Impact of sacrocolpopexy for the management of pelvic organ prolapse on voiding dysfunction and uroflowmetry parameters: a prospective cohort study.

PURPOSE: Voiding difficulties in the context of pelvic organ prolapse are often neglected or underestimated. To date, there are heterogeneous data available on the outcome of a surgical correction of pelvic organ prolapse and the impact on concomitant voiding dysfunction. The primary aim of this study was to evaluate whether laparoscopic sacrocolpopexy would resolve preoperative voiding dysfunction and the impact on objective uroflowmetry parameters. METHODS: Data from 103 women undergoing sacrocolpopexy for prolapse stage ≥ II with concurrent objective and/or subjective voiding dysfunction were prospectively evaluated. All women underwent full urogynecological examination, and completed a validated questionnaire pre- and postoperatively. Objective uroflowmetry parameters and subjective outcome data regarding voiding functions were compared pre- and postoperatively. RESULTS: All points of the POP-Q system improved significantly pre- to postoperatively (p < 0.001). Preoperatively, 42 of 103 women showed a postvoid residual ≥ 100 ml, whereas only six women had a relevant postvoid residual postoperatively. In total, the postoperative postvoid residual in all women decreased significantly (p < 0.001). Voiding time decreased significantly postoperatively (p < 0.001) with no significant change in the voided volume (p = 0.352). The maximum flow rate increased postoperatively, reaching no statistically significant change (p = 0.132). Subjective outcome measurements (weak or prolonged stream, incomplete bladder emptying, and straining to void) improved significantly (p < 0.001 for all the questions). CONCLUSION: Our prospective study demonstrates that sacrocolpopexy to correct pelvic organ prolapse can successfully resolve voiding dysfunction, as both objective and subjective parameters improved significantly after surgery.

Should Groin Recurrence Still Be Considered as a Palliative Situation in Vulvar Cancer Patients?: A Brief Report.

OBJECTIVE: To assess survival after groin recurrence in patients with vulvar cancer in the transition period of the implementation of the sentinel lymph node biopsy procedure. Recurrence of groin metastases in vulvar cancer patients is assumed to be lethal. It is unknown if early detection of relapse and multimodal treatment strategies improve the outcome of patients with groin recurrence. METHODS: Multicenter retrospective cohort study of patients with recurrent vulvar cancer who presented with groin and/or pelvic lymph node metastases between 2000 and 2014 at 3 tertiary referral hospitals. Our primary outcome was to assess survival after groin recurrence of vulvar cancer and the influence of multimodal treatment. All analyses were done using Stata 12 (Stata Corporation, College Station, Tex). Hazard ratios (HRs) and their corresponding 95% confidence intervals were calculated using a Cox proportional hazards model. RESULTS: We identified 30 patients with a median time from diagnosis to groin recurrence of 10 months. The median follow-up of patients who were alive at the time of analysis was 22 months (range, 9-123 months). A Kaplan-Meier estimate showed an overall survival rate of 50% after 7 years. Patients with multimodal groin relapse treatment performed better than those with single-mode treatment (HR, 0.25; P = 0.037). Lymph node metastases at diagnosis were also associated with lower survival (HR, 6.11; P = 0.020). We observed a trend toward lower survival with a tumor size greater than T1 (HR, 2.55; P = 0.111). The time from diagnosis to groin recurrence had no influence on survival (HR, 0.99; P = 0.561). CONCLUSIONS: Close follow-up visits for at least 2 years are important to detect recurrent disease in groin and pelvic lymph nodes. Treatment of recurrent groin metastases should no longer be considered as a palliative situation--given that one half of the patients will have long-term survival after multimodal treatment strategies.

Recurrent Pelvic Organ Prolapse after Sacrocolpopexy-A Surgical Challenge.

