Ultrasonographic evaluation of endometrial stripe thickness is insufficient to rule out uterine serous carcinoma.

PURPOSE: Uterine serous carcinoma (USC) is a rare endometrial cancer representing less than 10% of uterine cancers but contributing to up to 50% of the mortality. Delay in diagnosis with this high-grade histology can have significant clinical impact. USC is known to arise in a background of endometrial atrophy. We investigated endometrial stripe (EMS) thickness in USC to evaluate current guidelines for postmenopausal bleeding in the context of this histology. METHODS: Retrospective chart review was conducted using ICD-9 and ICD-10 codes over an 18-year period. We included 139 patients with USC and compared characteristics of patients with EMS ≤ 4 mm and EMS > 4 mm. Chi-square or Fisher's exact tests were used to compare proportions and two-tailed t-tests to compare means. A p-value of < 0.05 was considered statistically significant. RESULTS: Most patients were white, obese, and multiparous. Thirty-two (23%) had an EMS ≤ 4 mm; 107 (77%) had an EMS > 4 mm. There were no statistically significant differences in age at diagnosis or presenting symptoms between groups, and postmenopausal bleeding was the most common symptom in each group. CONCLUSION: Nearly 25% of patients with USC initially evaluated with transvaginal ultrasound were found to have an EMS ≤ 4 mm. If transvaginal ultrasound is used to triage these patients, one in four women will potentially experience a delay in diagnosis that may impact their prognosis.

Success Rates of Sentinel Lymph Node Mapping for Endometrial Cancer in Patients with Body Mass Index < 45 Compared with Body Mass Index ≥ 45.

STUDY OBJECTIVE: The objective is to evaluate the rate of sentinel lymph node (SLN) mapping in patients with body mass index (BMI [kg/m2]) BMI ≥ 45 compared with < 45. DESIGN: A retrospective chart review. SETTING: Three urban referral-based settings-1 academic and 2 community based. PATIENTS: Patients age ≥ 18 years, with endometrial intraepithelial neoplasia or clinical stage 1 endometrial cancer who underwent robot-assisted total laparoscopic hysterectomy with attempted SLN mapping between January 2015 and December 2021. INTERVENTIONS: Robot-assisted total laparoscopic hysterectomy with attempted SLN mapping. MEASUREMENTS AND MAIN RESULTS: A total of 933 subjects were included: 795 (85.2%) with BMI < 45 and 138 (14.8%) with BMI ≥ 45. Comparing the BMI < 45 with BMI ≥ 45 group, bilateral mapping was successful in 541 (68.1%) vs 63 (45.7%), respectively. Unilateral mapping was successful in 162 (20.4%) vs 33 (23.9%), respectively. Failure to map occurred in 92 (11.6%) vs 42 (30.4%) (p <.001), respectively. Exploratory analysis also suggested an inverse relationship between success rate of bilateral SLN mapping and BMI, with patients with BMI < 20 having bilateral SLN mapping rates of 86.5% and patients with BMI ≥ 61 having rates of 20.0%. The steepest decline in bilateral SLN mapping rates was from BMI group 46 to 50 compared to 51 to 55, at 55.4% to 37.5%, respectively. Adjusted odds ratio (compared with those with BMI < 30) for those in the BMI 30 to 44 group was 0.36 (95% confidence interval 0.21-0.60) and for those in the BMI ≥ 45 group was 0.10 (95% confidence interval 0.06-0.19). CONCLUSION: There is a statistically significant lower rate of SLN mapping in patients with a BMI ≥ 45 than BMI < 45. Understanding the success of SLN mapping in patients with morbid obesity is essential for preoperative counseling, surgical planning, and developing a risk-appropriate postoperative treatment plan.

Ovarian preservation compared to oophorectomy in premenopausal women with early-stage, low-grade endometrial Cancer: A cost-effectiveness analysis.

