Introduction and hypothesis
Patient-reported outcome measures are fundamental tools when assessing effectiveness of treatments. The challenge lies in the interpretation: which magnitude of change in ...score is meaningful for the patients? The minimal important difference (MID) is defined as the smallest difference in score that patients perceive as important. The Patient Acceptable Symptom State (PASS) represents the value of score beyond which patients consider themselves well. We aimed to determine the MID and PASS for Pelvic Floor Distress Inventory-20 (PFDI-20) and Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6) in pelvic organ prolapse (POP) surgery.
Methods
We used data from 2704 POP surgeries from a prospective, population-based cohort. MID was determined with three anchor-based and one distribution-based method. PASS was defined using two different methods. Medians of the estimates were identified.
Results
The MID estimates with (1) mean change, (2) receiver-operating characteristic (ROC) curve, (3) 75th percentile, and (4) distribution-based method varied between 22.9–25.0 (median 24.2) points for PFDI-20 and 9.0–12.5 (median 11.3) for POPDI-6. The PASS cutoffs with (1) 75th percentile and (2) ROC curve method varied between 57.7–62.5 (median 60.0) for PFDI-20 and 16.7–17.7 (median 17.2) for POPDI-6.
Conclusion
A mean difference of 24 points in the PFDI-20 or 11 points in the POPDI-6 can be used as a clinically relevant difference between groups. Postoperative scores ≤ 60 for PFDI-20 and ≤ 17 for POPDI-6 signify acceptable symptom state.
Introduction and hypothesis
Various strategies are employed to manage stress urinary incontinence (SUI) during pelvic organ prolapse (POP) surgery. This study was aimed at facilitating shared ...decision-making by evaluating SUI symptom changes, staged SUI procedures, and their prognostic factors following POP surgery without concomitant SUI intervention.
Methods
We analyzed 2,677 POP surgeries from a population-based observational cohort, excluding patients with prior SUI surgery. The outcome measures were subjective SUI utilizing the Pelvic Floor Distress Inventory-20 questionnaire and number of subsequent SUI procedures. Multivariable linear models were applied to identify predictors of persistent SUI, procedures for persistent SUI, and de novo SUI. The primary assessment occurred at the 2-year follow-up.
Results
At baseline, 50% (1,329 out of 2,677) experienced SUI; 35% (354 out of 1,005) resolved, an additional 14% (140 out 1,005) improved, and 5.1% (67 out of 1,308) underwent a procedure for persistent SUI. De novo SUI symptoms developed in 20% (218 out of 1,087), with 3.2% (35 out of 1,087) reporting bothersome symptoms; 0.8% (11 out of 1,347) underwent a procedure for de novo SUI. High baseline symptom severity increased the risk of persistent SUI (adjusted odds ratio aOR 2.04, 95% confidence interval CI 1.65–2.53), whereas advanced preoperative apical prolapse decreased the risk (aOR 0.89, 95% CI 0.85–0.93). De novo SUI was more common with advancing age (aOR 1.03, 95% CI 1.01–1.05), baseline urgency urinary incontinence (aOR 1.21, 95% CI 1.06–1.38), and after transvaginal mesh surgery (aOR 1.93, 95% CI 1.24–3.00). It was not dependent on the compartment or preoperative degree of prolapse.
Conclusions
In a pragmatic setting, POP surgery results in a low rate of subsequent SUI procedures.
Defecation symptoms are common among women with pelvic organ prolapse. However, the relationship between posterior vaginal wall prolapse and defecation symptoms remains debatable. Even though there ...is a plausible biomechanical rationale for posterior wall prolapse to cause obstructed defecation, previous studies have drawn contradictory conclusions regarding the association.
We aimed to examine the association between posterior vaginal wall prolapse and defecation symptoms by assessing the following: (1) does prevalence of defecation symptoms increase along with posterior wall prolapse severity, (2) is postoperative symptom improvement greater in women who underwent posterior compartment procedures in comparison with those who did not, and (3) is symptom improvement related to the symptom’s correlation with the degree of prolapse?