Background: Repeat sacrocolpopexy (reSCP) for recurrent pelvic organ prolapse (POP) is a rare and complex condition with little understanding of how to manage. Most authors recommend complete reSCP regardless of the underlying cause of the failure. This retrospective cohort study presents our management workflow and how to systematically approach this challenging situation. Methods: From 2017 to 2021, we analyzed all women undergoing surgery for recurrent POP after sacrocolpopexy at our tertiary referral hospital at the department of urogynecology. Preoperatively, all women underwent a structured work-up consisting of answering the validated German female pelvic floor questionnaires, a clinical examination utilizing the POP-Q staging system according to the International Continence Society (ICS), and a pelvic floor ultrasound. The surgical management was based on the preoperative findings and was adapted individually during surgery if indicated according to the estimated underlying problem for recurrence. Results: In total, 377 women underwent a primary laparoscopic sacrocolpopexy. However, ten women presented with a symptomatic recurrent prolapse requiring further surgical intervention. A reSCP was performed in eight women, including two with additional laparoscopic paravaginal repair to correct the displaced mesh placement at initial surgery. A vaginal correction was indicated in two women with an isolated posterior compartment prolapse. The analysis demonstrates that reSCP has a low intraoperative complication rate and high subjective and objective success rates. Conclusions: We could demonstrate that individualized reSCP after initial SCP is a challenging yet feasible and safe treatment option, but there may be suitable alternatives. If women undergo pre- and intraoperative standardized problem-oriented examinations, we can often identify the cause of the recurrent prolapse. Tailored surgery must be subsequently performed.

Gender-specific prolactin thresholds to determine prolactinoma size: a novel Bayesian approach and its clinical utility.

Background: In clinical practice, the size of adenomas is crucial for guiding prolactinoma patients towards the most suitable initial treatment. Consequently, establishing guidelines for serum prolactin level thresholds to assess prolactinoma size is essential. However, the potential impact of gender differences in prolactin levels on estimating adenoma size (micro- vs. macroadenoma) is not yet fully comprehended. Objective: To introduce a novel statistical method for deriving gender-specific prolactin thresholds to discriminate between micro- and macroadenomas and to assess their clinical utility. Methods: We present a novel, multilevel Bayesian logistic regression approach to compute observationally constrained gender-specific prolactin thresholds in a large cohort of prolactinoma patients (N = 133) with respect to dichotomized adenoma size. The robustness of the approach is examined with an ensemble machine learning approach (a so-called super learner), where the observed differences in prolactin and adenoma size between female and male patients are preserved and the initial sample size is artificially increased tenfold. Results: The framework results in a global prolactin threshold of 239.4 µg/L (95% credible interval: 44.0-451.2 µg/L) to discriminate between micro- and macroadenomas. We find evidence of gender-specific prolactin thresholds of 211.6 µg/L (95% credible interval: 29.0-426.2 µg/L) for women and 1,046.1 µg/L (95% credible interval: 582.2-2,325.9 µg/L) for men. Global (that is, gender-independent) thresholds result in a high sensitivity (0.97) and low specificity (0.57) when evaluated among men as most prolactin values are above the global threshold. Applying male-specific thresholds results in a slightly different scenario, with a high specificity (0.99) and moderate sensitivity (0.74). The male-dependent prolactin threshold shows large uncertainty and features some dependency on the choice of priors, in particular for small sample sizes. The augmented datasets demonstrate that future, larger cohorts are likely able to reduce the uncertainty range of the prolactin thresholds. Conclusions: The proposed framework represents a significant advancement in patient-centered care for treating prolactinoma patients by introducing gender-specific thresholds. These thresholds enable tailored treatment strategies by distinguishing between micro- and macroadenomas based on gender. Specifically, in men, a negative diagnosis using a universal prolactin threshold can effectively rule out a macroadenoma, while a positive diagnosis using a male-specific prolactin threshold can indicate its presence. However, the clinical utility of a female-specific prolactin threshold in our cohort is limited. This framework can be easily adapted to various biomedical settings with two subgroups having imbalanced average biomarkers and outcomes of interest. Using machine learning techniques to expand the dataset while preserving significant observed imbalances presents a valuable method for assessing the reliability of gender-specific threshold estimates. However, external cohorts are necessary to thoroughly validate our thresholds.

