Detection of endometrial cancer using tampon-based collection and methylated DNA markers.

OBJECTIVE: Alterations in DNA methylation are early events in endometrial cancer (EC) development and may have utility in EC detection via tampon-collected vaginal fluid. METHODS: For discovery, DNA from frozen EC, benign endometrium (BE), and benign cervicovaginal (BCV) tissues underwent reduced representation bisulfite sequencing (RRBS) to identify differentially methylated regions (DMRs). Candidate DMRs were selected based on receiver operating characteristic (ROC) discrimination, methylation level fold-change between cancers and controls, and absence of background CpG methylation. Methylated DNA marker (MDM) validation was performed using qMSP on DNA from independent EC and BE FFPE tissue sets. Women ≥45 years of age with abnormal uterine bleeding (AUB) or postmenopausal bleeding (PMB) or any age with biopsy-proven EC self-collected vaginal fluid using a tampon prior to clinically indicated endometrial sampling or hysterectomy. Vaginal fluid DNA was assayed by qMSP for EC-associated MDMs. Random forest modeling analysis was performed to generate predictive probability of underlying disease; results were 500-fold in-silico cross-validated. RESULTS: Thirty-three candidate MDMs met performance criteria in tissue. For the tampon pilot, 100 EC cases were frequency matched by menopausal status and tampon collection date to 92 BE controls. A 28-MDM panel highly discriminated between EC and BE (96% (95%CI 89-99%) specificity; 76% (66-84%) sensitivity (AUC 0.88). In PBS/EDTA tampon buffer, the panel yielded 96% (95% CI 87-99%) specificity and 82% (70-91%) sensitivity (AUC 0.91). CONCLUSION: Next generation methylome sequencing, stringent filtering criteria, and independent validation yielded excellent candidate MDMs for EC. EC-associated MDMs performed with promisingly high sensitivity and specificity in tampon-collected vaginal fluid; PBS-based tampon buffer with added EDTA improved sensitivity. Larger tampon-based EC MDM testing studies are warranted.

The first reported case of neonatal alloimmune thrombocytopenia due to low-frequency human platelet antigen-6b antibodies in the United Kingdom.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a potentially serious clinical condition caused by maternal alloantibodies directed to human platelet antigens (HPA), inherited from the father and expressed on fetal/neonatal platelets. We report a case of an otherwise well, full term child, with a profound thrombocytopenia (33 x 109/L). There was no bleeding or obvious explanation for the low platelet count. Samples were sent for the investigation of NAIT. METHOD: Serological investigations were performed on maternal serum taken at day (D)+4 and D+78. The platelet immunofluorescence test (PIFT) and monoclonal antibody immobilization of platelet antigens (MAIPA) assays were performed with a panel of HPA typed donor platelets and against paternal platelets in a crossmatch. HPA 1-6, -9 and -15 and HLA genotyping was performed by in-house PCR-sequence based typing (SBT) and next generation sequencing (NGS). RESULTS: HPA antibody screening of D+4 maternal serum indicated that platelet-specific antibodies were absent. HPA genotyping of the father and child revealed the presence of the low frequency HPA antigen (LFHPA), HPA-6b, which was absent in the mother. Maternal samples were crossmatched against paternal platelets and were positive by PIFT and glycoprotein (GP) IIb/IIIa and HLA class I in the MAIPA assay. The infant required no platelet transfusion support as the thrombocytopenia resolved spontaneously. DISCUSSION: We conclude that the positive crossmatch reaction was due to anti-HPA-6b alloantibodies. This case further emphasizes the importance of platelet crossmatching and HPA genotyping of LFHPA in cases where there is a high clinical suspicion of NAIT but initial screening is negative.

Quantifying procedural pain associated with office gynecologic tract sampling methods.