We used data from a nationwide longitudinal cohort study with 3515 women undergoing pelvic organ prolapse surgery. We measured the prevalence of 9 defecation symptoms at baseline and at 6 and 24 months after surgery using the short form of the Pelvic Floor Distress Inventory. Baseline degree of prolapse was categorized in stages as defined by the Pelvic Organ Prolapse Quantification System. The relationship between the degree of posterior wall prolapse and prevalence of bothersome defecation symptoms was studied with logistic regression and adjusted for patient characteristics and severity of anterior wall and apical prolapse. Generalized estimating equations were used to assess the longitudinal change in symptom prevalence in groups of participants with and without repair for posterior vaginal compartment. Correlations between symptom improvement and symptom dependency on the degree of prolapse was assessed by calculating Pearson’s correlation coefficient.
The stage of posterior wall prolapse (stage 2 vs stage 0) correlated with splinting, straining, incomplete evacuation, fecal incontinence of liquid stool, pain during defecation, fecal urgency, and anorectal prolapse (adjusted odds ratios, 2.7, 2.1, 2.0, 1.5, 2.1, 1.4, and 2.2, respectively; P ≤ .007 for all). Flatal incontinence and fecal incontinence of solid stool were not associated with the severity of posterior vaginal wall prolapse. Obstructed defecation symptoms (splinting, straining, and incomplete evacuation) improved more in women undergoing posterior compartment surgery compared with women undergoing repair for other compartments. The greatest improvement at follow-up was observed for those symptoms that showed strongest association with the degree of prolapse at baseline.
Obstructed defecation symptoms are dependent on the posterior wall anatomy. Women presenting with posterior wall prolapse, and these symptoms can expect to improve after surgery. Other defecation symptoms also improve after pelvic organ prolapse surgery, but they are not as specific to posterior wall anatomy as obstructed defecation symptoms.
Introduction and hypothesis
It is unclear how compartment of pelvic organ prolapse (POP) impacts overactive bladder (OAB) symptom severity or improvement after POP surgery. We hypothesized that ...anterior and apical prolapse are more strongly associated with OAB symptoms than posterior compartment prolapse.
Methods
A total of 2933 POP surgeries from a prospective population-based cohort were divided into two groups: (1) anterior and/or apical compartment surgery (± posterior repair),
N
= 2091; (2) posterior repair only,
N
= 478. Urinary frequency and urgency urinary incontinence (UUI) were evaluated using PFDI-20 (bothersome symptom: score 3–4) at baseline, 6, and 24 months. Association between degree of POP in specific compartments and symptoms at baseline was estimated with generalized linear models and between compartment of surgery and symptom improvement with generalized estimating equations.
Results
At least one bothersome symptom was reported by 40% at baseline, 14% at 6, and 19% at 24 months. At baseline, urinary frequency was associated with degree of anterior and apical and UUI with anterior compartment prolapse. Women undergoing surgery for anterior/apical compartment started with worse symptoms and experienced greater improvement than women undergoing posterior compartment surgery. Bothersome frequency resolved in 82% after anterior/apical and in 63% after posterior compartment surgery. Bothersome UUI resolved in 75% after anterior/apical and in 61% after posterior compartment surgery. After surgery, symptom severity was comparable between groups. Bothersome de novo symptoms occurred in 1–3%.
Conclusions
OAB symptoms are more strongly related to anterior and apical than to posterior compartment prolapse, but improvement is seen after surgery for any vaginal compartment.
Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine ...leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found.
Although several validated generic health-related quality of life instruments exist, disease-specific instruments are important as they are often more sensitive to changes in symptom severity. It is ...essential to validate the instruments in a new population and language before their use. The objective of the study was to translate into Finnish the short forms of three condition-specific questionnaires (PFDI-20, PFIQ-7 and PISQ-12) and to evaluate their psychometric properties in Finnish women with symptomatic pelvic organ prolapse.
A multistep translation method was used followed by an evaluation of validity and reliability in prolapse patients. Convergent and discriminant validity, internal consistency and reliability via test-retest were calculated.