Impact of Defined Risk Factors on Degree of Urinary Stress Incontinence and Sling Outcome: A Retrospective Cohort Analysis.

Urinary stress incontinence is a distressing condition that has a severe impact on quality of life for most affected women. The insertion of the suburethral tension-free vaginal tape (TVT) is regarded as the gold-standard surgical treatment option. It is unclear whether all women with severe SUI benefit equally from TVT. Thus, the aim of our study was to identify risk factors for severe SUI and determine whether successful the resolution of incontinence after a TVT procedure was different in women with a higher degree of SUI. In total, 168 women were included in this retrospective cohort study. Women with severe SUI showed a significantly lower maximum urethral closure pressure (MUCP) (median 53 cmH2O in moderate vs. 39 cmH2O in severe, p = 0.001) and higher BMI (median 26.1 kg/m2 in moderate vs. 28.5 kg/m2 in severe, p = 0.045). Sonographic bladder neck funneling was detected significantly more often in women with severe SUI (27% in moderate vs. 57% in severe, p = 0.004). Lower MUCP and higher BMI were identified as significant predictors of severe SUI (p < 0.032). There was no difference in parity, age, functional urethral length and negative urethral stress pressure. Overall postoperative continence after the insertion of TVT was 91.9%. We found no significant difference in postoperative continence between women with severe vs. moderate SUI, suggesting that in our cohort the success of TVT was not significantly affected by the severity of SUI. In our cohort, low MUCP and high BMI were shown to be significant predictors of SUI severity. Nevertheless, treatment success of SUI with TVT did not differ substantially in women with more severe SUI.

Percutaneous Tibial Nerve Stimulation in the Treatment of Refractory Idiopathic Overactive Bladder Syndrome: A Retrospective Cohort Study.

BACKGROUND: Overactive bladder (OAB) is a syndrome defined as urinary urgency, accompanied by increased frequency and nocturia with or without urge incontinence, in the absence of urinary tract infection or other obvious pathology. The standard therapies are anticholinergic agents, selective beta-3 adrenoreceptor agonists, or intradetrusor injections of botulinum toxin (BTX-A). For patients with contraindications for BTX-A or drug therapies, percutaneous tibial nerve stimulation (PTNS) may be used. PTNS shows fewer side effects than anticholinergic drugs and costs less than BTX-A. The primary outcome of this study was to assess the efficacy of PTNS in women with refractory OAB. METHODS: Women with refractory OAB undergoing PTNS at our tertiary referral center from 2017 to 2019 were included. The validated German Female Pelvic Floor Questionnaire and a micturition protocol were filled out before and after PTNS. PTNS was applied weekly for 12 weeks. RESULTS: Improvements in OAB symptoms were seen in daily micturition frequency, urgency, and urgency incontinence from pre- to post-PTNS (p < 0.006). Impairments to quality of daily life were significantly (p < 0.0002) less severe after PTNS. There was a significant reduction in daytime voiding frequency from a median of nine to five (p < 0.0001). CONCLUSIONS: Substantial reductions in OAB symptoms, daily micturition frequency, urgency, and urgency incontinence were found in patients with refractory OAB after PTNS.

Prolactinomas in adolescent and elderly patients-A comparative long-term analysis.