OBJECTIVES: Standard treatment for endometrial cancer is a hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. In premenopausal women, removal of the ovaries may not be necessary and could increase the risk of all-cause mortality. We sought to estimate the outcomes, costs, and cost-effectiveness of oophorectomy versus ovarian preservation in premenopausal women with early-stage, low-grade endometrial cancer. METHODS: A decision-analytic model was designed using TreeAge software comparing oophorectomy to ovarian preservation in premenopausal women with early-stage, low-grade endometrial cancer. We used a theoretical cohort of 10,600 women to represent our population of interest in the United States in 2021. Outcomes included cancer recurrences, ovarian cancer diagnoses, deaths, rates of vaginal atrophy, costs, and quality-adjusted life years (QALYs). The cost-effectiveness threshold was set at $100,000/QALY. Model inputs were derived from the literature. Sensitivity analyses were conducted to evaluate the robustness of the results. RESULTS: Oophorectomy resulted in more deaths and higher rates of vaginal atrophy, while ovarian preservation resulted in 100 cases of ovarian cancer. Ovarian preservation resulted in lower costs and higher QALYs making it cost effective when compared to oophorectomy. Sensitivity analyses demonstrated the probability of cancer recurrence after ovarian preservation and probability of developing ovarian cancer were the most impactful variables in our model. CONCLUSION: Ovarian preservation is cost-effective in premenopausal women with early-stage, low-grade endometrial cancer when compared to oophorectomy. Ovarian preservation may prevent surgical menopause, which may improve quality of life and overall mortality without compromising oncologic outcomes, and should be strongly considered in premenopausal women with early stage disease.

Adjuvant Human Papillomavirus Vaccination After Excisional Procedure for Cervical Intraepithelial Neoplasia: A Cost-Effectiveness Analysis.

OBJECTIVE: To examine the cost effectiveness of human papillomavirus (HPV) vaccination after excisional procedure compared with no vaccination. METHODS: We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent an excisional procedure followed by nonavalent HPV vaccination to those who underwent an excisional procedure without vaccination. Our theoretical cohort contained 250,000 patients, the approximate number undergoing excisional procedures annually in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), recurrence events, number of surveillance Pap tests with co-testing, number of colposcopies, and second excisional procedures. Probabilities of recurrence were based on a recently published meta-analysis. All values were derived from the literature, and QALYs were discounted at a rate of 3%. Outcomes were applied for 4 years after the initial excisional procedure. Our cost-effectiveness threshold was $100,000 per QALY. Sensitivity analyses were performed to evaluate the robustness of the model. RESULTS: In our theoretical cohort of patients who underwent an excisional procedure, the HPV vaccination strategy was associated with 17,281 fewer recurrences of cervical intraepithelial neoplasia (CIN) (8,360 fewer cases of CIN 1 and 8,921 fewer cases of CIN 2 or 3), 26,203 fewer Pap tests (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second excisional procedures (4,779 vs 13,701). The vaccination strategy was associated with a higher cost of $135 million. Vaccination was a cost-effective strategy, with an incremental cost-effectiveness ratio of $29,181 per QALY, compared with no vaccination. In our sensitivity analyses, the HPV vaccination strategy remained cost effective until the cost of the three-dose HPV vaccine series reached $1,899 or the baseline (nonvaccinated) probability of recurrence was less than 4.8%. CONCLUSION: In our model, HPV vaccination for patients with a prior excisional procedure led to improved outcomes and was cost effective. Our study suggests that clinicians should consider offering the three-dose HPV vaccine series to patients who have undergone an excisional procedure to decrease the risk of CIN recurrence and its sequelae.

Hysterectomy with a general gynecologist vs gynecologic-oncologist in the setting of endometrial intraepithelial neoplasia: a cost-effectiveness analysis.