OBJECTIVE: Emerging technologies may enable detection of endometrial cancer with methods that are less invasive than standard biopsy methods. This study compares patient pain scores among 3 office gynecologic tract sampling methods and explores their potential determinants. METHODS: A prospective study including 3 sampling methods (tampon, Tao brush (TB), endometrial biopsy (EB)) was conducted between December 2015 and August 2017 and included women ≥45 years of age presenting with abnormal uterine bleeding, postmenopausal bleeding, or thickened endometrial stripe. Patients rated pain after each sampling procedure using a 100-point visual analog scale (VAS). RESULTS: Of 428 enrolled, 190 (44.39%) patients underwent all 3 sampling methods and reported a VAS score for each. Nearly half were postmenopausal (n = 93, 48.9%); the majority were parous (172, 90.5%) of which 87.8% had at least one vaginal delivery. Among the 190 patients, the median (IQR) pain score was significantly lower for sampling via tampon (0 [0,2]) compared to TB (28 [12, 52]) or EB (32 [15, 60]) (both p < 0.001, Wilcoxon signed rank test). Among women who underwent tampon sampling, age and pain scores showed a weak positive correlation (Spearman rank correlation, r = 0.14; p = 0.006); EB sampling was associated with a weak inverse correlation between parity and pain scores (r = -0.14; p = 0.016). CONCLUSION: Gynecologic tract sampling using a tampon had significantly lower pain than both EB and TB. Pain with tampon sampling was positively correlated with age and pain with EB sampling was inversely correlated with parity. Pain scores for TB and EB were not significantly related to age, menopausal status, or BMI.

Passenger lymphocyte thrombocytopenia due to human platelet antigen 3a antibodies: Case report and review of literature.

We report a case of severe acute thrombocytopenia occurring within days after a cadaveric liver transplant, received from a female patient with aplastic anemia who died of intracranial bleeding. The donor, who was homozygous for the ITGA2B*002 (HPA-3b) gene, had developed human platelet antigen (HPA)-3a antibodies, whereas the recipient was homozygous for the ITGA2B*001 (HPA-3a) gene. Thrombocytopenia responded to an infusion of immunoglobulin G. This is the first report of a passenger lymphocyte syndrome manifesting with thrombocytopenia due to anti-HPA-3a. We review the literature on thrombocytopenia in the setting of PLS and discuss the differential diagnosis.

A prospective clinical cohort study of women at increased risk for endometrial cancer.

OBJECTIVE: To evaluate endometrial cancer (EC) risk assessment and early detection strategies in high-risk populations, we designed a large, prospective cohort study of women undergoing endometrial evaluation to assess risk factors and collect novel biospecimens for future testing of emerging EC biomarkers. Here we report on the baseline findings of this study. METHODS: Women aged ≥45 years were enrolled at the Mayo Clinic from February 2013-June 2018. Risk factors included age, body mass index (BMI), smoking, oral contraceptive and hormone therapy use, and parity. We collected vaginal tampons, endometrial biopsies, and Tao brush samples. We estimated mutually-adjusted odds ratios (OR) and 95% confidence intervals (CI) using multinomial logistic regression; outcomes included EC, atypical hyperplasia, hyperplasia without atypia, disordered proliferative endometrium, and polyps, versus normal endometrium. RESULTS: Subjects included 1205 women with a mean age of 55 years; 55% were postmenopausal, and 90% had abnormal uterine bleeding. The prevalence of EC was 4.1% (n = 49), predominantly diagnosed in postmenopausal women (85.7%). Tampons and Tao brushings were obtained from 99% and 68% of women, respectively. Age (OR 1.14, 95% CI 1.1-1.2) and BMI (OR 1.39, 95% CI 1.1-1.7) were positively associated with EC; atypical hyperplasia (OR 1.07, 95% CI 1.0-1.1; OR 2.00, 95% CI 1.5-2.6, respectively), and polyps (OR 1.06, 95% CI 1.0-1.1; OR 1.17, 95% CI 1.0-1.3, respectively); hormone therapy use and smoking were inversely associated with EC (OR 0.42, 95%, 0.2-0.9; OR 0.43, 95% CI, 0.2-0.9, respectively). Parity and past oral contraception use were not associated with EC. CONCLUSIONS: Well-established EC risk factors may have less discriminatory accuracy in high-risk populations. Future analyses will integrate risk factor assessment with biomarker testing for EC detection.

Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms.

BACKGROUND: Most endometrial cancer cases are preceded by abnormal uterine bleeding, offering a potential opportunity for early detection and cure of endometrial cancer. Although clinical guidelines exist for diagnostic workup of abnormal uterine bleeding, consensus is lacking regarding optimal management for women with abnormal bleeding to diagnose endometrial cancer. OBJECTIVE: We report the baseline data from a prospective clinical cohort study of women referred for endometrial evaluation at the Mayo Clinic, designed to evaluate risk stratification in women at increased risk for endometrial cancer. Here, we introduce a risk-based approach to evaluate diagnostic tests and clinical management algorithms in a population of women with abnormal bleeding undergoing endometrial evaluation at the Mayo Clinic. STUDY DESIGN: A total of 1163 women aged ≥45 years were enrolled from February 2013 to May 2019. We evaluated baseline absolute risks and 95% confidence intervals of endometrial cancer and endometrial intraepithelial neoplasia according to clinical algorithms for diagnostic workup of women with postmenopausal bleeding (assessment of initial vs recurrent bleeding episode and endometrial thickness measured through transvaginal ultrasound). We also evaluated risks among women with postmenopausal bleeding according to baseline age (<60 vs 60+ years) as an alternative example. For this approach, biopsy would be conducted for all women aged 60+ years and those aged <60 years with an endometrial thickness of >4 mm. We assessed the clinical efficiency of each strategy by estimating the percentage of women who would be referred for endometrial biopsy, the percentage of cases detected and missed, and the ratio of biopsies per case detected. RESULTS: Among the 593 women with postmenopausal bleeding, 18 (3.0%) had endometrial intraepithelial neoplasia, and 47 (7.9%) had endometrial cancer, and among the 570 premenopausal women with abnormal bleeding, 8 (1.4%) had endometrial intraepithelial neoplasia, and 7 (1.2%) had endometrial cancer. Maximum risk was noted in women aged 60+ years (17.7%; 13.0%-22.3%), followed by those with recurrent bleeding (14.7%; 11.0%-18.3%). Among women with an initial bleeding episode for whom transvaginal ultrasound was recommended, endometrial thickness did not provide meaningful risk stratification: risks of endometrial cancer and endometrial intraepithelial neoplasia were nearly identical in women with an endometrial thickness of >4 mm (5.8%; 1.3%-10.3%) and ≤4 mm (3.6%; 0.9%-8.6%). In contrast, among those aged <60 years with an endometrial thickness of >4 mm, the risk of endometrial cancer and endometrial intraepithelial neoplasia was 8.4% (4.3%-12.5%), and in those with an endometrial thickness of ≤4 mm, the risk was 0% (0.0%-3.0%; P=.01). The most efficient strategy was to perform biopsy in all women aged 60+ years and among those aged <60 years with an endometrial thickness of >4 mm, with the lowest percentage referred to biopsy while still detecting all cases. CONCLUSION: Existing clinical recommendations for endometrial cancer detection in women with abnormal bleeding are not consistent with the underlying risk. Endometrial cancer risk factors such as age can provide important risk stratification compared with the assessment of recurrent bleeding. Future research will include a formal assessment of clinical and epidemiologic risk prediction models in our study population as well as validation of our findings in other populations.

A Double-Blind, Placebo-Controlled, Pilot Study of Riluzole Monotherapy for Acute Bipolar Depression.

BACKGROUND: Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of riluzole monotherapy for the treatment of BDep. Nineteen subjects aged 18 to 70 years with bipolar disorder currently experiencing a depressive episode were tapered off of excluded medications and randomized to receive riluzole (50-200 mg/d) or placebo for 8 weeks. Rating scale scores (Montgomery-Åsberg Depression Rating Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Young Mania Rating Scale) were obtained weekly. RESULTS: No significant differences in depressive symptoms were observed between subjects treated with riluzole and those receiving placebo (P = 0.12). Anxiety scores were significantly lower in the placebo group (P = 0.046). An interim analysis was conducted that resulted in stopping the study because of futility; no subjects had achieved treatment response. CONCLUSIONS: Although we found no change in severity of depressive symptoms in BDep patients receiving riluzole compared with placebo, this trial was limited by the relatively high number of subject withdrawals and the small sample size. Thus, while riluzole monotherapy did not demonstrate efficacy for BDep, further studies examining riluzole as adjunctive therapy for this disorder may be warranted.Clinical Trials Identifier NCT00054704.