Objectives: Prolactinomas represent the most common type of secreting pituitary adenomas, yet are rarely encountered in adolescent-onset (AO; i.e. <18 years) or elderly-onset (EO; i.e. ≥65 years) cohorts. As a result, it is not clear whether long-term strategies should be focused differently at both age extremes when comparing their therapeutic outcomes. We aimed at investigating long-term endocrinological outcomes, looking for differences between the two cohorts and evaluating the dependence on continued dopamine agonist (DA) therapy. Methods: Retrospective cross-sectional comparative study analyzing prolactinoma patients with a follow-up of ≥4 years. Clinical, radiological and biochemical characteristics were assessed at diagnosis and last follow-up. Longitudinal endocrinological outcomes between groups of extreme ages (i.e. AO and EO) and middle age (i.e. ≥18 years to 65 years) were compared. Independent risk factors for long-term dependence on DAs were calculated. Results: Follow-up at ≥4 years was recorded for 108 prolactinoma patients; 10 patients with AO and 10 patients with EO. Compared to AO patients, EO patients were predominantly men (p = 0.003), and presented with significantly higher prolactin (PRL) levels (p = 0.05) and higher body mass index (p = 0.03). We noted a significant positive correlation between patients' PRL values and their age (r = 0.5, p = 0.03) or BMI (r = 0.6, p = 0.03). After a median follow-up of 115 months, remission was noted in 87 (83%) patients; 9 (90%) in AO patients, and 7 (70%) in EO patients (p = 0.58). Continuation of DAs was required in 4 patients (40%) with AO and 7 patients (70%) with EO (p = 0.37). Patients with elderly-onset were an independent predictor of long-term dependence on DAs (HR 2.8, 95% CI 1.1-7.2, p = 0.03). Conclusions: Long-term control of hyperprolactinemia and hypogonadism does not differ between members of the AO and EO cohorts, and can be attained by the majority of patients. However, adjuvant DAs are often required, independent of the age of onset. Considering the clinical significance of persistent DA therapy for the control of hyperprolactinemia in many patients at both extremes of age, long-term monitoring may become recommended, in particular in patients with elderly-onset.

Machine Learning for Outcome Prediction in First-Line Surgery of Prolactinomas.

BACKGROUND: First-line surgery for prolactinomas has gained increasing acceptance, but the indication still remains controversial. Thus, accurate prediction of unfavorable outcomes after upfront surgery in prolactinoma patients is critical for the triage of therapy and for interdisciplinary decision-making. OBJECTIVE: To evaluate whether contemporary machine learning (ML) methods can facilitate this crucial prediction task in a large cohort of prolactinoma patients with first-line surgery, we investigated the performance of various classes of supervised classification algorithms. The primary endpoint was ML-applied risk prediction of long-term dopamine agonist (DA) dependency. The secondary outcome was the prediction of the early and long-term control of hyperprolactinemia. METHODS: By jointly examining two independent performance metrics - the area under the receiver operating characteristic (AUROC) and the Matthews correlation coefficient (MCC) - in combination with a stacked super learner, we present a novel perspective on how to assess and compare the discrimination capacity of a set of binary classifiers. RESULTS: We demonstrate that for upfront surgery in prolactinoma patients there are not a one-algorithm-fits-all solution in outcome prediction: different algorithms perform best for different time points and different outcomes parameters. In addition, ML classifiers outperform logistic regression in both performance metrics in our cohort when predicting the primary outcome at long-term follow-up and secondary outcome at early follow-up, thus provide an added benefit in risk prediction modeling. In such a setting, the stacking framework of combining the predictions of individual base learners in a so-called super learner offers great potential: the super learner exhibits very good prediction skill for the primary outcome (AUROC: mean 0.9, 95% CI: 0.92 - 1.00; MCC: 0.85, 95% CI: 0.60 - 1.00). In contrast, predicting control of hyperprolactinemia is challenging, in particular in terms of early follow-up (AUROC: 0.69, 95% CI: 0.50 - 0.83) vs. long-term follow-up (AUROC: 0.80, 95% CI: 0.58 - 0.97). It is of clinical importance that baseline prolactin levels are by far the most important outcome predictor at early follow-up, whereas remissions at 30 days dominate the ML prediction skill for DA-dependency over the long-term. CONCLUSIONS: This study highlights the performance benefits of combining a diverse set of classification algorithms to predict the outcome of first-line surgery in prolactinoma patients. We demonstrate the added benefit of considering two performance metrics jointly to assess the discrimination capacity of a diverse set of classifiers.