BACKGROUND: Standard treatment for patients with endometrial intraepithelial neoplasia (EIN) is a hysterectomy, which has a 43% risk of concomitant endometrial cancer on final pathology. General gynecologists and gynecologic-oncologists perform hysterectomies; however, patients who have a hysterectomy for EIN with a general gynecologist and are found to have cancer may require a second surgery by a gynecologic-oncologist to complete staging. There is ongoing discussion regarding whether patients with EIN should be provided the option to receive the initial hysterectomy with a gynecologic-oncologist. OBJECTIVE: This study aimed to better understand if patients with EIN should be initially referred to a gynecologic-oncologist for treatment. We examined the cost-effectiveness of hysterectomy by general gynecologists vs gynecologic-oncologists for patients with EIN. STUDY DESIGN: We created a decision-analytical model using TreeAge Pro software to compare outcomes between hysterectomies by general gynecologists and those by gynecologic-oncologists in patients with EIN. Our theoretical cohort contained 200,000 patients, an estimate of the number of individuals diagnosed with EIN each year in the United States. Outcomes included costs, quality-adjusted life years, primary lymph node dissection, secondary lymph node dissection, surgical site infection, and perioperative mortality. We assumed that surgical morbidity and mortality were the same under generalist and specialist care and applied costs of travel and lost work for those seeing a gynecologic-oncologist. We performed univariable sensitivity analyses and multivariable probabilistic sensitivity analysis to assess the model's robustness given the uncertainty of model inputs. RESULTS: In our theoretical cohort of 200,000 patients with EIN, hysterectomy with a gynecologic-oncologist was associated with a decrease of 10,811 second surgeries for lymph node dissection, 87 surgical site infections, and 9 perioperative mortalities. When hysterectomy was performed by a general gynecologist, 9 fewer patients had a lymph node dissection because of perioperative mortalities that occurred before lymph node dissection with a gynecologic-oncologist. Hysterectomy with a gynecologic-oncologist was the dominant, cost-effective strategy because it saved $116 million and increased quality-adjusted life years by 180. In our univariable analyses, hysterectomy with a gynecologic-oncologist was cost-saving and increased quality-adjusted life years over a wide range of probabilities and costs for lymph node dissection, surgical site infection, and perioperative mortality. However, hysterectomy with a gynecologic-oncologist was only a cost-effective and cost-saving strategy in just over 50% of multivariable simulations, demonstrating that there is significant uncertainty in the model's cost-effectiveness. CONCLUSION: In our model, hysterectomy with a gynecologic-oncologist for patients with EIN was associated with cost savings and increased quality-adjusted life years. Our study supports that patients undergoing hysterectomy for EIN at institutions using Mayo criteria to determine need for lymphadenectomy may benefit from surgery with a gynecologic-oncologist rather than a general gynecologist to reduce costs and adverse events associated with a second surgery.

Does obesity influence the preferred treatment approach for early-stage cervical cancer? A cost-effectiveness analysis.

OBJECTIVE: Abdominal radical hysterectomy in early-stage cervical cancer has higher rates of disease-free and overall survival compared with minimally invasive radical hysterectomy. Abdominal radical hysterectomy may be technically challenging at higher body mass index levels resulting in poorer surgical outcomes. This study sought to examine the influence of body mass index on outcomes and cost effectiveness between different treatments for early-stage cervical cancer. METHODS: A Markov decision-analytic model was designed using TreeAge Pro software to compare the outcomes and costs of primary chemoradiation versus surgery in women with early-stage cervical cancer. The study used a theoretical cohort of 6000 women who were treated with abdominal radical hysterectomy, minimally invasive radical hysterectomy, or primary chemoradiation therapy. We compared the results for three body mass index groups: less than 30 kg/m2, 30-39.9 kg/m2, and 40 kg/m2 or higher. Model inputs were derived from the literature. Outcomes included complications, recurrence, death, costs, and quality-adjusted life years. An incremental cost-effectiveness ratio of less than $100 000 per quality-adjusted life year was used as our willingness-to-pay threshold. Sensitivity analyses were performed broadly to determine the robustness of the results. RESULTS: Comparing abdominal radical hysterectomy with minimally invasive radical hysterectomy, abdominal radical hysterectomy was associated with 526 fewer recurrences and 382 fewer deaths compared with minimally invasive radical hysterectomy; however, abdominal radical hysterectomy resulted in more complications for each body mass index category. When the body mass index was 40 kg/m2 or higher, abdominal radical hysterectomy became the dominant strategy because it led to better outcomes with lower costs than minimally invasive radical hysterectomy. Comparing abdominal radical hysterectomy with primary chemoradiation therapy, recurrence rates were similar, with more deaths associated with surgery across each body mass index category. Chemoradiation therapy became cost effective when the body mass index was 40 kg/m2 or higher. CONCLUSION: When the body mass index is 40 kg/m2 or higher, abdominal radical hysterectomy is cost saving compared with minimally invasive radical hysterectomy and primary chemoradiation is cost effective compared with abdominal radical hysterectomy. Primary chemoradiation may be the optimal management strategy at higher body mass indexes.

