Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma.

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 infertility1, and are a common cause of hysterectomy2. They emerge through at least three distinct genetic drivers: mutations in MED12 or FH, or genomic rearrangement of HMGA23. 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 complex4, 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 mice5. 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.

Changes in Stress Urinary Incontinence Symptoms after Pelvic Organ Prolapse Surgery: a Nationwide Cohort Study (FINPOP).

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.

Recurrent pelvic organ prolapse after hysterectomy; a 10-year national follow-up study.

PURPOSE: Hysterectomy may be a risk factor for pelvic organ prolapse (POP). We assessed the risk of recurrent POP (operations and visits) after hysterectomy among women with previous POP. We also studied patient and operation related risk factors for POP recurrence. METHODS: This retrospective cohort study included 1697 women having previous POP diagnosis or POP at the time of hysterectomy (FINHYST 2006 cohort). Follow-up was until the end of 2016. The data was derived from the Finnish National Care register linked to the cohort. Hysterectomy approaches and other demographics were compared to the risk of a prolapse diagnosis and/or surgery. Cox regression model was used to identify hazard ratios. RESULTS: Following hysterectomy, a total of 280 women (16.5%) had a POP reoperation and 359 (21.2%) had an outpatient visit due to POP. Vaginal vault prolapse repair was the most common POP reoperation (n = 181, 10.7%), followed by anterior wall repair (n = 120, 7.1%). Median time to POP reoperation was 3.7 years. Hysterectomy approach did not affect reoperations or visits. Previous cesarean section and anterior repair during hysterectomy were associated with decreased risk, whereas concomitant sacrospinous fixation and uterus prolapse as the main indication led to increased risk of anterior/vault prolapse reoperations. Concomitant posterior repair decreased posterior reoperations and visits, but uterus weight over 500 g caused a fivefold increased risk of posterior prolapse visit. Residential status was associated with elevated risk of any POP reoperations and visits. CONCLUSIONS: Approximately one out of five women suffering from POP ensue POP reoperation or visit after hysterectomy. These high rates are independent on hysterectomy approach, but probably indicate that hysterectomy may worsen previous pelvic floor dysfunction.

Pelvic organ prolapse after hysterectomy: A 10-year national follow-up study.

INTRODUCTION: Hysterectomy may have an effect on the pelvic floor. Here, we evaluated the rates and risks for pelvic organ prolapse (POP) surgeries and visits among women with a history of hysterectomy for benign indication excluding POP. MATERIAL AND METHODS: In this retrospective cohort study 3582 women who underwent hysterectomy in 2006 were followed until the end of 2016. The cohort was linked to the Finnish Care Register to catch any prolapse-related diagnoses and operation codes following the hysterectomy. Different hysterectomy approaches were compared according to the risk for a prolapse, including abdominal, laparoscopic, laparoscopic-assisted vaginal and vaginal. The main outcomes were POP surgery and outpatient visit for POP, and Cox regression was used to identify risk factors (hazard ratios [HR]). RESULTS: During the follow-up, 58 women (1.6%) underwent a POP operation, of which a posterior repair was the most common (n = 39, 1.1%). Outpatient visits for POP symptoms occurred in 92 (2.6%) women of which posterior wall prolapses (n = 58, 1.6%) were the most common. History of laparoscopic-assisted vaginal hysterectomy were associated with risk for POP operation (HR 3.0, p = 0.02), vaginal vault prolapse operation (HR 4.3, p = 0.01) and POP visits (HR 2.2, p < 0.01) as compared to the approach of abdominal hysterectomy. History of vaginal deliveries and concomitant stress urinary continence operation were associated with the risk for a POP operation (HR 4.4 and 11.9) and POP visits (HR 3.9 and 7.2). CONCLUSIONS: Risk for POP operations and outpatient visits for POP symptoms in hysterectomized women without a preceding POP seems to be small at least 10 years after hysterectomy. History of LAVH, vaginal deliveries and concomitant stress urinary incontinence operations increased the risk for POP operations after hysterectomy. These data can be utilized in counseling women considering hysterectomy for benign indication.

Pelvic organ prolapse surgery and overactive bladder symptoms-a population-based cohort (FINPOP).

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.

Minimal important difference and patient acceptable symptom state for PFDI-20 and POPDI-6 in POP surgery.

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.

Pelvic organ prolapse surgery and quality of life-a nationwide cohort study.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Agreement between patient global impression scale of improvement, pelvic floor distress inventory and 15D in measuring the outcome of pelvic organ prolapse surgery.

