Modifiable prognostic factors in uterine fibroid development: a systematic review of literature.

BACKGROUND: Many risk factors in uterine fibroid development have been identified, but women and their physicians are less aware of the influence of lifestyle on uterine fibroid development. The objective of this systematic review is to investigate and summarize modifiable prognostic factors associated with uterine fibroid development. METHODS: Pubmed and Embase were searched for relevant articles according to PRISMA guidelines. References from included articles were screened and when relevant also included. Human in vivo studies on modifiable factors in fibroid development were included. Studies on non-modifiable factors and treatment, in vitro studies and animal studies were excluded. 607 articles were screened and 33 articles were included. Two independent investigators collected data from the report. RESULTS: The strongest risk factor for fibroid development was a high BMI, while the strongest protective factors were a high fruit and vegetable intake and high vitamin D intake. CONCLUSION: More high-quality studies are necessary to better understand the impact of the abovementioned factors as well as the role they play in the growth of already existing fibroids.

Uterine fibroid development is multifactorial. Various non-modifiable and modifiable factors have been linked to uterine fibroid development. Modifiable factors are controllable by patients themselves. We performed a systematic review to investigate these modifiable factors. We screened 607 articles from 2 databases (PubMed and Embase) of which 33 were included in the review. We only included clinical studies on humans. A high body mass index (BMI) is found to be a modifiable risk factor for uterine fibroid development. Protective of uterine fibroid development are high fruit and vegetable intake and high vitamin D intake or sun exposure. More research is needed to investigate the applicability of these findings in clinical practice and to investigate the influence on the growth of already existing uterine fibroids.

Recurrence and survival after laparoscopy versus laparotomy without lymphadenectomy in early-stage endometrial cancer: Long-term outcomes of a randomised trial.

BACKGROUND: Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly when no lymphadenectomy is performed. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH), both without lymphadenectomy, for early-stage endometrial cancer up to 5 years postoperatively. METHODS: Follow-up of a multi-centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, grade, and radiotherapy with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. To test for significance, non-inferiority margins were defined. RESULTS: In total, 279 women underwent a surgical procedure, of whom 263 (94%) had follow-up data. For the TLH (n = 175) and TAH (n = 88) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.69; 95%CI, 0.31-1.52), OS (89.2% vs 82.8%; aHR[death], 0.60; 95%CI, 0.30-1.19), and DSS (95.0% vs 89.8%; aHR[death], 0.62; 95%CI, 0.23-1.70) were reported at 5 years. At a 10% significance level, and with a non-inferiority margin of 0.20, the null hypothesis of inferiority was rejected for all three outcomes. There were no port-site or wound metastases, and local recurrence rates were comparable. CONCLUSION: Disease recurrence and 5-year survival rates were comparable between the TLH and TAH groups and comparable to studies with lymphadenectomy, supporting the widespread use of TLH without lymphadenectomy as the primary treatment for early-stage, low-grade endometrial cancer.

Comparing volumetric and biochemical assessment of intravasation caused by hysteroscopic surgery.

BACKGROUND: During hysteroscopic surgery intravasation of irrigation fluid occurs, leading to potentially dangerous intravascular fluid overload. Currently, intravasation is usually measured volumetrically as fluid deficit. Intravasation could also be calculated using the decrease in hemoglobin or increase in chloride ion concentration, both phenomena known to result from intravasation. We compared the values of intravasation measured volumetrically as fluid deficit versus calculated from the biochemical change in hemoglobin and chloride. We expected that these values would show strong correlation and agreement. METHODS: In a retrospective data analysis of 51 patients who underwent hysteroscopic resection of myomas or endometrium a pre and post procedure concentration of haemoglobin and chloride was available. The fluid deficit was plotted against the two versions of calculated intravasation. Furthermore, we put the data into Bland-Altman plots to scrutinize their relationship. RESULTS: The volumetric assessed fluid deficit and both versions of biochemically assessed intravasation, either using the change in hemoglobin or chloride ion concentration, turned out to be three totally different entities with weak correlation. Bland-Altman plots show too wide limits of agreement, and a striking difference between the two methods of calculated intravasation. CONCLUSION: Our study shows significant differences and poor agreement between volumetric and biochemically assessed intravasation. Based on this study, routinely assessing intravasation by biochemical methods does not have additional benefit compared to the volumetric fluid deficit. It remains unclear which method resembles true intravasation.