Cervical Cancer Screening in Postmenopausal Women: Is It Time to Move Toward Primary High-Risk Human Papillomavirus Screening?

Background: Cervical cytology in postmenopausal women is challenging due to physiologic changes of the hypoestrogenic state. Misinterpretation of an atrophic smear as atypical squamous cells of uncertain significance (ASCUS) is one of the most common errors. We hypothesize that high-risk human papillomavirus (hrHPV) testing may be more accurate with fewer false positive results than co-testing of hrHPV and cervical cytology for predicting clinically significant cervical dysplasia in postmenopausal women. Materials and Methods: We conducted a retrospective analysis of 924 postmenopausal and 543 premenopausal women with cervical Pap smears and hrHPV testing. Index Pap smear diagnoses (ASCUS or greater vs. negative for intraepithelial lesion) and hrHPV testing results were compared with documented 5-year clinical outcomes to evaluate sensitivity and specificity of hrHPV compared with co-testing. Proportions of demographic factors were compared between postmenopausal women who demonstrated hrHPV clearance versus persistence. Results: The prevalence of hrHPV in premenopausal and postmenopausal women was 41.6% and 11.5%, respectively. The specificity of hrHPV testing (89.6% [87.4-91.5]) was significantly greater compared with co-testing (67.4% [64.2-70.4]) (p < 0.05). A greater proportion of women with persistent hrHPV developed cervical intraepithelial lesion 2 or greater (CIN2+) compared with women who cleared hrHPV (p = 0.012). No risk factors for hrHPV persistence in postmenopausal women were identified. Conclusion: Our data suggest that hrHPV testing may be more accurate than co-testing in postmenopausal women and that cytology does not add clinical value in this population. CIN2+ was more common among women with persistent hrHPV than those who cleared hrHPV, but no risk factors for persistence were identified in this study.

Prognostic significance of splenectomy as part of initial cytoreductive surgery in ovarian cancer.

PURPOSE: We sought to examine how splenectomy as part of up-front cytoreductive surgery in ovarian cancer influences the postoperative course and affects survival. METHODS: We reviewed cases of ovarian cancer diagnosed at Massachusetts General Hospital from 1994 to 2008 and found 44 patients who had a splenectomy as part of their up-front cytoreductive surgery. These were compared to 171 patients who did not undergo splenectomy. We evaluated age at diagnosis, estimated blood loss, percentage of patients whose disease was optimally cytoreduced (<1 cm), reason for splenectomy (oncologic vs. surgical), length of stay, time to first chemotherapy treatment, and survival. RESULTS: In the splenectomy cohort, the mean age at diagnosis was 64 (44-83) years. A total of 37 of 44 (84%) patients were optimally cytoreduced. Mean estimated blood loss was 1326 ml. The purpose of splenectomy was to accomplish an optimal cytoreduction (oncologic) in 82% of cases. Median length of stay was 13 (6-76) days. Median time to first chemotherapy was 13.5 (5-54) days. The median disease-free interval and overall survival of the splenectomy cohort were 8 and 30 months, respectively. The median overall survival for patients whose disease was optimally cytoreduced in the splenectomy cohort compared to the no-splenectomy group was 30 and 45 months (P < 0.045), respectively. CONCLUSIONS: The addition of splenectomy to up-front cytoreductive surgery was feasible and safe. However, it appears to carry with it a shortened survival that is unrelated to postoperative morbidity. Our data raise the questions that splenectomy is needed for optimal cytoreduction in more biologically aggressive disease and that splenectomy may be an independent prognostic factor related to depressed immune function.

Mouse models of uterine corpus tumors: clinical significance and utility.

Uterine tumors, whether benign or malignant, are diagnosed in a significant portion of women and are associated with a number of co-morbidities that negatively impact quality of life. Uterine tumors can be derived from the epithelial (endometrial hyperplasia or carcinoma) and mesenchymal (leiomyoma, sarcoma) layers of the uterus. The exact etiologies of the various tumor types are yet to be defined. Collectively their development and progression often results from aberrant steroid hormone exposure or dysregulation of related growth factor signaling and apoptotic pathways, reflecting the role of steroid hormone-dependent signaling and survival pathways in the cycles of cell growth and involution that characterize normal uterine physiology. While molecular analyses of human tumors can identify candidate genetic and epigenetic lesions contributing to uterine tumor initiation and progression, in vivo genetic models are needed to establish the functional significance of such lesions and their contribution to tumorigenesis. For this purpose, genetically-engineered mouse models have proven valuable. Here we review genetically-modified mouse models that develop uterine tumors and compare their pathology, utility/feasibility, and discuss their clinical relevance.