Human platelet antigen (HPA)-specific immunoglobulin M antibodies in neonatal alloimmune thrombocytopenia can inhibit the binding of HPA-specific immunoglobulin G antibodies.

BACKGROUND: A term baby with unexplained thrombocytopenia and a platelet (PLT) count of 14 × 109 /L (maternal PLT count was 200 × 109 /L) was investigated for neonatal alloimmune thrombocytopenia. STUDY DESIGN AND METHODS: Serologic investigations were performed using the PLT immunofluorescence test (PIFT), monoclonal antibody immobilization of PLT antigens (MAIPA), and a bead-based assay (BBA) with maternal sera taken up to 56 days postdelivery. One serum sample was also separated into "immunoglobulin (Ig)M-rich" and "IgM-depleted" fractions and tested for PLT-specific antibodies. The family was genotyped for HPA. RESULTS: HPA-3a-specific IgM antibodies were detected in the PIFT and confirmed in the BBA. PLT-specific IgG HPA-3a antibodies were not detected in the MAIPA assay and BBA in the initial sample but were detected in both techniques in subsequent serum samples. Testing of IgM-rich and IgM-depleted fractions in the MAIPA assay revealed that IgG antibody binding of the IgM-depleted fraction was inhibited by approximately 50% when it was reconstituted with the IgM-rich fraction suggesting that the IgM antibodies blocked the binding of the IgG antibodies. This effect was not observed when the IgM-depleted fraction or untreated serum was diluted with elution buffer. Incompatibility for HPA-3 was identified between the mother and the infant. The infant received one HPA-1a, -5b negative neonatal PLT transfusion, and one random PLT transfusion, with satisfactory outcomes. Both units were later found to be HPA-3b3b. CONCLUSION: HPA-3a IgM antibodies can inhibit PLT-specific HPA-3a IgG antibodies in the MAIPA assay.

Clinical Manifestations and Outcomes in Surgically Managed Gartner Duct Cysts.

STUDY OBJECTIVE: Gartner duct cysts (GDCs) are rare embryological remnants of the mesonephric duct with the majority of cases discovered incidentally in asymptomatic patients. The largest prior published series evaluating the surgical management of GDCs included 4 patients. The present study aimed to determine the manifestations and outcomes of surgically managed patients with GDCs with important implications for surveillance, monitoring, and management. DESIGN: A retrospective chart review (Canadian Task Force classification III). SETTING: A tertiary care center. PATIENTS: All women diagnosed with GDCs from January 1994 to April 2014 at our institution were identified. Patients were included if they underwent surgical management and had GDCs confirmed by pathology. One hundred twenty-four charts were manually reviewed, and 29 patients were included in the analysis. INTERVENTIONS: All patients underwent surgical management, which included vaginal excision or marsupialization. MEASUREMENTS AND MAIN RESULTS: A total of 29 patients met the inclusion criteria for this study. The median age of the patients included in the analysis was 36 years old. Eleven patients were asymptomatic at the time of diagnosis (37.9%). The reason for surgical intervention was not available in 9 of these patients. Surgical intervention was performed in 2 of the 11 asymptomatic patients because of an increasing size of the lesion during observation. Presenting symptoms included dyspareunia or pain with tampon placement (37.9%), pelvic pain or pressure (24.1%), pelvic mass or bulge (17.2%), and urinary incontinence (6.9%). Preoperative imaging studies were obtained in 62% of patients; ultrasound was used in 44.4%, computed tomographic scanning in 22.2%, magnetic resonance imaging in 16.7%, and multiple modalities in 16.7%. Approximately 10% were found to have other genitourinary anomalies, including a bladder cyst, urethral diverticulum, and a solitary right kidney with uterine didelphis and septate vagina. The average cyst size was 3.5 cm (±1.8 cm). Surgical excision of GDCs was performed in all except for 3 cases of marsupialization. No intraoperative complications occurred. The median follow-up was 82 months (range, 0-246 months). One patient had possible recurrence with dyspareunia and protruding tissue diagnosed 14 months postoperatively. There were no other postoperative complications in the follow-up period. CONCLUSION: GDCs are rare pelvic masses that are often asymptomatic but may present with dyspareunia, pelvic pain or pressure, pelvic mass or bulge, or urinary symptoms. Excision or marsupialization is successful in the majority of cases without significant morbidity.