Sixty-three patients waiting for prolapse surgery filled the three questionnaires within two weeks. Response rate for each item was high in PFDI-20 and PISQ-12 (99.8 and 98.9% respectively). For PFIQ-7 response rate was only 60%. In PFIQ-7, six respondents (9.5%) reached the minimum value of zero showing floor effect. None of the instruments had ceiling effect. Based on the item-total correlations both PFIQ-7 and PFDI-20 had acceptable convergent validity, while the convergent validity of PISQ-12 was lower, r = 0.138-0.711. However, in this instrument only three questions (questions 6, 10 and 11) had r < 0.3 while others had r ≥ 0.380. In the test-retest analysis all the three instruments showed good reliability (ICC 0.75-0.92). Similarly, the internal consistency of the instruments, measured by Cronbach's α, was good (range 0.69-0.96) indicating high homogeneity.
Finnish validated translation of the PFDI-20 and PISQ-12 have acceptable psychometric properties and can be used for both research purposes and clinical evaluation of pelvic organ prolapse symptoms. The Finnish version of PFIQ-7 displayed low response rate and some evidence of a floor effect, and thus its use is not recommended in its current form.
This 5-yr follow-up study demonstrates that pelvic organ prolapse (POP) surgery improves sexual activity and reduces dyspareunia. Multiple factors, such as preoperative pain, prior POP surgery, and ...prolapse stage, may be associated with postoperative dyspareunia.
Even though surgery generally improves sexual function and alleviates dyspareunia related to pelvic organ prolapse (POP), knowledge of the long-term effects is scarce.
To describe changes in sexual activity and dyspareunia rates after POP surgery and to identify potential risk factors for the occurrence of dyspareunia.
This was a prospective longitudinal cohort study of women aged over 18 yr undergoing POP surgery in Finland during 2015. Out of 3515 participants, sexual activity and dyspareunia data were available at baseline, 6 mo, 2 yr, and 5 yr for 79%, 68%, 63%, and 57%, respectively.
Native tissue, transvaginal mesh, and abdominal mesh repair.
Rates of sexual activity and dyspareunia were assessed using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) at baseline and at 6 mo, 2 yr, and 5 yr after surgery. As a secondary outcome, risk factors for overall, persisting, and de novo dyspareunia were assessed using logistic regression models.
The proportion of sexually active women increased from 40.7% to 43% after surgery. Preoperative dyspareunia resolved in >50% of cases during the first 6 mo, irrespective of the surgical approach. De novo dyspareunia rates were low at all time points (1.9–3.1%). Several potential risk factors associated with preoperative and postoperative dyspareunia were identified: younger age, lower preoperative body mass index, lower prolapse stage at baseline, either pelvic pain or dyspareunia at baseline, prior surgery (stress urinary incontinence surgery, posterior colporrhaphy, POP surgery, hysterectomy), and posterior repair.
Dyspareunia is significantly reduced after POP repair irrespective of the surgical approach. However, multiple factors seem to be associated with persisting and de novo symptoms, which should be considered in preoperative counseling.
Our 5-year follow-up study demonstrates that surgery to repair pelvic organ prolapse (POP) in women improves sexual activity and reduces painful intercourse. Multiple factors, such as preoperative pain, previous POP surgery, and prolapse stage, may be associated with painful intercourse after surgery.
Objectives To study the outcome of various hysterectomies in 2 years 1996 (N =10110) and 2006 (N=5279). The hypothesis was that the change in operative practices in 10 years has resulted in ...improvements. Design 2 prospective nationwide cohort evaluations with the same questionnaire. Setting All national operative hospitals in Finland. Participants Patients scheduled to either abdominal hysterectomy (AH), vaginal hysterectomy (VH) or laparoscopic hysterectomy (LH) for benign disease. Outcome measures Patients’ characteristics, surgery-related details and complications (organ injury, infection, venous thromboembolism and haemorrhage). Results The overall complication rates fell in LH and markedly in VH (from 22.2% to 11.7%, p<0.001). The overall surgery-related infectious morbidity decreased in all groups and significantly in VH (from 12.3% to 5.2%, p<0.001) and AH (from 9.9% to 7.7%, p<0.05). The incidence of bowel lesions in VH sank from 0.5% to 0.1% and of ureter lesions in LH from 1.1% to 0.3%. In 2006 there were no deaths compared with three in 1996. Conclusions The rate of postoperative complications fell markedly in the decade from 1996 to 2006. This parallels with the recommendation of the recent meta-analyses by Cochrane collaboration; the order of preference of hysterectomies was for the first time precisely followed in this nationwide study. Trial registration The 2006 study was registered in the Clinical Trials of Protocol Registration System Data (NCT00744172).