AIMS: To evaluate the correlation between three commonly used patient-reported outcome measures, two generic and one condition-specific instrument, in assessing the change in health-related quality of life following pelvic organ prolapse surgery. METHODS: The generic health-related quality of life measure 15-dimensional instrument (15D), Patient Global Impression of Improvement (PGI-I), and prolapse-specific Pelvic Floor Distress Inventory (PDFI-20) were used to assess the effectiveness of pelvic organ prolapse surgery in the national FINPOP study of 3535 surgeries (83% of all pelvic organ prolapse operations) performed in Finland in 2015. Spearman correlations between PGI-I, change in 15D and its dimensions and change in PFDI-20 and its subscales over a 2-year follow-up were investigated. The proportion of concordant ratings was also studied by investigating the proportion of women rated similarly (worse/no change/better/much better) by two instruments according to validated cutoffs. RESULTS: Among 2248 women for whom the 2-year change in all instruments could be measured, changes in PFDI-20 and 15D and its dimensions were weak (ρ < 0.2 for all except excretion; ρ = 0.39 and sexual activity; ρ = 0.27). PFDI-20 change (ρ = 0.39) and its subscales (ρ = 0.19-0.40, all P < .001) were more strongly correlated with PGI-I. The proportion of fully concordant ratings were higher for PFDI-20 and PGI-I (50.6%) than for PFDI-20 and 15D (33.0%). CONCLUSION: The weak correlations between 15D, PGI-I, and PDFI-20 observed in this study show that the quantified health gains are strongly dependent on the chosen patient-reported outcome measures. This demonstrates the importance of using condition-specific sensitive outcome measures in assessing the impact of surgical treatment in pelvic organ prolapse.

Hysterectomy Provides Benefit in Health-Related Quality of Life: A 10-Year Follow-up Study.

STUDY OBJECTIVE: This study aims to evaluate short- and long-term effects of hysterectomy on health-related quality of life (HRQoL) and compare that with a representative age-standardized sample from the general population. DESIGN: A prospective survey as a part of FINHYST study. SETTING: Four Helsinki area hospitals. PATIENTS: Eight hundred thirty-six women with hysterectomy because of benign indications during 2006. INTERVENTIONS: A change in HRQoL assessed by the 15D instrument at baseline, and after 6 months and 10 years. The HRQoL of women was also compared with that of the age-standardized sample from the general female population. MEASUREMENTS AND MAIN RESULTS: Most hysterectomies were performed laparoscopically (41.8%), followed by vaginal (38.2%) and abdominal (20%) approaches. Indications were classified into 6 subgroups; myoma, abnormal uterine bleeding (AUB), endometriosis, pelvic organ prolapse (POP), adnexal mass, and precancerous lesions. The preoperative mean HRQoL in the patients was lower than that of the general population. In the whole study population, hysterectomy provided the greatest improvement in the dimensions of distress, vitality, discomfort and symptoms, and sexual activity, both short- and long-term. Those operated on for myoma, AUB, endometriosis, and POP showed an improved mean HRQoL after 6 months, whereas after 10 years in those operated on for myoma, AUB, and endometriosis, the HRQoL was still better than at baseline. Women with endometriosis never reached HRQoL of the general population. This is right, but the HRQoL of the general population remained lower than that of all other groups. CONCLUSION: Hysterectomy provided long-term improvement in HRQoL, especially in women with myoma, AUB, and endometriosis.

The relationship of defecation symptoms and posterior vaginal wall prolapse in women undergoing pelvic organ prolapse surgery.

BACKGROUND: 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. OBJECTIVE: 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? STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Methods of surgery for pelvic organ prolapse in a nationwide cohort (FINPOP 2015).

INTRODUCTION: The management of pelvic organ prolapse (POP) varies significantly between countries. The objective of this study was to describe the methods used for POP surgery in Finland and to identify the factors that affect clinicians' choice to use either a native tissue repair (NTR) or a mesh repair method. MATERIAL AND METHODS: This prospective cohort study included 3535 surgeries covering 83% of all POP operations performed in Finland in 2015. The operative details and patient characteristics, including the Pelvic Floor Distress Inventory (PFDI-20), were compared between three selected surgical methods: NTR, transvaginal mesh (TVM) and abdominal mesh (AM). The predictive factors for the use of mesh augmentation were also studied with logistic regression analysis. RESULTS: The most common method was NTR (n = 2855, 81%), followed by TVM (n = 429, 12%) and AM (n = 251, 7%). Approximately 92% of the patients who underwent primary prolapse surgery underwent NTR, and mesh surgery was used mainly for recurrent prolapse. The strongest predictor of mesh surgery was previous POP surgery for the same vaginal compartment (adjusted odds ratio [OR] = 56, 95% confidence interval [CI] = 38-84 for TVM; adjusted OR = 22, 95% CI = 14-34 for AM). Other predictive factors for mesh surgery were previous hysterectomy, healthcare district, severe bulge symptoms and advanced prolapse. TVM was associated with advanced anterior prolapse and older age. AM surgery was associated with advanced apical and/or posterior compartment prolapse. PFDI-20 scores were the highest in the AM group (108 vs 103 in the TVM group and 98 in the NTR group, P = 0.012), which indicates more bothersome symptoms than in the other groups. CONCLUSIONS: The Finnish practices follow international guidelines that advocate NTR as the principal surgical method for POP. Synthetic mesh augmentation was mainly used in patients with recurrent and advanced prolapse with severe symptoms. The variation in the rates of mesh augmentation for POP surgery in different hospitals implies a lack of sufficient evidence of the most suitable treatment method and indicates a need for national guidelines.