Risk Factors, Clinical Presentation, and Outcomes for Abdominal Wall Endometriosis.

STUDY OBJECTIVE: To evaluate the risk factors, presentation, and outcomes in cases of abdominal wall endometriosis. DESIGN: A case-control study (Canadian Task Force classification II-2). SETTING: An academic medical center. PATIENTS: A total of 102 (34 cases and 68 controls) were included. INTERVENTIONS: Surgical resection of abdominal wall endometriosis. MEASUREMENTS AND MAIN RESULTS: Cases underwent surgical excision for abdominal wall endometriosis at Mayo Clinic from January 1, 2000, through December 31, 2013. For each case, 2 controls were randomly selected from a list of women who had surgery in the same year with minimal (American Society for Reproductive Medicine stage I-II) endometriosis. A chart review was completed for variables of interest. Regression models were used to identify independent risk factors associated with abdominal wall endometriosis. RESULTS: In 14 years, 2539 women had surgery for endometriosis at Mayo Clinic. Of these, only 34 (1.34%) had abdominal wall endometriosis. The mean age was 35.2 ± 5.9 years, and the median parity was 2 (range, 0-5). Clinical examination diagnosed abdominal wall endometriosis in 41% of cases, with the cesarean delivery scar being the most common site (59%). There was a strong correlation between the size of the lesion on clinical examination compared with the size of the pathology specimen (r2 = 0.74, p < .001). When compared with controls, cases had significantly higher parity and body mass index, more cyclic localized abdominal pain, less dysmenorrhea, longer duration from the start of symptoms to surgery, and more gynecologic surgeries for symptoms without cure. In the final multivariable model, cyclic localized abdominal pain, absence of dysmenorrhea, and previous laparotomy were independently associated with abdominal wall endometriosis with adjusted odds ratios of 10.6 (95% CI 1.85-104.4, p < .001), 12.4 (95% CI 1.64-147.1, p < .001), and 70.1 (95% CI 14.8-597.7, p < .001), respectively, with an area under the curve for the receiver operating characteristic of 0.94 (95% CI, 0.87-0.98). After excision of the disease, repeat surgery was needed in 2 (5.9%) patients with a median time to recurrence of 50.5 (range, 36-65) months. CONCLUSIONS: Abdominal wall endometriosis is a rare but unique form of endometriosis. Careful history and clinical examination can provide accurate diagnosis and avoid unnecessary delay before surgical intervention. Localized cyclic abdominal pain with the absence of dysmenorrhea and a history of prior laparotomy are independent risk factors with very high accuracy for diagnosis.

The interpretation of static positional nystagmus in a balance clinic.

OBJECTIVE: To review the current criteria for the interpretation of positional nystagmus (PN). DESIGN: Videonystagmography data on PN was collected for 90 patients presenting for balance testing with a history of vertigo or imbalance (excluding those diagnosed with benign paroxysmal positional vertigo). These were compared to normative data from 90 asymptomatic subjects. A literature review was carried out regarding threshold criteria for clinically significant PN. These were evaluated using the data collected. STUDY SAMPLE: Clinic group: 90 patients; 37 male, 53 female. Age range 15-82 years. Normative group: Ninety subjects; 31 male, 59 female. Age range 21-79 years. RESULTS: PN was seen in 75.6% of the clinic group and in 50% of the normative group. The prevalence of nystagmus of slow phase velocity (SPV) > 3°/s was significantly higher in the clinic group than the normative group. The maximum SPV recorded in each position was greater from the clinic group than the normative group. CONCLUSIONS: This study supports the use of normative thresholds for SPV for both horizontal and vertical PN. A normative threshold of >3°/s for horizontal and >7°/s for vertical nystagmus is proposed.