Upregulation of MUC4 in cervical squamous cell carcinoma: pathologic significance.

MUC4 is a transmembrane glycoprotein more highly expressed in cervical dysplasia than benign cervical epithelium. We sought to determine whether MUC4 expression differs between benign and malignant cervical tissue. Fifty-eight patients with benign, dysplastic, or malignant cervical pathology were identified retrospectively, and representative sections were stained with a mouse monoclonal anti-MUC4 antibody. Semiquantitative analysis was performed on benign, dysplastic, and malignant regions by scoring staining intensity (0: negative, 1: weak, 2: moderate, and 3: strong) and distribution (focal <10%, multifocal=10%-60%, diffuse > or =60%). In samples with benign glycogenated squamous epithelium, only the parabasal cells had MUC4 staining, and 48.5% had an intensity of 2 or 3. All samples with immature squamous metaplasia were positive through the entire epithelial thickness. Cervical intraepithelial neoplasia (CIN) 1 samples had variable staining with an intensity similar to glycogenated squamous epithelium but distribution similar to squamous metaplasia. All CIN 3 (n=21) and invasive squamous cell carcinomas (n=17) had increased MUC4 staining intensity (P<0.001 and P<0.001) and increased diffuse staining (P<0.001 and P<0.001) compared with the limited staining in glycogenated squamous epithelium. In contrast, no differences in staining were observed between benign endocervical glands, adenocarcinoma in situ, and invasive adenocarcinoma. These expression patterns suggest that MUC4 is a lineage marker in benign cervical tissue that may have aberrant expression in squamous dysplasia and carcinoma. Further studies may elucidate the role of MUC4 in the development of squamous cell cervical cancer.

Incarcerated vaginal herniation of the omentum mimicking vaginal prolapse.

We present a 33-year-old woman with a history of radical hysterectomy and pelvic radiation who developed a nonreducible high anterior vaginal wall bulge, postoperative pelvic pain, and dyspareunia. Dynamic MRI revealed herniation of the omentum into the vesico-vaginal space. The incarcerated hernia was repaired transvaginally, and the patient's symptoms improved.

Association of lymphadenectomy and survival in stage I ovarian cancer patients.

OBJECTIVE: To estimate the survival impact of lymphadenectomy in women diagnosed with clinical stage I ovarian cancer. METHODS: Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology and End Results Program between 1988 and 2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: A total of 6,686 women had clinical stage I ovarian cancer (median age 54 years, range 1-99). Of this total, 75.9% of patients were Caucasian, 8.3% were Hispanic, 5.8% were African American, and 7.3% were Asian. Epithelial tumors were present in 85.8% of the women, and 2,862 (42.8%) patients underwent lymphadenectomy. Patients aged 50 years or more were less likely to undergo lymphadenectomy compared with their younger cohorts (39.8% compared with 60.2%, P<.001). Only 32.7% of African-American women had lymphadenectomy compared with 42.7% of Caucasian women, 47.2% of Hispanics, and 48.8% of Asians (P<.001). Lymphadenectomy was associated with improved 5-year disease-specific survival of all patients from 87.0% to 92.6% (P<.001). More specifically, lymphadenectomy improved the survival in those with non-clear cell epithelial ovarian cancer (85.9% to 93.3%, P<.001) but not in those with clear cell carcinoma, germ cell tumors, sex cord stromal tumors, and sarcomas. Moreover, the extent of lymphadenectomy (0 nodes, less than 10 nodes, and 10 or more nodes) increased the survival rates from 87.0% to 91.9% to 93.8%, respectively (P<.001). On multivariable analysis, the extent of lymphadenectomy was a significant prognostic factor for improved survival, independently of other factors such as age, stage, histology, and grade of disease. CONCLUSION: Our data suggest that women with stage I non-clear cell ovarian cancers who underwent lymphadenectomy had a significant improvement in survival. LEVEL OF EVIDENCE: II.