Validation of the short forms of the Pelvic Floor Distress Inventory (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) in Finnish.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Hysterectomies in Finland in 1990-2012: comparison of outcomes between trainees and specialists.

OBJECTIVE: To assess trends for hysterectomy methods in the Nordic countries and to compare outcomes of hysterectomies in Finland done by trainees with those done by specialists. DESIGN: Register-based study. SETTING: NOMESCO database for the Nordic countries and the Finnish Hospital Discharge Register. POPULATION: National prospective cohort of 5279 hysterectomies in Finland. METHODS: Numbers of hysterectomies in the Nordic countries were collected in 1995-2011 and in Finland in 1990-2012. The Finhyst study to collect data on hysterectomies for benign indications was carried out in Finland in 2006. Information concerning patients, surgeons, and hysterectomy outcome was analysed. MAIN OUTCOME MEASURES: Hysterectomy numbers and methods. Operating time, blood loss, and complications in hysterectomies done by trainees and specialists. RESULTS: In Finland, the rate of hysterectomies has been reduced by approximately 50% since the 1990s and is now similar to that in the other Nordic countries. The laparoscopic method is twice as common in Finland as in other Nordic countries, constituting 35-40% of all hysterectomies. The operating time for all hysterectomy methods was 16-25% longer among trainees than specialists. For the abdominal or laparoscopic methods there were no significant differences in the complication rates between the groups. In the vaginal approach, blood loss of ≥1000 mL was slightly more common in operations done by trainees (1.3% vs. 2.6%, p = 0.037). CONCLUSIONS: Laparoscopic hysterectomy is more common in Finland than in the other Nordic countries. Although trainees need more time to operate, there were no differences between the trainees and the specialists with regard to major complication rates.

Sexual Activity and Dyspareunia After Pelvic Organ Prolapse Surgery: A 5-Year Nationwide Follow-up Study.

Background: Even though surgery generally improves sexual function and alleviates dyspareunia related to pelvic organ prolapse (POP), knowledge of the long-term effects is scarce. Objective: To describe changes in sexual activity and dyspareunia rates after POP surgery and to identify potential risk factors for the occurrence of dyspareunia. Design setting and participants: 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. Intervention: Native tissue, transvaginal mesh, and abdominal mesh repair. Outcome measurements and statistical analysis: 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. Results and limitations: 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. Conclusions: 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. Patient summary: 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.

FINHYST, a prospective study of 5279 hysterectomies: complications and their risk factors.

BACKGROUND: Hysterectomy guidelines highlight an increase in urinary tract injuries with laparoscopic hysterectomy (LH). This national survey analyses complications of LH, abdominal hysterectomy (AH) and vaginal hysterectomy (VH). METHODS: A prospective cohort undergoing hysterectomy for benign indications during 2006 was drawn from 53 hospitals in Finland; all communal hospitals participated. Detailed questionnaires covered surgical data and intra- and post-operative major and minor complications, for which risk factors were analysed by a multivariate logistic regression model adjusted for surgical data and patient characteristics. RESULTS: Major complications rates in AH (n= 1255, 24%), LH (1679, 32%) and VH (2345, 44%) were 4.0, 4.3 and 2.6%, and total complications rates were 19.2, 15.4 and 11.7%, respectively. Logistic regression showed no statistically significant differences between approaches for any organ injuries or other major complications. Most bladder and bowel injuries (88 and 83%), but not ureter injuries (10%), were recognized intra-operatively. The ureter injury rate was low after LH (0.3%), as it was after other types of hysterectomy. Compared with LH, AH increased the odds of wound infection, and was an independent risk factor for urinary infections and febrile events. Compared with AH, LH and VH both presented a higher risk for pelvic infection; surgically treated equally often regardless of the type of hysterectomy. No differences in complications emerged between LH and VH. Obesity was a risk factor for many infections. Surgical adhesiolysis [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.38-4.21] was the strongest single risk factor for major complications as a whole. Bladder injury was associated with a history of caesarean section (OR 4.01, 95% CI 2.06-7.83) and with a large uterus ≥500 g (OR 2.88, 95% CI 1.05-7.90), while bowel injury was associated with adhesiolysis (OR 29.07, 95% CI 7.17-117.88). CONCLUSIONS: FINHYST is a large prospective hysterectomy study illustrating actual complications. Whenever possible, hysterectomy should be minimally invasive.

