Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

Characteristics of systemic testosterone therapy for female hypoactive sexual desire disorder-a claims database analysis.

BACKGROUND: Testosterone therapy (TTh) is recommended for postmenopausal women with hypoactive sexual desire disorder (HSDD); however, there remain insufficient data to support use of TTh in premenopausal women with sexual dysfunction. AIM: In this study, we used a large national database to evaluate prescribing trends of TTh for women with HSDD. METHODS: We conducted a cohort analysis of information from electronic health records acquired from the data network TriNetX Diamond. The study cohort consisted of women 18-70 years of age with a diagnosis of HSDD. We analyzed trends of testosterone prescriptions, routes of testosterone administration, and coadministration of testosterone with estrogen. OUTCOMES: Despite an increase in rates of testosterone prescriptions for HSDD, there remains a high degree of variability in the duration of treatment, route of administration, and coadministration of estrogen with significant underprescription of testosterone. RESULTS: Our query of the TriNetX database led to the identification of 33 418 women diagnosed with HSDD at a mean age of 44.2 ± 10.8 years, among whom 850 (2.54%) women received a testosterone prescription. The testosterone prescriptions were highly variable with regard to duration and route of administration and coadministration with estrogen. For all patients until 2015, the prevalence of testosterone prescriptions for HSDD showed a positive quadratic relation was observed. Since 2015 a linear increase in prevalence was observed, with the highest rate of increase for patients aged 41-55 years. CLINICAL IMPLICATIONS: The findings of this study reveal a significant need for further research investigating the optimal use of TTh to enhance the sexual health of women with HSDD, and further studies on the long-term effects of testosterone use must be undertaken to ensure that patients have access to safe and effective treatment. STRENGTHS AND LIMITATIONS: Limitations to this study include patient de-identification and lack of availability of testosterone dosage data. However, this study also has many strengths, including being the first, to our knowledge, to characterize the prescribing trends of testosterone for women with HSDD. CONCLUSION: Testosterone therapy should be considered as a potential therapy for premenopausal female patients with HSDD. Further studies on the long-term effects of testosterone use must be undertaken to address disparities in the management of HSDD and to ensure patients can access treatment.

Lumbar endoscopic spine surgery for persistent genital arousal disorder/genitopelvic dysesthesia resulting from lumbosacral annular tear-induced sacral radiculopathy.

BACKGROUND: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by distressing, abnormal genitopelvic sensations, especially unwanted arousal. In a subgroup of patients with PGAD/GPD, cauda equina Tarlov cyst-induced sacral radiculopathy has been reported to trigger the disorder. In our evaluation of lumbosacral magnetic resonance images in patients with PGAD/GPD and suspected sacral radiculopathy, some had no Tarlov cysts but showed lumbosacral disc annular tear pathology. AIM: The aims were 2-fold: (1) to utilize a novel multidisciplinary step-care management algorithm designed to identify a subgroup of patients with PGAD/GPD and lumbosacral annular tear-induced sacral radiculopathy who could benefit from lumbar endoscopic spine surgery (LESS) and (2) to evaluate long-term safety and efficacy of LESS. METHODS: Clinical data were collected on patients with PGAD/GPD who underwent LESS between 2016 and 2020 with at least 1-year follow-up. LESS was indicated because all had lumbosacral annular tear-induced sacral radiculopathy confirmed by our multidisciplinary management algorithm that included the following: step A, a detailed psychosocial and medical history; step B, noninvasive assessments for sacral radiculopathy; step C, targeted diagnostic transforaminal epidural spinal injections resulting in a temporary, clinically significant reduction of PGAD/GPD symptoms; and step D, surgical intervention with LESS and postoperative follow-up. OUTCOMES: Treatment outcome was based on the validated Patient Global Impression of Improvement, measured at postoperative intervals. RESULTS: Our cohort included 15 cisgendered women and 5 cisgendered men (mean ± SD age, 40.3 ± 16.8 years) with PGAD/GPD who fulfilled the criteria of lumbosacral annular tear-induced sacral radiculopathy based on our multidisciplinary management algorithm. Patients were followed for an average of 20 months (range, 12-37) post-LESS. Lumbosacral annular tear pathology was identified at multiple levels, the most common being L4-L5 and L5-S1. Twenty-two LESS procedures were performed in 20 patients. Overall, 80% (16/20) reported improvement on the Patient Global Impression of Improvement; 65% (13/20) reported improvement as much better or very much better. All patients were discharged the same day. There were no surgical complications. CLINICAL IMPLICATIONS: Among the many recognized triggers for PGAD/GPD, this subgroup exhibited lumbosacral annular tear-induced sacral radiculopathy and experienced long-term alleviation of symptoms by LESS. STRENGTHS AND LIMITATIONS: Strengths include long-term post-surgical follow-up and demonstration that LESS effectively treats patients with PGAD/GPD who have lumbosacral annular tear-induced sacral radiculopathy, as established by a multidisciplinary step-care management algorithm. Limitations include the small study cohort and the unavailability of a clinical measure specific for PGAD/GPD. CONCLUSION: LESS is safe and effective in treating patients with PGAD/GPD who are diagnosed with lumbosacral annular tear-induced sacral radiculopathy.

Who is at the Podium? Women Urologist Speakers at Recent AUA Meetings.