Loop Electrosurgical Excision Procedure Instead of Cold-Knife Conization for Cervical Intraepithelial Neoplasia in Women With Unsatisfactory Colposcopic Examinations: A Systematic Review and Meta-Analysis.

OBJECTIVES: This meta-analysis compared loop electrosurgical excision procedure (LEEP) with cold-knife conization (CKC) for treating cervical intraepithelial neoplasia (CIN) in patients with unsatisfactory colposcopic examinations. MATERIAL AND METHODS: A literature search on MEDLINE, EMBASE, Cochrane Systematic Reviews, CENTRAL, Web of Science, and Scopus databases was conducted from inception until April 2015. We included clinical trials and cohort studies comparing CKC with LEEP for treating CIN. The primary outcome was a combined end point of persistent CIN (<6 months after conization) and recurrent CIN (>6 months). Secondary outcomes included procedural, pathologic, and long-term outcomes. Pooled relative risk (RR) and weighted mean difference (WMD) were used to report binary and continuous outcomes, respectively. RESULTS: Among 26 studies, the incidence of persistent and recurrent disease after LEEP was comparable with that after CKC (15.6% vs 7.38%; RR = 1.35; 95% CI = 1.00-1.81). Loop electrosurgical excision procedure was faster, caused less intraoperative bleeding, and resulted in shorter hospital stay (WMD, 9.5 minutes [95% CI = 6.4-12.6 minutes]; WMD, 42.4 mL [95% CI = 21.3-106 mL]; and WMD, 1.5 days [95% CI = 1.1-1.8 days], respectively). Loop electrosurgical excision procedure cones were shallower with overall less volume and weight than CKC (WMD, 5.1 mm [95% CI = 3.2-7.1 mm]; 2.6 mm [95% CI = 0.6-5.7 mm]; and 2.6 g [95% CI = 1.4-3.7 g], respectively). During follow-up, LEEP was associated with less cervical stenosis and fewer unsatisfactory examinations; however, this was not statistically significant (RR, 0.5 [95% CI = 0.1-1.5]; RR, 0.7 [95% CI = 0.4-1.2], respectively). CONCLUSIONS: Loop electrosurgical excision procedure is an acceptable alternative to CKC in women with CIN and unsatisfactory colposcopic examinations. Close follow-up is necessary for prompt detection and treatment of persistent or recurrent disease.

Intraoperative Predictors of Long-term Outcomes After Radiofrequency Endometrial Ablation.

STUDY OBJECTIVE: To identify intraoperative predictors of radiofrequency ablation (RFA) failure after adjusting for clinical risk factors. DESIGN: A cohort study (Canadian Task Force II-2). SETTING: An academic institution in the Upper Midwest. PATIENTS: Data were retrospectively collected from medical records of women who underwent RFA and who had a postprocedure gynecologic assessment between April 1998 and December 2011. INTERVENTIONS: RFA. MEASUREMENTS AND MAIN RESULTS: The primary outcome was RFA failure, which was defined as hysterectomy, repeat ablation, synechiolysis, or treatment with gonadotropin-releasing hormone analogue for postablation pain or bleeding. Cox proportional hazards regression was used to test the predictability of intraoperative variables on RFA failure with adjustment for baseline predictors. We created an RFA index to capture the procedure duration divided by the uterine surface area. One thousand one hundred seventy-eight women were eligible. The median age at ablation was 44 years (interquartile range, 40-48 years), and the median parity was 2 (interquartile range, 2-3). Dysmenorrhea and prior tubal ligation were reported in 37.1% and 37.2% of women, respectively. After adjustment for baseline characteristics, intraoperative predictors of failure were uterine sounding length >10.5 cm (adjusted hazard ratio [HR] = 2.58; 95% confidence interval [CI], 1.31-5.05), uterine cavity length >6 cm (adjusted HR = 2.06; 95% CI, 1.30-3.27), uterine width >4.5 cm (adjusted HR = 2.06; 95% CI, 1.29-3.28), surface area >25 cm(2) (adjusted HR = 2.02; 95% CI, 1.26-3.23), procedure time <93 seconds (adjusted HR = 2.61; 95% CI, 1.25-5.47), and RFA index <3.6 (adjusted HR = 3.14; 95% CI, 1.70-5.77). CONCLUSION: Intraoperative parameters are predictive of long-term adverse outcomes of RFA independent of patient clinical characteristics. Uterine length, procedure duration, and RFA index are associated with unfavorable outcomes and thus could be used to optimize postprocedure patient counseling.