Perioperative outcomes using LigaSure™ compared to conventional bipolar instruments in laparoscopic salpingo-oophorectomy: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the effects of LigaSure™ versus conventional bipolar techniques on operating time and blood loss during laparoscopic salpingo-oophorectomy in a randomized controlled trial. METHODS: In three teaching hospitals, 100 women undergoing a laparoscopic salpingo-oophorectomy were randomized for LigaSure or conventional bipolar instruments. Primary outcome was operating time (from initial skin incision to removal of the specimen). Secondary outcome measures were total operating time (from initial skin incision to skin closure), time to dissect the ovarian and infundibulopelvic ligaments, intraoperative blood loss, and subjective judgment of the instrument used. RESULTS: There were no differences in operating time and total operating time using LigaSure versus conventional bipolar instruments: 41.0 vs. 39.2 min (p = 0.78; 95 % CI = -10.9 to 14.5) and 54.6 vs. 58.6 min (p = 0.46; 95 % CI = -14.8 to 6.8), respectively. The mean blood loss using LigaSure versus conventional bipolar instruments was 38 vs. 33 mL (p = 0.73; 95 % CI = -22.7 to 32.2). Various subjective efficacy and instrument handling parameters of the two instruments varied among participating centers. CONCLUSION: There were no significant differences in operating time and blood loss with the use of LigaSure compared to conventional bipolar instruments during laparoscopic salpingo-oophorectomy, even after correction for potential confounders.

Effectiveness of a multidisciplinary care program on recovery and return to work of patients after gynaecological surgery; design of a randomized controlled trial.

BACKGROUND: Return to work after gynaecological surgery takes much longer than expected, irrespective of the level of invasiveness. In order to empower patients in recovery and return to work, a multidisciplinary care program consisting of an e-health intervention and integrated care management including participatory workplace intervention was developed. METHODS/DESIGN: We designed a randomized controlled trial to assess the effect of the multidisciplinary care program on full sustainable return to work in patients after gynaecological surgery, compared to usual clinical care. Two hundred twelve women (18-65 years old) undergoing hysterectomy and/or laparoscopic adnexal surgery on benign indication in one of the 7 participating (university) hospitals in the Netherlands are expected to take part in this study at baseline. The primary outcome measure is sick leave duration until full sustainable return to work and is measured by a monthly calendar of sickness absence during 26 weeks after surgery. Secondary outcome measures are the effect of the care program on general recovery, quality of life, pain intensity and complications, and are assessed using questionnaires at baseline, 2, 6, 12 and 26 weeks after surgery. DISCUSSION: The discrepancy between expected physical recovery and actual return to work after gynaecological surgery contributes to the relevance of this study. There is strong evidence that long periods of sick leave can result in work disability, poorer general health and increased risk of mental health problems. We expect that this multidisciplinary care program will improve peri-operative care, contribute to a faster return to work of patients after gynaecological surgery and, as a consequence, will reduce societal costs considerably. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2087.

The effect of transcervical resection of submucous fibroids on menstrual blood loss: A prospective cohort study.

OBJECTIVES: Transcervical resection of myoma (TCRM) is a widely implemented treatment for submucous fibroids. The aim of this study is to evaluate the effect of TCRM on menstrual bleeding, fibroid related symptoms and quality of life and hemoglobin (Hb) levels. STUDY DESIGN: A prospective cohort study was conducted in three teaching hospitals and two academic hospitals in the Netherlands. Patients with HMB (PBAC score > 150) and submucous fibroids (type 0, 1, 2, 3, 4 and hybrid type 2-5) scheduled for TCRM were eligible. At baseline and 3 months after TCRM a Trans Vaginal Ultrasound (TVU) was performed and a Hb sample was taken. Patients filled out the Pictorial Blood Assessment Chart (PBAC) and the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire at baseline and up to 6 months after surgery. Primary outcome was improvement in PBAC score 6 months after surgery. Secondary outcomes were improvement in PBAC score and Hb level 3 months after surgery and UFS-QOL scores 3 and 6 months after surgery. RESULTS: 126 patients were included and 104 were operated. PBAC were obtained from 98 patients. Six months after surgery, 56.6% of patients went from HMB to normal menstrual bleeding (PBAC < 150). A significant reduction in median PBAC scores of 427 (IQR 198 - 1392) (p <.0001) was found (86% improvement). UFS-QOL scores were obtained from 91 patients. Symptom severity improved from a median of 54 on a scale of 100 (IQR 44-66) at baseline to 22 (IQR 9-41) after 6 months (p <.0001) (59% improvement). Health related quality of life (HRQOL) improved from a median score of 44 on a scale of 100 (IQR 33-62) to 89 (IQR 67-97) 6 months after surgery (p <.0001) (102% improvement). CONCLUSION: TCRM significantly reduces the amount of menstrual bleeding, severity of fibroid related symptoms and improves HRQOL in patients with submucous fibroids.

Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL NL) in the Dutch population: a validation study.