Patient satisfaction and health-related quality of life are nowadays considered as the most important outcomes of pelvic organ prolapse treatment, and large, prospective clinical studies reporting ...the patient-reported surgical outcomes are needed.
To evaluate the effect of female pelvic organ prolapse surgery on health-related quality of life and patient satisfaction and to determine predictors of outcome.
This prospective nationwide cohort study consisted of 3515 women undergoing surgery for pelvic organ prolapse in 2015. The outcomes were measured by validated health-related quality of life instruments (generic 15D, Pelvic Floor Distress Inventory-20, and Patient Global Impression of Improvement) at 6 months and 2 years postoperatively. The baseline predictors of outcomes were studied with logistic regression analysis.
In total, 2528 (72%) women were eligible for analysis at 6 months and 2351 (67%) at 2 years. The mean change in the total 15D score suggested a clinically important improvement at 6 months but not at 2 years. However, an improvement in sexual activity, discomfort and symptoms, and excretion was observed during both follow-up assessments. Altogether, 77% and 72% of the participants reported a clinically significant improvement in Pelvic Floor Distress Inventory-20 at the 6-month and 2-year follow-ups, respectively. A total of 84% were satisfied with the outcome and 90% reported an improvement in comparison with the preoperative state with Patient Global Impression of Improvement-I. The strongest predictive factors for a favorable outcome were advanced apical prolapse (adjusted odds ratio, 2.06; 95% confidence interval, 1.58–2.70) and vaginal bulge (1.90, 1.30–2.80). Smoking was associated with an unfavorable outcome as measured by Patient Global Index of Improvement-I (1.69, 1.02–2.81).
Pelvic organ prolapse surgery improved health-related quality of life in 7 of 10 patients over a 2-year follow-up period, and patient satisfaction was high. Apical prolapse beyond the hymen and vaginal bulge were the most consistent predictors for improvement. Our results suggest that patients should be encouraged to stop smoking to avoid an unfavorable outcome.
One in four women suffers from uterine leiomyomas (ULs)-benign tumours of the uterine wall, also known as uterine fibroids-at some point in premenopausal life. ULs can cause excessive bleeding, pain ...and infertility
, and are a common cause of hysterectomy
. They emerge through at least three distinct genetic drivers: mutations in MED12 or FH, or genomic rearrangement of HMGA2
. Here we created genome-wide datasets, using DNA, RNA, assay for transposase-accessible chromatin (ATAC), chromatin immunoprecipitation (ChIP) and HiC chromatin immunoprecipitation (HiChIP) sequencing of primary tissues to profoundly understand the genesis of UL. We identified somatic mutations in genes encoding six members of the SRCAP histone-loading complex
, and found that germline mutations in the SRCAP members YEATS4 and ZNHIT1 predispose women to UL. Tumours bearing these mutations showed defective deposition of the histone variant H2A.Z. In ULs, H2A.Z occupancy correlated positively with chromatin accessibility and gene expression, and negatively with DNA methylation, but these correlations were weak in tumours bearing SRCAP complex mutations. In these tumours, open chromatin emerged at transcription start sites where H2A.Z was lost, which was associated with upregulation of genes. Furthermore, YEATS4 defects were associated with abnormal upregulation of bivalent embryonic stem cell genes, as previously shown in mice
. Our work describes a potential mechanism of tumorigenesis-epigenetic instability caused by deficient H2A.Z deposition-and suggests that ULs arise through an aberrant differentiation program driven by deranged chromatin, emanating from a small number of mutually exclusive driver mutations.
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