Hysteroscopic Morcellation Versus Resection for the Treatment of Uterine Cavitary Lesions: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis compares hysteroscopic morcellation with electrosurgical resection to treat uterine cavitary lesions. A search of Ovid MEDLINE, Ovid Embase, Scopus, and Web of Science was conducted through August 18, 2015, for randomized controlled trials (RCTs) and prospective and retrospective studies, regardless of surgical indication and study language or sample size. Seven studies were eventually included (4 RCTs and 3 retrospective observational studies), enrolling 650 women. The meta-analysis showed that the total procedure time was significantly shorter for morcellation than for resection (weighted mean difference = 9.36 minutes; 95% confidence interval [CI], -15.08 to -3.64). When reviewing RCTs only, intrauterine morcellation was associated with a smaller fluid deficit and lower odds of incomplete lesion removal. This difference was not statistically significant in observational studies. There was no significant difference in the odds of surgical complications (odds ratio = 0.72; 95% CI, 0.20-2.57) or the number of insertions (weighted mean difference = -3.04; 95% CI, -7.86-1.78). In conclusion, compared with hysteroscopic resection, hysteroscopic morcellation is associated with a shorter operative time and possibly lower odds of incomplete lesion removal. The certainty in evidence was limited by heterogeneity and the small sample size.

Endometrial Ablation in Women With Abnormal Uterine Bleeding Related to Ovulatory Dysfunction: A Cohort Study.

STUDY OBJECTIVE: To evaluate the efficacy and safety of endometrial ablation (EA) for the treatment of abnormal uterine bleeding (AUB) associated with ovulatory dysfunction. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic medical center. PATIENTS: Women with AUB who underwent EA during an 8-year period. INTERVENTIONS: EA by radiofrequency or thermal balloon ablation techniques. MEASUREMENTS AND MAIN RESULTS: Women with AUB were divided into 2 groups: irregular bleeding with ovulatory dysfunction (AUB-O) or regular heavy bleeding related to a primary endometrial disorder (AUB-E). Outcome measures included rates of amenorrhea and treatment failure (ie, need for reablation or hysterectomy). Outcomes were compared between groups using survival analyses and chi-square tests. Known confounders were adjusted for using Cox and logistic regression models. Five-year cumulative treatment failure rates were 11.7% (95% confidence interval [CI], 6.5%-16.9%) for AUB-O and 12.3% (95% CI, 8.4%-16.2%) for AUB-E (p = .62). The unadjusted hazard ratio for treatment failure was 0.87 (95% CI, 0.72-1.05, p = .16). After adjusting for known risk factors for failure, the hazard ratio was 1.48 (95% CI, 0.82-2.65, p = .19). The rates of amenorrhea were 11.8% for AUB-O and 13.8% for AUB-E with an unadjusted odds ratio of 0.84 (95% CI, 0.48-1.48, p = .55). After adjusting for factors for amenorrhea after EA, the odds ratio was 1.08 (95% CI, 0.62-1.84, p =.78). No pregnancies or endometrial cancers occurred after EA. CONCLUSION: EA is effective in women with AUB-O and can be used as an alternative to hysterectomy or in patients with contraindications to medical management of AUB-O.

Combined Endometrial Ablation and Levonorgestrel Intrauterine System Use in Women With Dysmenorrhea and Heavy Menstrual Bleeding: Novel Approach for Challenging Cases.