Parity associates with chromosomal damage in uterine leiomyomas.

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.

Complications of Pelvic Organ Prolapse Surgery in the 2015 Finnish Pelvic Organ Prolapse Surgery Survey Study.

OBJECTIVE: To describe the major complications of pelvic organ prolapse (POP) surgery in Finland. METHODS: The Finnish Pelvic Organ Prolapse Surgery Survey 2015 study is a prospective cohort of POP surgeries performed in Finland in 2015. Perioperative, postoperative, and late complications during 1 year of follow-up were compared among native tissue repair, transvaginal mesh, and abdominal mesh surgery. Major complications were assessed using the Clavien-Dindo grading system. Predictive factors for major complications were studied with logistic regression analysis. RESULTS: Within 1 year after POP surgery, 396 (11.2%) of 3,515 women had at least one complication: 10.9% after native tissue, 11.7% after transvaginal mesh, and 13.5% after abdominal mesh repair. The majority of complications occurred within 2 months after surgery and postoperative infection (4.3%) and bleeding or hematoma (2.6%) were the most frequent. The incidence of organ injuries was low. Mesh-augmented surgery was associated with significantly higher rates of bladder and bowel injuries than native tissue surgery. Complication-related reoperations occurred significantly more often after abdominal mesh repair than native tissue surgery (5.2% vs 1.8%, P=.001). Mesh-related complications were diagnosed more often after transvaginal mesh repair. The overall rate of major complications (Clavien-Dindo grades III-V) was 3.3%. Abdominal mesh surgery was associated with the highest rate of major adverse events (8.8% vs native tissue repair 2.6% and transvaginal mesh 4.9%). The incidence of Clavien-Dindo grade IV or V complications was rare (less than 0.6%). Mesh surgery (transvaginal mesh adjusted odds ratio [aOR] 2.23, 95% CI 1.31-3.80, and abdominal mesh aOR 3.02, 95% CI 1.67-5.46), longer operating time (aOR 2.84, 95% CI 1.78-4.53), prior POP surgery (aOR 1.68, 95% CI 1.00-2.81) and difficult surgery (aOR 2.75, 95% CI 1.63-4.62) were associated with an increased risk for occurrence of major complications. CONCLUSION: Serious adverse events were rare regardless of the operative approach. However, mesh-augmented surgery was associated with higher risk for major complications.

FINHYST 2006--national prospective 1-year survey of 5,279 hysterectomies.

BACKGROUND: In Finland, the number of hysterectomies during one decade has decreased by 34%. The national prospective FINHYST study in 1996 showed abdominal hysterectomy (AH) as being most common: 58%. In Finland since 2002, vaginal hysterectomy (VH) has been most preferred, with laparoscopic hysterectomy (LH) surpassing AH in 2005. METHODS: FINHYST 2006 is a national prospective hysterectomy study in which all hospitals collaborated from 1 January to 31 December 2006. Questionnaires, completed by gynaecologists, covered their experience, patient characteristics and surgical data. RESULTS: The 5279 hysterectomies distributed by approaches were 44% VHs, 32% LHs and 24% AHs. Less than 2% were subtotal. The main indications for hysterectomy were myomas (33%), uterine prolapse (28%) and menorrhagia (21%). The main indication for VH was not related to uterine prolapse in 39%. Bilateral salpingo-ooforectomy was performed in 36% of AHs, 32% of LHs and 2% of VHs. Antibiotic prophylaxis was used in 97%, and thrombosis prophylaxis in 65%. Haemorrhage was least and operation time shortest with VH, and hospital stay and sick leave were shortest after LH. CONCLUSIONS: In Finland, less invasive approaches comprise 76% of hysterectomies. This trend has resulted nationally in shortening of hospital stay and of convalescence time.

A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

Ten years of progress--improved hysterectomy outcomes in Finland 1996-2006: a longitudinal observation study.

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).