Concurrent endometrial cancer in atypical endometrial hyperplasia and the role of sentinel lymph nodes: clinical insights from a multicenter experience.

OBJECTIVE: This study aimed to evaluate the prevalence of concurrent endometrial cancer in patients pre-operatively diagnosed with atypical endometrial hyperplasia undergoing hysterectomy. Additionally, we assessed the occurrence of high to intermediate-risk and high-risk tumors according to the ESGO-ESTRO-ESP classification. The study also compared surgical outcomes and complications between patients undergoing simple hysterectomy and those undergoing hysterectomy with sentinel lymph node biopsy. METHODS: In this multicenter retrospective study, patients with a pre-operative diagnosis of atypical endometrial hyperplasia were identified and divided into two groups: Group 1, which included patients treated with total hysterectomy with or without bilateral salpingo-oophorectomy, and Group 2, where sentinel lymph node biopsy was incorporated into the standard surgical treatment. RESULTS: Among 460 patients with atypical endometrial hyperplasia, 192 received standard surgical management (Group 1) and 268 underwent sentinel lymph node biopsy (Group 2). A total of 47.2% (95% CI 42.6% to 51.7%) of patients were upgraded to endometrial cancer on final histopathological examination. High to intermediate-risk and high-risk tumors constituted 12.3% and 9.2% in Group 2 and 7.4% and 3.7% in Group 1. Lymph node metastases were identified in 7.6% of patients with concurrent endometrial cancer who underwent nodal assessment with at least unilateral mapping. Of the 12 sentinel lymph node metastases, 75.0% were micrometastases, 16.7% macrometastases, and 8.3% isolated tumor cells. No significant differences were found in estimated blood loss, operative time, and intra-operative and post-operative complications between the two groups. The rate of patients undergoing sentinel lymph node biopsy doubled every 2 years (OR 2.010, p<0.001), reaching 79.1% in the last 2 years. CONCLUSION: This study found a prevalence of concurrent endometrial cancer of 47.2%, and sentinel lymph node biopsy provided prognostic and therapeutic information in 60.8% of cases. It also allowed for the adjustment of adjuvant therapy in 12.3% of high to intermediate-risk patients without increasing operative time or complication rates.

Effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer and atypical endometrial hyperplasia or endometrial intraepithelial neoplasia: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to evaluate the effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer (EC), atypical endometrial hyperplasia (AEH), or endometrial intraepithelial neoplasia (EIN). METHODS: Studies on hysteroscopic surgery combined with progesterone therapy for patients with early-stage EC, AEH, or EIN were searched from Embase, Web of Science, PubMed, and Cochrane Library databases. The included studies contained one or more of the following outcome variables: pregnancy rate, live birth rate, complete response (CR) rate, and recurrence rate after conservative treatment. The meta-analysis was performed using Stata. RESULTS: 13 pieces of literature containing 239 patients with EC and 199 patients with AEH/EIN were included. As per the results of meta-analysis, the pregnancy rates of EC patients and AEH/EIN patients were 49% (95% CI 33-65%) and 47% (95% CI 31-64%), respectively, and the live birth rates were 45% (95% CI 32-58%) and 44% (95% CI 34-54%), respectively. CR rates of EC patients and AEH/EIN patients were 90% (95% CI 85-94%) and 100% (95% CI 97-100%), respectively, and the disease recurrence rates were 17% (95% CI 8-28%) and 11% (95% CI 3-23%), respectively. CONCLUSION: Hysteroscopic surgery combined with progesterone was linked to an improved overall response rate, reduced disease recurrence rate, and increased pregnancy and live birth rates among patients with EC and AEH/EIN.

Increasing utilization of intrauterine device insertion at hysteroscopic endometrial evaluation for patients with endometrial hyperplasia.