Long-term IGF-1 monitoring in prolactinoma patients treated with cabergoline might not be indicated.

PURPOSE: Cabergoline (CAB) therapy for prolactinomas has been associated with serum IGF-1 levels modifications, with recent reports indicating a paradoxical increase of IGF-1 levels during ongoing therapy. As a result, IGF-1 measurement has been proposed not only at diagnosis of a prolactinoma, but also during follow-up. In this follow-up study on prolactinoma patients with chronic CAB therapy, we investigated whether there are long-term changes in IGF-1 levels that necessitate continuous monitoring. METHODS: We reviewed our institutional database on prolactinoma patients with long-term CAB therapy, in whom IGF-1 levels were measured at baseline, at 3-months follow-up and in the long term. RESULTS: Chronic CAB therapy was noted in 20 patients (13 men, 7 women). Median (±SD) age was 43.5 ± 12.6 years. 17 (85%) patients presented with a macroprolactinoma. Median CAB treatment time was 75 ± 43 months (range 24-187). Median IGF-1 levels increased at last follow-up, though not significantly; from 122 ± 37 ng/ml (IQR 104-160 ng/ml) to 133 ± 54 (IQR 121-162 ng/ml), p = 0.10. Thereby, 18 (90%) patients showed normal serum IGF-1 levels adjusted for age, one (5%) patient above (1.05 × ULN) and 1 (5%) patient below the normal range (0.34 × ULN). No patient was or became symptomatic of acromegaly. CONCLUSION: Our long-term results indicate that chronic treatment with CAB in prolactinoma patients does not significantly modify serum IGF-1 levels. Bearing in mind the sample size of this study, continuing IGF-1 monitoring is not indicated in prolactinoma patients with long-term CAB therapy.

Persistent bone impairment despite long-term control of hyperprolactinemia and hypogonadism in men and women with prolactinomas.

While prolactinoma patients have high bone turnover, current data are inconclusive when it comes to determining whether correction of hyperprolactinemia and associated hypogandism improves osteodensitometric data in men and women over the long term. In a large cohort of including 40 men and 60 women, we studied the long-term impact of prolactinoma treatment on bone mineral density (BMD) in men versus women, assessed adverse effects of a primary surgical or medical approach, and evaluated data for risk factors for impaired BMD at last follow-up using multivariate regression analyses. Median duration of follow-up was 79 months (range 13-408 months). Our data indicate that the prevalence of impaired BMD remained significantly higher in men (37%) than in women (7%, p < 0.001), despite the fact that hyperprolactinemia and hypogonadism are under control in the majority of men. We found that persistent hyperprolactinemia and male sex were independent risk factors for long-term bone impairment. Currently, osteoporosis prevention and treatment focus primarily on women, yet special attention to bone loss in men with prolactinomas is advised. Bone impairment as "end organ" reflects the full range of the disease and could become a surrogate marker for the severity of long-lasting hyperprolactinemia and associated hypogonadism.

Impact of primary medical or surgical therapy on prolactinoma patients' BMI and metabolic profile over the long-term.

OBJECTIVES: High prolactin levels have been associated with weight gain and impaired metabolic profiles. While treatment with dopamine agonists (DAs) has been shown to improve these parameters, there is a lack of surgical series on its comparative effect in prolactinoma patients. METHODS: In this retrospective, comparative study, consecutive patients with a prolactinoma were enrolled if treated with first-line transsphenoidal surgery (TSS) or with DAs. Patients with prolactinomas of Knosp grade >2 and those with a follow-up <24 months were excluded, as were patients with missing laboratory metabolic parameters at baseline and over the long-term. Effects of either treatment on BMI and the metabolic profile were analyzed, and independent risk factors for long-term obesity were calculated. RESULTS: Primary treatment was TSS for 12 patients (40%) and DAs for 18 patients (60%). At diagnosis, no significant differences between the two cohorts were observed with regard to adenoma size, Knosp grading, baseline prolactin (PRL) levels, prevalence of hypogonadism, or laboratory metabolic parameters. Mean follow-up was 51.9 months (range, 24-158). Over the long-term, both TSS and DAs led to the control of hyperprolactinemia (92% vs. 72%) and hypogonadism (78% vs. 83%) in the majority of patients. While a significant decrease in patients' BMI and fasting glucose were observed, changes in the lipid profile were marginal and independent of the treatment modality. At baseline, increased BMI-but not the primary treatment strategy-was an independent predictor of long-term obesity. CONCLUSIONS: Over the long-term, patients' BMI and FG improve, but changes in the metabolic profile are marginal and independent of the primary treatment. It is presumable that not DAs per se, but rather the control of hyperprolactinemia plays a role in patients' metabolic profile alterations.