OBJECTIVE: To quantify the representation of women urologists as invited speakers at the AUA Annual Meeting. METHODS: Programs for the AUA Annual Meeting were reviewed from 2017 to 2019. Topics of sessions and genders of moderators and panelists were collected. Percentages of women urologists as well as topics of sessions were compared between years. RESULTS: Women urologists comprised 60 of 467 moderators (12.8%) and 63 of 614 panelists (10.3%). Sessions about infection had the most women urologist moderators while oncology had the least. Sessions about FPMRS has the most women urologists as panelists. Male urologists were more likely to be full professors compared to women urologists. While the percentage of female panelists fluctuated, the percentage of female moderators decreased each year. CONCLUSION: Although the proportion of women to men in urology is increasing, the number and proportion of woman urologist panelists and moderators at the annual AUA meeting does not reflect this trend. It is important to recognize and correct this discrepancy, as well as to increase visibility of women and others underrepresented in the field.

Poor prognosis of bladder cancer patients with occult lymph node metastases treated with neoadjuvant chemotherapy.

OBJECTIVES: To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre-treated patients found to be lymph node (LN)-positive at the time of radical cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: Of 1484 patients treated with RC/PLND for UCB from 2000 to 2010, we analysed 198 patients with clinically non-metastatic (cN0M0) muscle-invasive UCB who were found to be LN-positive at RC/PLND. As patients not receiving perioperative chemotherapy were significantly older and comorbid, we compared LN-positive patients previously treated with NAC (32 patients) to LN-positive patients treated with adjuvant chemotherapy (AC, 49 patients) using Cox proportional hazards models. A sensitivity analysis was designed to account for the additional time to RC in NAC patients. RESULTS: The 3-year recurrence-free survival estimate for LN-positive NAC patients was 26%, compared with 60% for LN-positive AC patients. LN-positive patients treated with NAC had significantly higher risks of disease recurrence and cancer-specific mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.58-5.19, P = 0.001 and HR 2.50, 95% CI 1.34-4.65, P = 0.004, respectively) and multivariable analyses adjusting for pathological stage and LN density (HR 3.11, 95% CI 1.59-6.07, P = 0.001 and HR 3.05, 95% CI 1.46-6.35, P = 0.003, respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC pre-treated LN-positive patients. CONCLUSION: LN-positive patients previously treated with NAC have a poor prognosis, significantly worse than LN-positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials.

Impact of Ureteroscopy Before Nephroureterectomy for Upper Tract Urothelial Carcinoma on Oncologic Outcomes.

OBJECTIVE: To compare the oncologic outcomes of patients with upper tract urothelial carcinoma undergoing nephroureterectomy (NU) with and without prior ureteroscopy (URS). METHODS: We reviewed records of all patients with no prior history of bladder cancer who underwent NU at our institution (n = 201). We compared patients who underwent URS before NU with patients who proceeded directly to NU based on imaging alone. After excluding patients undergoing URS with therapeutic intent, we used multivariable Cox proportional hazards models, adjusting for tumor characteristics with cancer-specific survival (CSS), intravesical recurrence-free survival, metastasis-free survival (MFS), and overall survival (OS) as end points. This study received institutional review board approval. RESULTS: A total of 144 (72%) patients underwent URS before NU, and 57 (28%) patients proceeded directly to NU. The median follow-up time for survivors was 5.4 years from diagnosis. The performance of diagnostic URS before NU was significantly associated with IR (hazard ratio 2.58; 95% CI 1.47, 4.54; P = .001), although it was not associated with CSS, MFS, or OS. The adjusted intravesical recurrence-free survival probability 3 years after diagnosis is 71% and 42% for patients who did not and did receive URS before NU, respectively (adjusted risk difference 30%; 95% CI 13%, 47%). CONCLUSION: We did not find evidence that URS adversely impacts disease progression and survival in patients with upper tract urothelial carcinoma. Although patients are at higher risk for IR after NU when they have undergone prior diagnostic URS, their CSS, MFS, and OS are not significantly affected.

Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder.

UNLABELLED: Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p=0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p=0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p=0.005) and lymph node-positive disease (77% vs 56%, p=0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-altered tumors experienced worse RFS (HR: 5.76; p<0.001) and worse CSS (HR: 2.94; p=0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. PATIENT SUMMARY: Using next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches.

Risk factors for the development of parastomal hernia after radical cystectomy.

PURPOSE: Parastomal hernia is a frequent complication of stoma formation after radical cystectomy. We determined the prevalence and risk factors for the development of parastomal hernia after radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective study of 433 consecutive patients who underwent open radical cystectomy and ileal conduit between 2006 and 2010. Postoperative cross-sectional imaging studies performed for routine oncologic followup (1,736) were evaluated for parastomal hernia, defined as radiographic evidence of protrusion of abdominal contents through the abdominal wall defect created by forming the stoma. Univariable and multivariable Cox regression analyses were used to determine clinical and surgical factors associated with parastomal hernia. RESULTS: Complete data were available for 386 patients with radiographic parastomal hernia occurring in 136. The risk of a parastomal hernia developing was 27% (95% CI 22, 33) and 48% (95% CI 42, 55) at 1 and 2 years, respectively. Clinical diagnosis of parastomal hernia was documented in 93 patients and 37 were symptomatic. Of 16 patients with clinical parastomal hernia referred for repair 8 had surgery. On multivariable analysis female gender (HR 2.25; 95% CI 1.58, 3.21; p<0.0001), higher body mass index (HR 1.08 per unit increase; 95% CI 1.05, 1.12; p<0.0001) and lower preoperative albumin (HR 0.43 per gm/dl; 95% CI 0.25, 0.75; p=0.003) were significantly associated with parastomal hernia. CONCLUSIONS: The overall risk of radiographic evidence of parastomal hernia approached 50% at 2 years. Female gender, higher body mass index and lower preoperative albumin were most associated with the development of parastomal hernia. Identifying those at greatest risk may allow for prospective surgical maneuvers at the time of initial surgery, such as placement of prophylactic mesh in selected patients, to prevent the occurrence of parastomal hernia.