Sacrospinous hysteropexy versus vaginal hysterectomy with suspension of the uterosacral ligaments in women with uterine prolapse stage 2 or higher: multicentre randomised non-inferiority trial.

OBJECTIVE: To investigate whether uterus preserving vaginal sacrospinous hysteropexy is non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments in the surgical treatment of uterine prolapse. DESIGN: Multicentre randomised controlled non-blinded non-inferiority trial. SETTING: 4 non-university teaching hospitals, the Netherlands. PARTICIPANTS: 208 healthy women with uterine prolapse stage 2 or higher requiring surgery and no history of pelvic floor surgery. INTERVENTIONS: Treatment with sacrospinous hysteropexy or vaginal hysterectomy with suspension of the uterosacral ligaments. The predefined non-inferiority margin was an increase in surgical failure rate of 7%. MAIN OUTCOME MEASURES: Primary outcome was recurrent prolapse stage 2 or higher of the uterus or vaginal vault (apical compartment) evaluated by the pelvic organ prolapse quantification system in combination with bothersome bulge symptoms or repeat surgery for recurrent apical prolapse at 12 months' follow-up. Secondary outcomes were overall anatomical recurrences, including recurrent anterior compartment (bladder) and/or posterior compartment (bowel) prolapse, functional outcome, complications, hospital stay, postoperative recovery, and sexual functioning. RESULTS: Sacrospinous hysteropexy was non-inferior for anatomical recurrence of the apical compartment with bothersome bulge symptoms or repeat surgery (n=0, 0%) compared with vaginal hysterectomy with suspension of the uterosacral ligaments (n=4, 4.0%, difference -3.9%, 95% confidence interval for difference -8.6% to 0.7%). At 12 months, overall anatomical recurrences, functional outcome, quality of life, complications, hospital stay, measures on postoperative recovery, and sexual functioning did not differ between the two groups. Five serious adverse events were reported during hospital stay. None was considered to be related to the type of surgery. CONCLUSIONS: Uterus preservation by sacrospinous hysteropexy was non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments for surgical failure of the apical compartment at 12 months' follow-up. TRIAL REGISTRATION: trialregister.nl NTR1866.

Hysteropexy in the treatment of uterine prolapse stage 2 or higher: a multicenter randomized controlled non-inferiority trial comparing laparoscopic sacrohysteropexy with vaginal sacrospinous hysteropexy (LAVA-trial, study protocol).

BACKGROUND: Pelvic organ prolapse is a common health problem: the lifetime risk of undergoing surgery for pelvic organ prolapse by the age of 85 years is 19%. Pelvic organ prolapse has significant negative effects on a woman's quality of life. Worldwide, vaginal hysterectomy is the leading treatment method for patients with symptomatic uterovaginal prolapse. Several studies have shown that vaginal sacrospinous hysteropexy and laparoscopic sacrohysteropexy are safe and effective alternatives in treating uterine descent. To date, it is unclear which of these techniques leads to the best operative result and the highest patient satisfaction. Therefore, we conducted the LAVA trial. METHODS: The LAVA trial is a randomized controlled multicenter non-inferiority trial. The study compares laparoscopic sacrohysteropexy with vaginal sacrospinous hysteropexy in women with uterine prolapse stage 2 or higher. The primary outcome of this study is surgical success of the apical compartment at 1 and 5 years follow-up. Secondary outcomes are subjective improvement on urogenital symptoms and quality of life (assessed by disease-specific and general quality of life questionnaires), complications following surgery, hospital stay, post-operative recovery, sexual functioning and costs-effectiveness. Evaluation will take place pre-operatively, and 6 weeks, 6 months, 12 months and annually till 60 months after surgery. Validated questionnaires will be used.Analysis will be performed according to the intention to treat principle. Based on comparable recurrence rates of 3% and a non-inferiority margin of 10%, 62 patients are needed in each arm to prove the hypothesis with a 95% confidence interval. DISCUSSION: The LAVA trial is a randomized controlled multicenter non-inferiority trial that will provide evidence whether the efficacy of laparoscopic sacrohysteropexy is non-inferior to vaginal sacrospinous hysteropexy in women with symptomatic uterine prolapse stage 2 or higher. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR4029.

The challenge of implementing laparoscopic sacrocolpopexy.

Vaginal-vault prolapse is effectively treated using sacrocolpopexy (SCP). A randomized trial demonstrated that it can be performed as effectively via laparoscopy (LSCP) as via laparotomy and with less morbidity. This evidence begs the question of how units offering abdominal sacrocolpopexy will implement LSCP. Several limitations need to be overcome. LSCP initially requires longer operating time; however, that decreases with surgeon experience. To decrease operation time, suture training can be implemented ahead. Following a 15-h suturing lab, trainees achieved comparable operation times after 30 cases. Dissection is another critical time-consuming step and is difficult to model. Proficiency is more dependent on patient characteristics, though this component is poorly studied. One experience showed it takes 60 procedures to effectively limit complications. The large number of patients required for surgeon training for this relative infrequent operation creates a problem, thus limiting the number of centers available for training surgeons within a reasonable period.

Clomipramine concentration and withdrawal symptoms in 10 neonates.

AIM: After in utero exposure to tricyclic antidepressants, neonatal withdrawal symptoms have been reported with an estimated incidence between 20 and 50%; however, few data are available for clomipramine. This could also be the case for neonatal pharmacokinetic clomipramine parameters and so this study was set up. METHODS: Babies exposed to clomipramine in utero were included in an observational study, approved by the local ethics committee, after written informed consent. Withdrawal symptoms were scored at 12, 24 and 48 h after birth using the Finnegan score. Plasma concentrations were determined using an in-house-developed, validated liquid chromatography with mass detection (LC-MSMS) method at 0, 12, 24 and 48 h after birth. RESULTS: We found that three of 11 pregnancies were complicated with pre-eclampsia. Ten neonates were observed for clomipramine withdrawal symptoms. The observed withdrawal symptoms were too short a period of sleep after feeding (6), poor feeding (3), mild to severe tremors (6), hyperactive Moro reflex (3) and respiratory rate >60 breaths min(-1). Serious withdrawal reactions, such as tachycardia and cyanosis, were seen. We calculated a half-life value of 42 ± 16 h for clomipramine in neonates. Only a weak correlation was found between withdrawal reactions and clomipramine plasma concentration or desmethylclomipramine plasma concentration. CONCLUSIONS: In neonates, clomipramine is eliminated with a half-life value of 42 h, compared with 20 h in adults. In two of 10 neonates, tachycardia and cyanosis were seen as serious withdrawal symptoms after maternal use of clomipramine.

[Uterus preserving surgery versus vaginal hysterectomy in treatment of uterine descent: a systematic review]. / Uterussparende chirurgie versus vaginale hysterectomie als behandeling van descensus uteri.

OBJECTIVE: To compare the outcomes of uterus preserving procedures and vaginal hysterectomy in treatment of uterine prolapse. DESIGN: Systematic review. METHOD: We searched in Pubmed, Embase, the Cochrane Library and the reference lists of relevant publications for articles comparing uterus preserving procedures with vaginal hysterectomy. The following outcome measures were studied: anatomical result, subjective outcome regarding prolapse symptoms, micturition, defecation and sexual function, quality of life, duration of surgery, duration of hospital stay, amount of blood loss, complications and postoperative recovery. RESULTS: We found one systematic review, one randomised trial and five cohort studies, from which eight comparative studies were selected for review. There was no difference in subjective outcome after sacrospinous fixation, Manchester Fothergill procedure, abdominal hysteropexy and intravaginal slingplasty on comparison with vaginal hysterectomy. All procedures, except for sacrospinous ligament fixation, had similar anatomical outcomes to vaginal hysterectomy. With the exception of Manchester Fothergill procedure hospital stay was shorter after uterus preservation. The quality of most of the studies was poor, with only small numbers of patients included and short-term follow up. CONCLUSIONS: Although some uterus preserving procedures are associated with shorter operation time, shorter duration of hospital stay and less blood loss than vaginal hysterectomy, based on the current literature there is no clear preference for either uterus preserving surgery or hysterectomy in surgical treatment of uterine descent, since randomised trials of sufficient quality are lacking. Prospective clinical randomised trials with long term follow-up are needed to investigate the value of uterine preserving procedures.

One-day versus 3-day suprapubic catheterization after vaginal prolapse surgery: a prospective randomized trial.

INTRODUCTION AND HYPOTHESIS: For prolonged catheterization after vaginal prolapse surgery with anterior colporrhaphy, the optimal duration to prevent overdistention of the bladder remains unknown. We designed this study to determine the optimal length of catheterization. METHODS: We conducted a prospective randomized trial in which 179 women were allocated to 1-day or 3-day suprapubic catheterization. The primary outcome was the duration of catheterization. RESULTS: Mean duration of catheterization and hospital stay was significantly shorter in the 1-day catheterization group. The number of successful voiding trials was higher in the 3-day catheterization group (90.9% versus 79.3%), but this did not reach statistical significance. The percentage of urinary tract infection did not differ significantly between the groups (4.5% versus 2.4%). CONCLUSION: Starting a voiding trial 1 day after vaginal prolapse surgery leads to shorter duration of catheterization and hospital stay.

Treatment of uterine prolapse stage 2 or higher: a randomized multicenter trial comparing sacrospinous fixation with vaginal hysterectomy (SAVE U trial).

BACKGROUND: Pelvic organ prolapse is a common health problem, affecting up to 40% of parous women over 50 years old, with significant negative influence on quality of life. Vaginal hysterectomy is currently the leading treatment method for patients with symptomatic uterine prolapse. Several studies have shown that sacrospinous fixation in case of uterine prolapse is a safe and effective alternative to vaginal hysterectomy. However, no large randomized trials with long-term follow-up have been performed to compare efficacy and quality of life between both techniques.The SAVE U trial is designed to compare sacrospinous fixation with vaginal hysterectomy in the treatment of uterine prolapse stage 2 or higher in terms of prolapse recurrence, quality of life, complications, hospital stay, post-operative recovery and sexual functioning. METHODS/DESIGN: The SAVE U trial is a randomized controlled multi-center non-inferiority trial. The study compares sacrospinous fixation with vaginal hysterectomy in women with uterine prolapse stage 2 or higher. The primary outcome measure is recurrence of uterine prolapse defined as: uterine descent stage 2 or more assessed by pelvic organ prolapse quantification examination and prolapse complaints and/or redo surgery at 12 months follow-up. Secondary outcomes are subjective improvement in quality of life measured by generic (Short Form 36 and Euroqol 5D) and disease-specific (Urogenital Distress Inventory, Defecatory Distress Inventory and Incontinence Impact Questionnaire) quality of life instruments, complications following surgery, hospital stay, post-operative recovery and sexual functioning (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire). Analysis will be performed according to the intention to treat principle. Based on comparable recurrence rates of 3% and considering an upper-limit of 7% to be non-inferior (beta 0.2 and one sided alpha 0.025), 104 patients are needed per group. DISCUSSION: The SAVE U trial is a randomized multicenter trial that will provide evidence whether the efficacy of sacrospinous fixation is similar to vaginal hysterectomy in women with uterine prolapse stage 2 or higher. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1866.

A randomized, controlled trial comparing an innovative single incision sling with an established transobturator sling to treat female stress urinary incontinence.

PURPOSE: Mid urethral sling procedures have become the surgical treatment of choice for female stress urinary incontinence. Innovative modifications of mid urethral sling procedures were recently introduced with the claim of offering similar efficacy and decreased morbidity. We compared the efficacy and morbidity of an innovative single incision mid urethral tape and an established transobturator procedure. MATERIALS AND METHODS: We performed a prospective, randomized, controlled trial in 6 teaching hospitals in Belgium and The Netherlands between 2007 and 2009. A total of 96 patients received a TVT Secur™ single incision sling and 98 received a TVT™ Obturator System. We collected data on patient characteristics, surgery related parameters, adverse events, clinical followup, Urogenital Distress Inventory and SF-36® scores, validated questionnaires on daily life activities and visual analog scores objectifying pain. Followup was 1 year. RESULTS: One-year followup was available for 75 single incision sling and 85 obturator system cases. Stress urinary incontinence could be objectified in 16.4% of the patients with a single incision sling and in 2.4% with an obturator system (p <0.05). Stress urinary incontinence was subjectively reported by 24% of single incision sling and 8% of obturator system patients (p <0.05). One year after surgery the mean ± SD UDI incontinence domain score in the single incision sling and obturator system groups was 21 ± 24 and 13 ± 21, respectively (p <0.01). Patients with a single incision sling experienced significantly less pain during the first 2 weeks after surgery (p <0.05) and returned significantly earlier to normal daily activity. The OR of re-intervention for stress urinary incontinence 1 year after receiving a single incision sling vs an obturator system was 2.3 (95% CI 1.9-2.7). CONCLUSIONS: The single incision sling procedure is associated with less postoperative pain and a lower objective cure rate than the obturator system procedure.

Trocar-guided mesh compared with conventional vaginal repair in recurrent prolapse: a randomized controlled trial.

OBJECTIVE: To compare efficacy and safety of trocar-guided tension-free vaginal mesh insertion with conventional vaginal prolapse repair in patients with recurrent pelvic organ prolapse. METHODS: Patients with recurrent pelvic organ prolapse stage II or higher were randomly assigned to either conventional vaginal prolapse surgery or polypropylene mesh insertion. Primary outcome was anatomic failure (pelvic organ prolapse stage II or higher) in the treated vaginal compartments. Secondary outcomes were subjective improvement, effects on bother, quality of life, and adverse events. Questionnaires such as the Incontinence Impact Questionnaire and Urogenital Distress Inventory were administered at baseline, 6 months, and 12 months. Anatomic outcomes were assessed by an unblinded surgeon. Power calculation with α=0.05 and ß=0.80 indicated that 194 patients were needed. RESULTS: Ninety-seven women underwent conventional repair and 93 mesh repair. The follow-up rate after 12 months was 186 of 190 patients (98%). Twelve months postsurgery, anatomic failure in the treated compartment was observed in 38 of 84 patients (45.2%) in the conventional group and in eight of 83 patients (9.6%) in the mesh group (P<.001; odds ratio, 7.7; 95% confidence interval, 3.3-18). Patients in either group reported less bulge and overactive bladder symptoms. Subjective improvement was reported by 64 of 80 patients (80%) in the conventional group compared with 63 of 78 patients (81%) in the mesh group. Mesh exposure was detected in 14 of 83 patients (16.9%). CONCLUSION: At 12 months, the number of anatomic failures observed after tension-free vaginal mesh insertion was less than after conventional vaginal prolapse repair. Symptom decrease and improvement of quality of life were equal in both groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00372190. LEVEL OF EVIDENCE: I.

Protocol for the value of urodynamics prior to stress incontinence surgery (VUSIS) study: a multicenter randomized controlled trial to assess the cost effectiveness of urodynamics in women with symptoms of stress urinary incontinence in whom surgical treatment is considered.

BACKGROUND: Stress urinary incontinence (SUI) is a common problem. In the Netherlands, yearly 64.000 new patients, of whom 96% are women, consult their general practitioner because of urinary incontinence. Approximately 7500 urodynamic evaluations and approximately 5000 operations for SUI are performed every year. In all major national and international guidelines from both gynaecological and urological scientific societies, it is advised to perform urodynamics prior to invasive treatment for SUI, but neither its effectiveness nor its cost-effectiveness has been assessed in a randomized setting. The Value of Urodynamics prior to Stress Incontinence Surgery (VUSIS) study evaluates the positive and negative effects with regard to outcome, as well as the costs of urodynamics, in women with symptoms of SUI in whom surgical treatment is considered. METHODS/DESIGN: A multicentre diagnostic cohort study will be performed with an embedded randomized controlled trial among women presenting with symptoms of (predominant) SUI. Urinary incontinence has to be demonstrated on clinical examination and/or voiding diary. Physiotherapy must have failed and surgical treatment needs to be under consideration. Patients will be excluded in case of previous incontinence surgery, in case of pelvic organ prolapse more than 1 centimeter beyond the hymen and/or in case of residual bladder volume of more than 150 milliliter on ultrasound or catheterisation. Patients with discordant findings between the diagnosis based on urodynamic investigation and the diagnosis based on their history, clinical examination and/or micturition diary will be randomized to operative therapy or individually tailored therapy based on all available information. Patients will be followed for two years after treatment by their attending urologist or gynaecologist, in combination with the completion of questionnaires. Six hundred female patients will be recruited for registration from approximately twenty-seven hospitals in the Netherlands. We aspect that one hundred and two women with discordant findings will be randomized. The primary outcome of this study is clinical improvement of incontinence as measured with the validated Dutch version of the Urinary Distress Inventory (UDI). Secondary outcomes of this study include costs, cure of incontinence as measured by voiding diary parameters, complications related to the intervention, re-interventions, and generic quality of life changes. TRIAL REGISTRATION: Clinical Trials NCT00814749.

Secondary colposuspension: results of a prospective study from a tertiary referral centre.

OBJECTIVE: To evaluate the results of secondary colposuspension in women with recurrent urinary stress incontinence. DESIGN: Prospective cross sectional observational study. SETTING: Tertiary referral urogynaecology unit. POPULATION: Fifty-six women with recurrent stress incontinence. MAIN OUTCOME MEASURES: Determine prognostic factors that may affect the outcome of surgery, long term subjective and objective success rates and identify complications of secondary colposuspension. RESULTS: The mean age was 54 years (range 34-83) and the median parity was 3 (range 1-5). The median length of follow up was four years (range 1.01-7.07). Forty-two (75%) women had genuine stress incontinence and 14 (25%) had mixed incontinence on subtracted cystometry. The subjective cure rate was 71% and the objective cure rate was 80% and, as per Kaplan-Meier life time analysis, 65% had not failed surgery five years after the operation. The complication rate was low. However at follow up, eight women had required a posterior colporrhaphy for rectocele and three had a sacrocolpopexy for vault prolapse. Another eight women required further treatment for stress incontinence (seven urethral bulking agents and one tension-free vaginal tape). There was no correlation of the outcome to age, past hysterectomy, number of previous incontinence procedures, parity, body mass index or blood loss at operation. CONCLUSION: Colposuspension after failed continence surgery has a good outcome with a low complication rate, but many still require further surgery for prolapse.