What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers.

OBJECTIVE: To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids. MATERIALS AND METHODS: In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes. RESULTS: Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01). CONCLUSION: Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother. CLINICAL RELEVANCE STATEMENT: Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid. TRIAL REGISTRATION: Clinical trial ID: NCT01285960. KEY POINTS: • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.

Evaluation of the routine use of pelvic MRI in women presenting with symptomatic uterine fibroids: When is pelvic MRI useful?

BACKGROUND: Pelvic ultrasound (US) diagnosis of uterine fibroids may overlook coexisting gynecological conditions that contribute to women's symptoms. PURPOSE: To determine the added value of pelvic MRI for women diagnosed with symptomatic fibroids by US, and to identify clinical factors associated with additional MRI findings. STUDY TYPE: Retrospective observational study. POPULATION: In all, 367 consecutive women with fibroids diagnosed by US and referred to our multidisciplinary fibroid center between 2013-2017. FIELD STRENGTH/SEQUENCE: All patients had both pelvic US and MRI prior to their consultations. MRIs were performed at 1.5 T or 3 T and included multiplanar T2 -weighted sequences, and precontrast and postcontrast T1 -weighted imaging. ASSESSMENT: Demographics, symptoms, uterine fibroid symptom severity scores, and health-related quality of life scores, as well as imaging findings were evaluated. STATISTICAL TESTS: Patients were separated into two subgroups according to whether MRI provided additional findings to the initial US. Univariate and multivariate regression analyses were performed. RESULTS: Pelvic MRI provided additional information in 162 patients (44%; 95% confidence interval [CI] 39-49%). The most common significant findings were adenomyosis (22%), endometriosis (17%), and partially endocavitary fibroids (15%). Women with pelvic pain, health-related quality of life scores less than 30 out of 100, or multiple fibroids visualized on US had greater odds of additional MRI findings (odds ratio [OR] 1.68, 2.26, 1.63; P = 0.02, 0.004, 0.03, respectively), while nulliparous women had reduced odds (OR 0.55, P = 0.01). Patients with additional MRI findings were treated less often with uterine fibroid embolization (14% vs. 36%, P < 0.001) or MR-guided focused US (1% vs. 5%, P = 0.04), and more often with medical management (17% vs. 8%, P = 0.01). DATA CONCLUSION: Pelvic MRI revealed additional findings in more than 40% of women presenting with symptoms initially ascribed to fibroids by US. Further evaluation using MRI is particularly useful for parous women with pelvic pain, poor quality of life scores, and/or multiple fibroids. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019.

Are fibroid and bony pelvis characteristics associated with urinary and pelvic symptom severity?

BACKGROUND: Urinary and pelvic floor symptoms often are attributed to size and location of uterine fibroid tumors. However, direct supporting evidence that links increased size to worsening symptoms is scant and limited to ultrasound evaluation of fibroid tumors. Because management of fibroid tumors is targeted towards symptomatic relief, the identification of fibroid and pelvic characteristics that are associated with worse symptoms is vital to the optimization of therapies and prevention needless interventions. OBJECTIVE: We examined the correlation between urinary, pelvic floor and fibroid symptoms, and fibroid size and location using precise uterine fibroid and bony pelvis characteristics that were obtained from magnetic resonance imaging. STUDY DESIGN: A retrospective review (2013-2017) of a multidisciplinary fibroid clinic identified 338 women who had been examined via pelvic magnetic resonance imaging, Pelvic Floor Distress Inventory questionnaire (score 0-300), and a Uterine Fibroid Symptoms questionnaire (score 1-100). Multiple linear regression analysis was used to assess the influence of clinical factors and magnetic resonance imaging findings on scaled Pelvic Floor Distress Inventory and Uterine Fibroid Symptoms scores. Data were analyzed with statistical software. RESULTS: Our cohort of 338 women had a median Pelvic Floor Distress Inventory of 72.7 (interquartile range, 41-112.3). Increased Pelvic Floor Distress Inventory score was associated with clinical factors of higher body mass index (P<.001), noncommercial insurance (P<.001), increased parity (P=.001), and a history of incontinence surgery (P=.003). Uterine volume, dominant fibroid volume, dimension and location, and fibroid tumor location relative to the bony pelvis structure did not reach significance when compared with pelvic floor symptom severity. The mean Uterine Fibroid Symptoms score was 52.0 (standard deviation, 23.5). An increased Uterine Fibroid Symptoms score was associated with dominant submucosal fibroid tumors (P=.011), body mass index (P<.0016), and a clinical history of anemia (P<.001) or any hormonal treatment for fibroid tumors (P=.009). CONCLUSION: Contrary to common belief, in this cohort of women who sought fibroid care, size and position of fibroid tumors or uterus were not associated with pelvic floor symptom severity. Whereas, bleeding symptom severity was associated with dominant submucosal fibroid tumor and previous hormonal treatment. Careful attention to clinical factors such as body mass index and medical history is recommended when pelvic floor symptoms are evaluated in women with uterine fibroid tumors.

