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.

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.

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.

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.

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.

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.

Long-term outcomes after intrauterine morcellation vs hysteroscopic resection of endometrial polyps.

STUDY OBJECTIVE: To compare the long-term outcomes of intrauterine morcellation (IUM) of endometrial polyps vs a traditional operative polypectomy technique, hysteroscopic resection (HSR), and to identify factors predictive of recurrent abnormal uterine bleeding (AUB) after operative polypectomy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Minimally invasive gynecologic surgery practice in a tertiary care center. PATIENTS: Women who underwent operative hysteroscopic polypectomy between January 1, 2004 and December 31, 2009. INTERVENTIONS: Intrauterine morcellation or HSR with evaluation and/or treatment of recurrent AUB after operative polypectomy. MEASUREMENTS AND MAIN RESULTS: Of 311 patients (IUM group, 139; HSR group, 172), 167 (53.7%) had at least 1 gynecologic follow-up visit and 57 (18.4%) had recurrent AUB. Subsequent gynecologic clinic visit rates were similar between the 2 groups (HSR, 58.1%, vs IUM, 48.2%; p = .08). Recurrence of AUB within the first 4 years of follow-up was similar between the IUM and HSR groups (hazard ratio for HSR vs IUM, 1.12; 95% confidence interval, 0.64-1.98; p = .59). However, recurrence of endometrial polyps approached statistical significance (hazard ratio, 3.3; 95% confidence interval, 0.94-11.49; p = .06). Premenopausal status, history of hormone replacement therapy, multiparity, and polycystic ovarian syndrome were independently associated with AUB recurrence. There were no reports of inability to establish a histopathologic diagnosis among all pathology specimens evaluated. CONCLUSION: Compared with HSR, intrauterine morcellation may be associated with lower recurrence of endometrial polyps. However, the incidence of recurrent AUB is independent of polypectomy method.

Nonresectoscopic endometrial ablation in high-risk surgical patients: a cohort study.

STUDY OBJECTIVE: To evaluate the use of nonresectoscopic endometrial ablation in women with high anesthetic and surgical risk compared with low-risk women based on the American Society of Anesthesia (ASA) physical status stratification. DESIGN: This is a cohort study of women who were classified as high-risk (HR) or low-risk (LR) cohorts based on ASA physical status stratification. The ASA classification includes 6 grades: ASAP1, a normal healthy person; ASAP2, mild systemic disease; ASAP3, severe systemic disease; ASAP4, severe systemic disease that is a constant threat to life; ASAP5, a critically ill patient who is not expected to survive without the operation; and ASAP6, declared brain-dead patient whose organs are being removed for donor purposes. Baseline characteristics including comorbidities were obtained. Outcome measures included amenorrhea, treatment failure, and operative complications. The time to treatment failure was compared using Kaplan-Meier analysis. Risk adjustments were performed using regression models. SETTING: Academic medical center in the Upper Midwest. PATIENTS: Seven-hundred eleven women underwent nonresectoscopic endometrial ablation at our institution between January 1998 and December 2005. INTERVENTIONS: Bipolar radiofrequency was used in 448 women and thermal balloon ablation in 263 women. MEASUREMENTS AND MAIN RESULTS: The HR cohort had a higher proportion of women with cardiac disease (27.1% vs. 6.7%, p < .001) and more women with nongynecologic cancer (12.3% vs. 2.9%, Fisher exact test, p < .001). Nonetheless, endometrial ablation had comparable efficacy in both the HR and LR cohorts with 5-year failure rates of 11.7% and 14.8% (p = .659), respectively. Amenorrhea rates were also similar in both cohorts (29.7% vs. 27.2%, p = .645). After adjusting for known confounders including age, parity, dysmenorrhea, previous tubal ligation, uterine length, and the type of the procedure, the calculated hazard ratio for failure in the HR cohort was 0.80 (95% confidence interval; 0.31-1.74, p = .607), and the adjusted odds ratio for amenorrhea was 1.27 (95% confidence interval, 0.71-2.20; p = .411). Complications were rare in both groups. The mortality rate in the HR cohort was significantly higher compared with the LR cohort (7.9% vs. <1%, p < .001), but this was not related to the ablation procedures. CONCLUSION: For women who are high anesthetic and surgical risks because of serious underlying comorbidities, nonresectoscopic endometrial ablation can provide minimally invasive, safe, and effective therapy for menorrhagia.

Laparoscopic appendectomy in women without identifiable pathology undergoing laparoscopy for chronic pelvic pain.

OBJECTIVES: To assess the effectiveness of appendectomy in women undergoing laparoscopy for chronic pelvic pain without identifiable pathology. METHODS: This retrospective cohort study included women aged 15 to 50 years who underwent laparoscopic surgery for chronic pelvic pain without identifiable pathology. The cohort was divided into 2 groups: women who underwent appendectomy and women who had not undergone appendectomy at laparoscopic surgery. Postoperative pain was assessed at 6-week follow-up and by subsequent mailed questionnaire. RESULTS: Women who underwent appendectomy (n = 19) were significantly more likely to report improvement in pain at 6-week follow-up than women who did not undergo appendectomy (n = 76) (93% vs 16%; P < .001). Thirty-six patients (38%) responded to the questionnaire at a median of 4.2 years after surgery, when the median change (improvement) in reported pain was greater in the appendectomy group than in the nonappendectomy group. CONCLUSION: Appendectomy is effective therapy for patients with chronic pelvic pain of unknown etiology who are undergoing laparoscopy.