OBJECTIVE: Uterine fibroids can cause a variety of symptoms in women, from heavy menstrual bleeding and dysmenorrhea to bulk symptoms. The Uterine Fibroid Symptom and health-related Quality Of Life questionnaire (UFS-QOL) is a patient-reported outcome measure developed for assessing fibroid-related symptoms in a standardised way. Our aim was to translate and validate the UFS-QOL in Dutch. DESIGN: Validation study. SETTING: Patients were recruited by a gynaecologist at the outpatient clinic. PARTICIPANTS: Women with uterine fibroids. METHODS: The UFS-QOL was translated into Dutch (UFS-QOL NL) and validated through testing construct validity (comprising of structural validity and hypotheses testing), reliability, responsiveness and interpretability, assessing floor and ceiling effects and minimal important change. An option to answer 'not applicable' was added to the translated questionnaire. RESULTS: 191 women with uterine fibroids completed the UFS-QOL NL at baseline, after 2 weeks and after 3 months. The questionnaire retained the same factor structure after translation (Comparative Fit Index 0.94-0.95; Tucker-Lewis fit Index 0.93-0.95; Root Mean Square Error of Approximation 0.10-0.11) and correlations to other questionnaires (RAND 36, Hospital Anxiety and Depression Scale and Golombok Rust Inventory of Sexual Satisfaction) were generally moderate, as hypothesised (Pearson's r 0.3-0.7). We found a sufficient reliability with intraclass correlation coefficients of approximately 0.8-0.9 for all subscales. Responsiveness was sufficient when testing hypotheses comparing women who had surgery with those who did not. Cronbach's alpha was higher than 0.7 for all subscales, indicating sufficient internal consistency and there were no concerns about floor or ceiling effects. Minimal important change could not be calculated due to low correlation between the different subscales and the anchor question. CONCLUSIONS: The results support the measurement properties of the Dutch UFS-QOL for assessing fibroid-related symptoms and health-related quality of life in Dutch women with uterine fibroids.

Electronic Continuous Pain Measurement vs Verbal Rating Scale in gynaecology: A prospective cohort study.

OBJECTIVE: To compare pain measured with a new electronic device - the Continuous Pain Score Meter (CPSM) - and the Verbal Rating Scale (VRS) during gynaecological procedures in an outpatient setting, and to correlate these outcomes with baseline anxiety and patient (in)tolerance to the procedure. STUDY DESIGN: This prospective cohort study was undertaken in two centres: a university hospital and a large teaching hospital in The Netherlands. Patients undergoing an outpatient hysteroscopy, colposcopy or ovum pick-up procedure for in-vitro fertilization in one of the two participating hospitals with availability of the CPSM were included. Pain was measured by both the CPSM and the VRS. Patient tolerance to the procedure was reported. Various outcomes of the CPSM were compared with those of the VRS and related to baseline anxiety scores. RESULTS: Ninety-one of 108 included patients (84 %) used the CPSM correctly during the procedure, and it was possible to analyse the CPSM scores for 87 women (81 %). The CPSM scores were all linearly related to the VRS. The peak pain score on the CPSM (CPSM-PPS) had the strongest correlation with the VRS score for all three procedures. Higher CPSM-PPS was related to patient (in)tolerance to the procedure (p = 0.03-0.002). Anxiety at baseline was not correlated with pain perception, except for VRS during colposcopy (r = 0.39, p = 0.016). CONCLUSION: The majority of patients were able to use the CPSM correctly, resulting in detailed information on pain perception for each individual pain stimulus during three outpatient gynaecological procedures. The CPSM-PPS had the strongest correlation with the VRS score and patient (in)tolerance to the procedure.

The HYSTER study: the effect of intracervically administered terlipressin versus placebo on the number of gaseous emboli and fluid intravasation during hysteroscopic surgery: study protocol for a randomized controlled clinical trial.

BACKGROUND: Transcervical resection of myoma or endometrium is a safe, hysteroscopic, minimally invasive procedure. However, intravasation of distension fluid is a common phenomenon during these procedures. In a previous study we observed venous gas emboli in almost every patient. The severity of hysteroscopic-derived embolization has been shown to be correlated to the amount of intravasation. In addition, paradoxical gas embolism, which is potentially dangerous, was observed in several patients. Studies have shown a reduction of intravasation by using intracervically administered vasopressin during hysteroscopy. We think that its analog, terlipressin, should have the same effect. In our previous research we observed more gaseous emboli as intravasation increased. Whether or not the insertion of intracervically administered terlipressin leads to a lower incidence and severity of gas embolism is unknown. We hypothesize that intracervically administered terlipressin leads to a reduction of intravasation with a lower incidence and severity of gas embolism. Terlipressin may be of benefit during hysteroscopic surgery. METHODS/DESIGN: Forty-eight patients (ASA 1 or 2) scheduled for transcervical resection of large, types 1-2 myoma or extensive endometrium resection will be included. In a double-blind fashion patients will be randomized 1:1 according to surgical treatment using either intracervically administered terlipressin or placebo. Transesophageal echocardiography will be used to observe and record embolic events. A pre- and post-procedure venous blood sample will be taken to calculate intravasation based on hemodilution. Our primary endpoint will be how terlipressin influences the severity of embolic events. Secondary endpoints include the effect of terlipressin on the amount of intravasation and on hemodynamic parameters. DISCUSSION: If terlipressin does indeed reduce the number of gaseous emboli and intravasation occurring during hysteroscopic surgery, it would be a simple method to minimize potential adverse events. It also allows for prolonged operating time before the threshold of intravasation is reached, thereby reducing the need for a second operation. TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), ID: NTR5577 . Registered retrospectively on 18 December 2015.

Effectiveness of an internet-based perioperative care programme to enhance postoperative recovery in gynaecological patients: cluster controlled trial with randomised stepped-wedge implementation.

OBJECTIVE: To evaluate the implementation and effectiveness of an internet-based perioperative care programme for patients following gynaecological surgery for benign disease. DESIGN: Stepped-wedge cluster randomised controlled trial. SETTING: Secondary care, nine hospitals in the Netherlands, 2011-2014. PARTICIPANTS: 433 employed women aged 18-65 years scheduled for hysterectomy and/or laparoscopic adnexal surgery. INTERVENTIONS: An internet-based care programme was sequentially rolled out using a multifaceted implementation strategy. Depending on the implementation phase of their hospital, patients were allocated to usual care (n=206) or the care programme (n=227). The care programme included an e-health intervention equipping patients with tailored personalised convalescence advice. MAIN OUTCOME MEASURES: The primary outcome was duration until full sustainable return to work (RTW). The degree of implementation of the care programme was evaluated at the level of the patient, healthcare provider and organisation by indicators measuring internet-based actions by patients and providers. RESULTS: Median time until RTW was 49 days (IQR 27-76) in the intervention group and 62 days (42-85) in the control group. A piecewise Cox model was fitted to take into account non-proportionality of hazards. In the first 85 days after surgery, patients receiving the intervention returned to work faster than patients in the control group (HR 2.66, 95% CI 1.88 to 3.77), but this effect was reversed in the small group of patients that did not reach RTW within this period (0.28, 0.17 to 0.46). Indicators showed that the implementation of the care programme was most successful at the level of the patient (82.8%) and professional (81.7%). CONCLUSIONS: Implementation of an internet-based care programme has a large potential to lead to accelerated recovery and improved RTW rates following different types of gynaecological surgeries. TRIAL REGISTRATION NUMBER: NTR2933; Results.

Two Cases of Endometrial Cancer in Twin Sisters with Myotonic Dystrophy.

We describe two cases of endometrial cancer (EC) occurring in nulligravid twin sisters with myotonic dystrophy. Both tested negative for Lynch syndrome and both were treated with laparoscopic hysterectomy with bilateral salpingooophorectomy and adjuvant radiotherapy. Although EC tends to run in families, the diagnosis in itself is not considered sufficient cause for screening or prophylactic measures in close relatives. However, the presence of additional risk factors, such as nulligravidity and myotonic dystrophy in the underlying cases, may call for extra vigilance in first-degree family members.

Predictors of successful surgical outcome in laparoscopic hysterectomy.

OBJECTIVE: To estimate, after correction for patient factors, to what extent blood loss, operative time, and adverse events are decisive factors for the successful outcome of laparoscopic hysterectomy. A secondary objective was to estimate to what extent a successful outcome can be predicted from surgical experience or other measures of surgical skill. METHODS: A nationwide multivariate 1-year cohort analysis was conducted with gynecologists who perform laparoscopic hysterectomy. The primary outcomes were blood loss, operative time, and adverse events. The procedures were corrected for multiple covariates in a mixed-effects logistic regression model. Furthermore, all primary outcomes were related to experience and the influence of individual surgical skills factors. RESULTS: One thousand five hundred thirty-four laparoscopic hysterectomies were analyzed for 79 surgeons. The success of the surgical outcome was significantly influenced by uterus weight, body mass index, American Society of Anesthesiologists Physical Status Classification, previous abdominal surgeries, and the type of laparoscopic hysterectomy. Surgical experience also predicted the successful outcome of laparoscopic hysterectomy with respect to blood loss and adverse events (P=.048 and .036, respectively). A significant improvement in surgical outcomes tends to continue up to approximately 125 procedures. Independently from surgical experience, an individual surgical skills factor was identified as odds ratio 1.67 and 3.60 for blood loss and operative time, respectively. CONCLUSION: After adjusting for risk factors, it was shown that an increase in experience positively predicted a successful outcome in laparoscopic hysterectomy with respect to blood loss and adverse events. However, the independent surgical skills factor shows a large variation in proficiency between individuals. The fact that a surgeon has performed many laparoscopic hysterectomies does not necessarily guarantee good surgical outcome. LEVEL OF EVIDENCE: II.