STUDY OBJECTIVE: To evaluate the feasibility and impact of levonorgestrel intrauterine system (LNG-IUS) on treatment failure after endometrial ablation (EA) in women with heavy menstrual bleeding (HMB) and dysmenorrhea at 4 years. DESIGN: Cohort study (Canadian Task Force II-2). SETTING: An academic institution in the upper Midwest. PATIENTS: All women with HMB and dysmenorrhea who underwent EA with combined placement of LNG-IUS (EA/LNG-IUS cohort, 23 women) after 2005 and an historic reference group from women who had EA alone (EA cohort, 65 women) from 1998 through the end of 2005. INTERVENTION: Radiofrequency EA, thermal balloon ablation, and LNG-IUS. MEASUREMENTS AND MAIN RESULTS: The primary outcome was treatment failure defined as persistent pain, bleeding, and hysterectomy after EA at 4 years. The combined treatment failure outcome was documented in 2 patients (8.7%) in the EA/LNG-IUS group and 19 patients (29.2%) in the EA group with an unadjusted OR of .23 (95% CI, .05-1.08). After adjusting for known risk factors of failure, the adjusted OR was .19 (95% CI, .26-.88). None of the women who underwent EA/LNG-IUS had hysterectomy for treatment failure compared with 16 (24%) in the EA group (p = .009); postablation pelvic pain was documented in 1 woman (4.3%) in the EA/LNG-IUS group compared with 8 women (12.3%) in the EA group (p = .24). One woman in the EA/LNG-IUS group (4.3%) presented with persistent bleeding compared with 15 (23.1%) in the EA group (p = .059). Office removal of the intrauterine device was performed in 4 women with no complications. CONCLUSION: LNG-IUS insertion at the time of EA is feasible and can provide added benefit after EA in women with dysmenorrhea and HMB.

Asymptomatic thickened endometrium in postmenopausal women: malignancy risk.

STUDY OBJECTIVE: To assess the diagnostic findings and determine the frequency of malignancy in postmenopausal women evaluated by office hysteroscopy for a thickened endometrium without bleeding. DESIGN: Retrospective cohort (Canadian Task Force classification II-B). SETTING: Academic medical center in the Midwestern United States. PATIENTS: Over 3600 women underwent an office hysteroscopy between January 1, 2007, and October 20, 2011, for abnormal uterine bleeding or an abnormal ultrasound. Of these, 154 postmenopausal women had a thickened endometrium (>4 mm) and no bleeding. INTERVENTIONS: Flexible office hysteroscopy using a 3.1-mm scope with saline as the distending media was performed for clinical reasons, and results were captured within a research database. MEASUREMENTS AND MAIN RESULTS: For the 154 women, the range of endometrial measurements was 4.2 to 28 mm (mean = 10.0 mm). Hysteroscopy diagnoses included 93 patients with polyps, 19 with myomas or uterine synechiae, and 34 with benign-appearing endometrium. Nine hysteroscopies were inadequate because of poor visualization (n = 1), cervical stenosis (n = 6), or patient discomfort (n = 2). Endometrial biopsies (EMBs) were performed in 109 patients, and none were found to have cancer or an atypical endometrium. Six had simple hyperplasia without atypia, and their endometrial measurements were within the range of the patients in our study who had a benign endometrium (5-15 mm, mean = 10.3). Of the women with a polyp, 73 (78.4%) subsequently underwent polypectomy. On final pathology, 1 had cancer (endometrial measurement = 24 mm), and 1 had complex hyperplasia with atypia (endometrial measurement = 17 mm). EMBs performed in the office for these 2 patients showed an insufficient endometrium and inactive endometrium, respectively. CONCLUSION: Cancer and atypia can occur in asymptomatic women. Endometrial thickness was 17 mm or greater in 2 cases, and EMBs performed in the office were inconsistent with the final diagnosis. Hysteroscopy is important when ultrasound and EMB do not agree. Polypectomy may be indicated even in asymptomatic women, but further studies regarding an endometrial measurement threshold or polyp size are warranted.