Direct aspiration endometrial biopsy via flexible hysteroscopy.

STUDY OBJECTIVE: To determine feasibility and efficacy of direct aspiration endometrial biopsy via the fluid channel of a flexible diagnostic hysteroscope. DESIGN: Retrospective review (Canadian Task Force classification II-3). SETTING: Abnormal uterine bleeding clinic in a tertiary care center. PATIENTS: All women who underwent direct aspiration endometrial biopsy from January 2007 through August 2011 via a flexible diagnostic hysteroscope because traditional office-based endometrial biopsy using a suction piston device was not technically possible. INTERVENTIONS: Diagnostic hysteroscopy followed by direct aspiration endometrial biopsy, accomplished by applying suction to the fluid channel of a 3.1-mm flexible diagnostic hysteroscope via a 10-mL syringe. The hysteroscope tip was agitated within the uterine cavity to obtain a tissue sample. MEASUREMENTS AND MAIN RESULTS: The median age of the 32 identified patients was 50 years; 18 women (56%) were nulliparous, and 10 (31%) were postmenopausal. Thirty-one patients underwent hysteroscopy/direct aspiration biopsy because of abnormal uterine bleeding or postmenopausal bleeding. The vaginoscopic approach was used in 19 patients (59%). Indications for direct aspiration endometrial biopsy included cervical stenosis, inability to pass the endometrial biopsy instrument into the uterine cavity, and patient intolerance of endometrial biopsy. Adequate endometrial samples were obtained in 28 patients (87.5%). In 3 of 4 patients in whom direct aspiration endometrial biopsy did not provide sufficient tissue, hysteroscopy revealed an atrophic-appearing endometrium. The direct aspiration endometrial biopsy diagnosis was confirmed in 5 of 7 patients who subsequently underwent dilation and curettage or hysterectomy. CONCLUSION: Direct aspiration endometrial biopsy is a simple and effective endometrial sampling method when traditional office-based endometrial biopsy is not feasible. Further prospective studies including larger populations are needed to confirm these results.

Safety of culdotomy as a surgical approach: implications for natural orifice transluminal endoscopic surgery.

OBJECTIVE: To evaluate the efficacy and safety of culdotomy as a surgical approach to access the peritoneal cavity and discuss its implications for natural orifice transluminal endoscopic surgery (NOTES). METHODS: A retrospective chart review of women undergoing culdotomy for tubal sterilization (N 219) between January 1995 and December 2005 was performed. The Accordion Grading System was used for the severity of complications. RESULTS: No intraoperative complications were noted. Postoperative complications occurred in 7 patients (3.2%): 6 infections (grade 2) and 1 case of hemorrhage (grade 3). Conversion to laparoscopy was necessary in 10 patients (2.2%) due to anatomical constraints or pelvic adhesions; however, culdotomy with entry into the abdominal cavity was nevertheless successful in all 10 cases. The difference in the proportion with a history of pelvic surgery between the conversion and nonconversion groups was not statistically significant (P = .068). Patients with BMI ≥30 had a higher conversion rate compared to patients with BMI <30 (11.4% versus 1.5%, P = .011). Tubal sterilization via culdotomy was successfully performed in all 11 women with no prior vaginal deliveries. CONCLUSION: Culdotomy appears to be a safe surgical approach to access the peritoneal cavity and is associated with a low complication rate. These data support the feasibility and safety of utilizing the cul-de-sac as an access portal for natural orifice transluminal endoscopic surgery.

Efficacy and safety of global endometrial ablation after cesarean delivery: a cohort study.

OBJECTIVE: The objective of the study was to evaluate the efficacy and safety of global endometrial ablation in women with a history of cesarean delivery. STUDY DESIGN: We performed a historical cohort study of patients who underwent endometrial ablation for menorrhagia between 1998 and 2005. Outcome measures included amenorrhea, treatment failure, and operative complications. Time to treatment failure was compared using Kaplan-Meier analysis. Risk adjustments were performed using Cox and logistic regression models. RESULTS: Of 704 patients meeting inclusion criteria, 162 (23%) had a history of 1 or more cesarean deliveries. Women with and without a history of cesarean delivery had comparable rates for 5 year cumulative endometrial ablation failure, amenorrhea, treatment failure, and operative complications. The type of ablation device and number of previous cesarean deliveries did not affect any outcomes. CONCLUSION: The efficacy and safety of endometrial ablation are comparable in women with or without a history of cesarean delivery.

Endometrial cancer after endometrial ablation: systematic review of medical literature.

Data are limited regarding the occurrence of endometrial cancer after endometrial ablation (EA). A systematic review of the English-language medical literature was performed of cases of endometrial cancer after EA. This review included the present case report involving a 47-year-old woman with a diagnosis of stage IA, grade 1 endometrial adenocarcinoma 5 years after radiofrequency EA. The systematic literature review identified 22 endometrial cancer cases occurring after EA. Most (76.5%) were stage I at diagnosis. Time to endometrial cancer diagnosis ranged from 2 weeks to 10 years following EA. All but 3 cases involved patients with known endometrial cancer risk factors. To our knowledge, the present case is the first reported occurrence of endometrial cancer after radiofrequency EA. Endometrial cancer has been detected after EA at variable intervals. Occurrence of endometrial cancer after EA is low, yet it continues to be difficult to quantify through retrospective analyses.