Impact of the 2014 Food and Drug Administration Warnings Against Power Morcellation.

STUDY OBJECTIVE: To determine whether members of the AAGL Advancing Minimally Invasive Gynecologic Surgery Worldwide (AAGL) and members of the American College of Obstetricians and Gynecologists Collaborative Ambulatory Research Network (ACOG CARN) have changed their clinical practice based on the 2014 Food and Drug Administration (FDA) warnings against power morcellation. DESIGN: A survey study. SETTING: Participants were invited to complete this online survey (Canadian Task Force classification II-2). PATIENTS: AAGL and ACOG CARN members. INTERVENTIONS: An online anonymous survey with 24 questions regarding demographics and changes to clinical practice during minimally invasive myomectomies and hysterectomies based on the 2014 FDA warnings against power morcellation. MEASUREMENTS AND MAIN RESULTS: A total of 615 AAGL members and 54 ACOG CARN members responded (response rates of 8.2% and 60%, respectively). Before the FDA warnings, 85.8% and 86.9%, respectively, were using power morcellation during myomectomies and hysterectomies. After the FDA warnings, 71.1% and 75.8% of respondents reported stopping the use of power morcellation during myomectomies and hysterectomies. The most common reasons cited for discontinuing the use of power morcellation or using it less often were hospital mandate (45.6%), the concern for legal consequences (16.1%), and the April 2014 FDA warning (13.9%). Nearly half of the respondents (45.6%) reported an increase in their rate of laparotomy. Most (80.3%) believed that the 2014 FDA warnings have not led to an improvement in patient outcomes and have led to harming patients (55.1%). CONCLUSION: AAGL and ACOG CARN respondents reported decreased use of power morcellation during minimally invasive gynecologic surgery after the 2014 FDA warnings, the most common reason cited being hospital mandate. Rates of laparotomy have increased. Most members surveyed believe that the FDA warnings have not improved patient outcomes.

Clinical utility of postoperative hemoglobin level testing following total laparoscopic hysterectomy.

OBJECTIVE: To determine the clinical utility of hemoglobin level testing in guiding postoperative care following total laparoscopic hysterectomies performed for benign indications. STUDY DESIGN: Retrospective cohort study. RESULTS: A total of 629 women underwent total laparoscopic hysterectomies during the 24 month study period. Only 16 (2.5%) developed symptoms and/or signs suggestive of hemodynamic compromise. When compared to asymptomatic patients, symptomatic patients had a larger decrease in postoperative hemoglobin level (2.66 vs 1.80g/dL, P = .007) and were more likely to undergo blood transfusion, pelvic imaging or reoperation (P < .001). Women with a smaller body mass index and/or higher intraoperative intravenous fluid volume were more likely to have a larger decrease in postoperative hemoglobin level (P < .05). Past surgical history, duration and complexity of the hysterectomy, estimated surgical blood loss, uterine weight, and perioperative use of intravenous ketorolac were not associated with a greater decrease in postoperative hemoglobin (P > .05). Using the University of Pittsburgh Medical Center's annual laparoscopic hysterectomy rate and insurance companies' reimbursement for blood hemoglobin testing, we estimated the national annual cost for hemoglobin testing following total laparoscopic hysterectomy to be $2,804,662. CONCLUSION: Hemoglobin level testing has little clinical benefit following elective total laparoscopic hysterectomy and should be reserved for patients who develop signs or symptoms suggestive of acute anemia. Heath care cost savings can be substantial if this test is no longer routinely requested following total laparoscopic hysterectomies.

Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas.

PURPOSE: The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distinction between LM and LMS. This study addresses the feasibility of applying the two most frequently used approaches for detection of ctDNA: profiling of copy number alterations (CNAs) and point mutations in the plasma of patients with LM. PATIENTS AND METHODS: By shallow whole-genome sequencing, we prospectively examined whether LM-derived ctDNA could be detected in plasma specimens of 12 patients. Plasma levels of lactate dehydrogenase, a marker suggested for the distinction between LM and LMS by prior studies, were also determined. We also profiled 36 LM tumor specimens by exome sequencing to develop a panel for targeted detection of point mutations in ctDNA of patients with LM. RESULTS: We identified tumor-derived CNAs in the plasma DNA of 50% (six of 12) of patients with LM. The lactate dehydrogenase levels did not allow for an accurate distinction between patients with LM and patients with LMS. We identified only two recurrently mutated genes in LM tumors (MED12 and ACLY). CONCLUSION: Our results show that LMs do shed DNA into the circulation, which provides an opportunity for the development of ctDNA-based testing to distinguish LM from LMS. Although we could not design an LM-specific panel for ctDNA profiling, we propose that the detection of CNAs or point mutations in selected tumor suppressor genes in ctDNA may favor a diagnosis of LMS, since these genes are not affected in LM.