RESULTS: Magnetic resonance imaging features found more often in bulking agents versus urethral diverticulum were multiple lesions (P = 0.011), upper or upper-mid-urethral location (P ≤ 0.0001), lack of internal fluid/fluid level (P = 0.002), no urethral connection (P = 0.005), T1 isointensity, and T2 mild hyperintensity compared to muscles but lower T2 signal than urine (P < 0.0001). Most cases of urethral diverticula and periurethral cysts were detected at mid- and lower urethra. Urethral diverticula were larger than bulking agents and periurethral cysts (P = 0.005 and P = 0.023) (mean diameter = 24, 16, 15 mm, respectively). Most bulking agents (93%) and urethral diverticula (90%) showed mass effect on urethra, while periurethral cysts (75%) did not (P < 0.0001). CONCLUSION: Signal intensity and lesion characterization on magnetic resonance imaging can significantly differentiate bulking agent from urethral diverticulum and periurethral cyst. Radiologists should consider differential diagnosis of a bulking agent, especially when distinguishing characteristics described here are present to prevent incorrect diagnosis and ultimately unnecessary surgical intervention.

Surgery for female SUI: The ICI algorithm.

INTRODUCTION: Stress urinary incontinence (SUI) is common in women and can significantly impact quality of life. METHODS: This is a review of the 6th International Consultation on Incontinence (ICI) chapter analyzing level of evidence on surgical treatment of SUI as well as the consensus algorithm that resulted from the detailed work in the committee report as of April 2017. Included studies in this review were selected to highlight the algorithm for management. RESULTS: Non-operative and surgical treatment options exist; conservative therapies comprise first line management, but if SUI remains bothersome, surgical treatment should be considered. Bulking agents offer a minimally invasive option with moderate short-term success rates. The most commonly performed surgical treatments for SUI are mid-urethral and pubovaginal slings, with high cure rates and patient satisfaction. Retropubic suspension is a more traditional but widely accepted procedure. Single incision sling, adjustable sling, or artificial urinary sphincter may be appropriate in carefully selected patients. CONCLUSIONS: The choice of surgical procedure should be made only after a thorough discussion and shared decision between the patient and surgeon regarding risks, benefits, and alternatives. A trial of conservative therapy should be conducted where relevant. Referral to a specialist should be considered in women with a more complex presentation.

The Clinical Role of LASER for Vulvar and Vaginal Treatments in Gynecology and Female Urology: An ICS/ISSVD Best Practice Consensus Document.

In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review. Most of the available studies are limited by their design; for example, they lack a control group, patients are not randomized, follow-up is short term, series are small, LASER is not compared with standard treatments, and most studies are industry sponsored. Because of these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration after LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women. The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, although short-term complications seem to be uncommon, data concerning long-term outcomes are lacking. Therefore, at this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit.

The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology: An ICS/ISSVD best practice consensus document.

BACKGROUND: The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology is controversial. AIMS: In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review. MATERIALS & METHODS: This project was developed between January and September 2018. The development of this document followed the ICS White Paper Standard Operating Procedures. RESULTS: Most of the available studies are limited by their design; for example they lack a control group, patients are not randomized, follow up is short term, series are small, LASER is not compared with standard treatments, and studies are industry sponsored. Due to these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration following LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women. DISCUSSION: The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, while short-term complications seem to be uncommon, data concerning long-term outcomes are lacking. CONCLUSION: At this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit.