Pelvic Organ Prolapse Recurrence Clinical Trial
Official title:
The Efficacy of Laparoscopic Sacrocolpopexy in the Treatment of Pelvic Organ Prolapse in Women With or Without Avulsion of the Levator Ani Muscle
Based on a prospective study, to evaluate how pre-operative pelvic floor status - the presence of injury to the musculus levator ani - may influence the results of laparoscopic sacrocolpopexy. The investigators hope to confirm or disprove the hypothesis that the presence of such injury increases the risk of post-operative prolapse recurrence
Introduction Pelvic organ prolapse (POP), is a common health problem affecting up to 40% of
women. The life time risk for undergoing at least one session of pelvic organ prolapse
surgery has been estimated at approximately 13%. The prevalence of reoperation after primary
pelvic reconstructive surgery is high, around 30%, while some articles report the figure as
up to 58%. From the beginning of the 1990s the view of pelvic floor defects and urinary
incontinence in women started to change significantly. The diagnostics and management of
these defects became an independent uro-gynecological sub-specialization within gynecology
and obstetrics, and it has been included among 4 basic sub-specializations recognized by the
European Board and College of Obstetrics and Gynecology. Surgical treatment is indicated in
women with symptomatic POP when conservative management has failed or has been declined.
There is no indication for repair of asymptomatic POP as an isolated procedure where
surgical correction is of uncertain benefit and adds peri- and post-operative risks. The
objective of our treatment should always aim to restore quality of life and comfort. Very
little is known of the factors associated with surgical failure. Studies have identified a
variety of risk factors: younger age, high body mass index and advanced preoperative
prolapse (grade III-IV) were associated with an increased risk of reoperation in some
studies, while other studies did not prove these hypotheses. One factor which significantly
influences the result of the pelvic organ surgery is the presence of pelvic floor injury.
Injury of the levator ani muscle mainly affects the results of traditional vaginal wall
repair, with 60% risk of recurrence. In the last few years, in an attempt to reduce
recurrence and improve the outcome of reconstructive surgery in the treatment of pelvic
organ prolapse, surgeons have started to use transvaginally introduced prosthetic material
(mesh). This type of surgery significantly increases the efficacy of the procedure (anatomic
cure rate over 90%), but its use is associated with a risk of some complications (vaginal
erosions and potential consecutive infections, granulomas, dyspareunia, vesico-vaginal
fistulas, chronic pain) thereby potentially reducing the patients' quality of life and
leading to additional surgery. If the mesh is introduced during the sacrocolpopexy and the
vaginal wall is not open, there is a significant decrease of mesh-related complications.
Laparoscopic sacrocolpopexy is considered the gold standard for the management of apical
prolapse with high long-term efficacy. Based on the retrospective data available, it seems
that the status of the pelvic floor may also influence the results of this procedure, but at
present investigators have no data to confirm this hypothesis. Therefore investigators plan
to obtain these data from a prospective analysis of the results of laparoscopic
sacrocolpopexy.
For the prospective longitudinal study, the investigators plan to include all patients for
whom surgical treatment of pelvic organ prolapse and laparoscopic sacrocolpopexy are
indicated. Based on pre-study power analysis enrollment of 120 patients is planned (after
preliminary evaluation of the results this could be increased to 160 patients), which is the
minimal number to prove or disprove the null hypothesis: The pelvic floor does not influence
the result of laparoscopic sacrocolpopexy in women with symptomatic pelvic organ prolapse
stage II or higher. Based on previous studies it can be anticipated that the failure rate in
patients with a defect of the pelvic floor will be higher. To enroll an adequate number of
patients the study will be conducted in two university centers with long experience of this
type of surgery (the number of enrolled patients in each workplace should be identical).
Based on pre-study statistical calculations (power analysis) it is indicated that the
required sample size for final statistical analysis in each group is 54 patients (allocation
ratio 1:1). Investigators estimate a drop-out rate of 10%, therefore it is planned to enroll
60 patients into each group.
Aim of the study Based on a prospective study, to evaluate how pre-operative pelvic floor
status - the presence of injury to the musculus levator ani - may influence the results of
laparoscopic sacrocolpopexy. The investigators hope to confirm or disprove the hypothesis
that the presence of such injury increases the risk of post-operative prolapse recurrence.
Inclusion criteria are:
Age over 18, signed informed consent, symptomatic pelvic organ prolapse stage II or higher
(according to the International Continence Society Pelvic Organ Prolapse quantification
system - POPQ) in anterior and apical (central) compartment, and agreement with
postoperative follow-up.
Exclusion criteria are:
Previous pelvic reconstructive surgery with mesh, isolated posterior compartment prolapse,
previous radiotherapy in lesser pelvis, contraindication for laparoscopic sacrocolpopexy.
Pre-operative assessment.
All patients will undergo complete urogynecological investigation before the procedure:
history, clinical examination, assessment of pelvic organ prolapse using the POPQ system,
examination of the levator resting tone and contraction (Oxford scale),where appropriate
urodynamics according to International Continence Society recommendation and ultrasound
examination. They will also complete standardized international questionnaires (ICIQ-UI SF,
PISQ 12, POPDI). Ultrasound examinations will be performed as a combined examination using a
convex probe, from abdominal and perineal approaches, and sectoral vaginal probe from the
introital approach. The study will be recorded mainly in digital form. Acquired data from 4D
imagery will be preserved in form of data set and processed with the appropriate proper
software. The ultrasound examination will include an assessment of standard parameters
describing position of urethrovesical junction, bladder descent, uterus descent, posterior
vaginal wall descent (rectocele, enterocele). Using 3D/4D ultrasound examination the status
of pelvic floor will be evaluated (presence of avulsion of puborectalis muscle, abnormal
genital hiatus distension). Based on pre-operative ultrasound examination, the women will be
divided into two groups:
1. Group - women without defect of pelvic floor with urogenital hiatus size up to 30 cm2
2. Group - women with pelvic floor trauma with urogenital hiatus size over 30 cm2
Surgery and peri-operative monitoring All surgical procedures will be provided under general
anesthesia, and antibiotic prophylaxis will be used. Surgery will be provided in
standardized steps: identification of the promontory, dissection of the peritoneum above the
promontory and preparation of the ligamentum longitudinale anterior, peritoneum dissection,
dissection of the vesicovaginal septum up to bladder neck, dissection of the rectovaginal
septum towards the perineum, application of Y mesh, fixation to the vaginal apex using the
non-absorbable sutures, and for anterior and posterior vaginal wall absorbable sutures
fixation of the upper mesh arm to the ligamentum longitudinale anterior using non-absorbable
suture, following by complete peritoneum closure above the mesh. The procedure could include
salpingo-oophorectomy, supracervical hysterectomy or total hysterectomy (concomitant
procedures are not exclusion criteria).
Any peri-operative complications will be monitored. Surgical evaluation will include
operating time (from incision to last suture), estimated intraoperative blood loss (vacuum
aspiration), and perioperative complications (bladder perforation, vagina perforation, bowel
injury, ureter injury and vascular injury). Postoperative data will be analyzed, including
early postoperative complications (hematoma, spontaneous voiding recovery, urinary tract
infection, ileus, constipation) and late postoperative complications (procedure failure,
mesh erosion, de novo voiding difficulty, de novo stress urinary incontinence, further
surgical procedures).
Post-operative follow-up The first post-operative complete examination is planned for 3
months after surgery (the same examination as before the procedure). The next check-up will
be provided one year and two years after surgery, and the procedure will be the same as at
the 3-month check-up. In addition to pre-operative ultrasound examination, the position of
the mesh will be monitored. We plan to have a minimum one year follow-up for all patients in
this study, and also after two years when possible. Postoperative follow-up will be
terminated if the result of surgery is evaluated as a failure, and in these cases
reoperation will be offered. We also plan further post-operative follow-up up to five years.
Criteria for evaluation of the cure and failure:
Primary outcome: the objective cure will be defined as absence of pelvic organ prolapse
(using the POPQ system - maximal I. stage prolapse).
Number of failures in each group: failure is defined as pelvic organ prolapse stage II or
higher using the POPQ system during the clinical examination, or as a descent 1 cm below the
lower edge of the pubic bone based on ultrasound examination .
Secondary outcome:
These include change of the genital hiatus size, distance of mesh from the bladder neck
urethrovesical junction), lowest position of the mesh, evaluation of the subjective
parameters, quality of life based on evaluation of questionnaires ICIQ-SF, PISQ 12, POPDI,
occurrence of de novo stress urinary incontinence, number of re-operations for pelvic organ
prolapse, occurrence de novo symptoms of overactive bladder, in sexually active patients
occurrence of de novo dyspareunia
Our project completely fulfills the primary aims in conception of health research till the
year 2022, in the subfield "Innovative surgical procedure". Basic aims and priorities of the
project are: implementation of the surgical procedures with lower invasivity to the
treatment of pelvic organ prolapse and predict its efficacy on pre-operative pelvic floor
status, minimizing unfavorable impact of the surgical procedure on the patient. Basis for
the evaluation of the socio-economic contribution of the project solution will be
high-quality evaluation of modern surgical procedures. Implementation of the new effective
procedures for the pelvic organ prolapse shall significantly decrease total treatment cost,
and significantly improve the long term quality of life of the patient. Thus is necessary to
conduct such type of study, in order to use only those procedures which improve or maintain
treatment effectiveness, do not increase the complication rate, and decrease the recovery
time - thus having a fundamental impact on the amount of money invested from the public
budget.
d) Methods promotion For a comparison of two groups of patient, with or without pelvic floor
injury is estimated range selections in particular groups. If we mark p1 percentage of
success rate procedure in patient with pelvic floor injury, p2 percentage of success rate
procedure in the group without pelvic floor injury, for a 5% significance level we will
prove zero hypothesis (that the percentage success rate is in all groups same) or the
alternative hypothesis (that the percentage success rate differ). We require the ranges of
selection to be the same in all groups same, and for percent values p1=85%, P2=60% a we
require power test 80%. Under these conditions statistical calculations indicate that the
required sample size in each group is 54 patients, and so as a whole we will analyze the
data of almost 108 patients. We estimate a drop-out rate of 10%, so it is planned to
enrolled 60 patients into each group- total 120 patients. The success rate used to calculate
the size of the group has been estimated from previous studies; the estimated success rate
of 60% for the patient with pelvic floor defect, and higher efficacy in patient with normal
pelvic floor (85%). After evaluation of one year result of 60 women we plan to provide
interim analysis and re-calculated the numbers of women which should be enrolled to the
study to reach the statistical significance, and we are able to increase the number of
enrolled women up to 20 in each center to total number of 160 included patients. Based on a
statistical model, special software for data input will be prepared. The values to be
monitored will be exactly specified in the model to allow for subsequent statistical
processing. In our study we will use several types of statistical evaluation. In the tables
summarizing general characteristics, data will be evaluated by means of data average and
median, significant deviation. Furthermore, we will establish floor and cap of 95%
confidence interval to arrive at an average. Zero or alternative hypotheses will be
established and their validity determined. Where numbers are compared, chi square will be
applied, while in cases where the number of observations is small, Fischer exact test will
be used. We will be used non-parametric Kruskal-Wallis one-way analysis of variance for
quantitative features and Fisher exact test for contingency tables. We used Bonferroni
inequality to correct p value in case of multiple comparisons.
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