10-year follow-up study comparing primary medical vs. surgical therapy in women with prolactinomas.

While dopamine-agonists are the first-line approach in treating prolactinomas, surgery can be considered in selected cases besides non-responders or patients with dopamine-agonist intolerance. The aim of the present study was to compare the long-term outcome in women with prolactinomas treated primarily either surgically or medically who had not had prior dopamine-agonist treatment. Retrospective case-note study of all consecutive women with prolactinomas primarily managed with medical therapy or surgery in a tertiary referral centre. The clinical, biochemical, and radiological responses to first-line treatment at early and long-term follow-up were analysed. The primary therapeutic strategy was dopamine-agonists for 36 (34 %) and surgery for 71 (66 %) of the women. Baseline clinical and biochemical characteristics were not significantly different between the primary surgical and medical cohort. Median follow-up time was 90 months (range 13-408). Following primary treatment, prolactin level significantly decreased in both cohorts, on average to 13.5 µg/L (IQR 7-21; p < 0.001), and was within the normal range in 82 % of all patients. No women in the surgical cohort demonstrated permanent sequelae and morbidity was low. At final follow-up, control of hyperprolactinaemia required dopamine-agonist therapy in 64 % of women who had undergone primary medical therapy vs. 32 % of those who had primary surgical therapy (p = 0.003). Logistic regression revealed that the primary therapeutic strategy, but not adenoma size, was an independent risk factor for long-term dependence on dopamine-agonists. The present data indicate that in a dedicated tertiary referral centre, long-term control of hyperprolactinaemia in women with prolactinomas is high. In selected cases, a primary neurosurgical approach might at least be interdisciplinarily discussed with the primary goal of minimizing long-term dependence on dopamine-agonists.

Long-Term Follow-Up of Primary Medical Versus Surgical Treatment of Prolactinomas in Men: Effects on Hyperprolactinemia, Hypogonadism, and Bone Health.

OBJECTIVE: In men with prolactinomas, impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. Although dopamine agonists (DAs) are the first-line approach in prolactinomas, surgery can be considered in selected cases. In this study, we aimed to investigate the long-term control of hyperprolactinemia, hypogonadism, and bone health comparing primary medical and surgical therapy in men who had not had prior DA treatment. METHODS: This is a retrospective case-note study of 44 consecutive men with prolactinomas and no prior DAs managed in a single tertiary referral center. Clinical, biochemical, and radiologic response to the first-line approach were analyzed in the 2 cohorts. RESULTS: Mean age at diagnosis was 47 years (range, 22-78 years). The prevalence of hypogonadism was 86%, and 27% of patients had pathologic bone density at baseline. The primary therapeutic strategy was surgery for 34% and DAs for 66% of patients. Median long-term follow-up was 63 months (range, 17-238 months). Long-term control of hyperprolactinemia required DAs in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (P = 0.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathologic bone density was 37% at last follow-up, with no differences between the 2 therapeutic cohorts (P = 0.48). CONCLUSIONS: Despite control of hyperprolactinemia and hypogonadism in most patients independent of the primary treatment modality, the prevalence of impaired bone health status remains high, and osteodensitometry should be recommended.