PURPOSE: To examine the utilization and characteristics related to the use of hysteroscopy at the time of endometrial evaluation for endometrial hyperplasia in the outpatient surgery setting. METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample. The study population was 3218 patients with endometrial hyperplasia who underwent endometrial evaluation from January 2016 to December 2019. Performance and clinical characteristics of hysteroscopic endometrial evaluation were assessed with multivariable binary logistic regression models. RESULTS: A total of 2654 (82.5%) patients had hysteroscopic endometrial tissue evaluation. Patients with postmenopausal bleeding, heavy menstrual bleeding, and polycystic ovary syndrome were more likely to undergo hysteroscopic endometrial evaluation in multivariable analysis (all, adjusted-P < 0.001). Uterine injury occurred in 4.9 per 1000 hysteroscopic endometrial evaluations; none had uterine injury in the non-hysteroscopy cohort. Among the 2654 patients who had hysteroscopic endometrial evaluation, 106 (4.0%) patients had intrauterine device insertion at surgery, and the utilization increased from 2.9 to 5.8% during the study period (P-trend < 0.001). Younger age, more recent year surgery, and obesity were independently associated with increased utilization of intrauterine device insertion at hysteroscopic endometrial evaluation (all, adjusted-P < 0.05). Among 2023 reproductive-age patients with endometrial hyperplasia, 1666 (82.4%) patients underwent hysteroscopic endometrial evaluation. On multivariable analysis, patients with heavy menstrual bleeding were more likely to have hysteroscopic endometrial evaluation (adjusted-P < 0.05). Intrauterine device insertion increased from 3.7% in 2016 to 8.0% in 2019 (P-trend = 0.007). CONCLUSION: This nationwide analysis suggests that the insertion of intrauterine devices at the time of hysteroscopic endometrial tissue evaluation for endometrial hyperplasia is increasing among reproductive-age population.

Sentinel lymph node mapping in patients with endometrial hyperplasia: A practice to preserve or abandon?

OBJECTIVES: To compare outcomes of patients with premalignant endometrial pathology undergoing hysterectomy with or without sentinel lymph node (SLN) removal. Outcomes of interest included surgical adverse events (AEs), cancer status on final pathology, postoperative treatment, and The Cancer Genome Atlas (TCGA) molecular risk profiles. METHODS: We retrospectively identified patients with premalignant pathology on preoperative endometrial biopsy who underwent hysterectomy with or without SLN mapping/excision at our institution from 01/01/2017-12/31/2021. Clinical, pathologic, surgical, and TCGA profiling data were abstracted. Appropriate statistical tests were used. RESULTS: Of 221 patients identified, 161 (73%) underwent hysterectomy with SLN excision and 60 (27%) underwent hysterectomy without SLN excision. Median age and body mass index were similar between groups. Median operative time was 130 min for those who underwent SLN mapping/excision versus 136 min for those who did not (p = 0.6). Thirty-day postoperative AE rates were 9% (n = 15/161) and 13% (n = 8/60), respectively (p = 0.9). Ninety-eight (44%) of 221 patients had grade 1-2 endometrioid endometrial cancer on final pathology (4 [4%] were stage IB or higher). Ten (10%) of 98 patients, all within the SLN group, received adjuvant treatment. Among all patients, of 33 (15%) with TCGA molecular classification data, 27 (82%) had copy number-low, 3 (9%) microsatellite instability-high, 2 (6%) POLE-ultramutated, and 1 (3%) copy number-high disease. CONCLUSIONS: SLN assessment appears safe, detects a small number of occult nodal metastases for those upstaged, and provides additional staging information that can guide adjuvant treatment. SLN mapping should be discussed in preoperative counseling and offered using a shared decision-making approach.

Endometrial cancer patients understanding and interest in weight loss surgery.

OBJECTIVE: Obesity is a risk factor for endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and early type 1 endometrial cancer (EC) in 70%-90% of patients and is often a significant contributor to overall morbidity and mortality due to comorbidities. In 2011, bariatric surgery (BS) with lifestyle modification was identified as an intervention for reduction in overall mortality as well as risk for gynecologic cancers (Tsui et al., 2021). Our aim was to assess awareness of obesity as a risk factor and understanding of BS in an underinsured obese patient population with EC or EH. METHOD: This IRB-approved survey was distributed to patients with type I EC or EH within the past 5 years and a BMI >30. Questions addressed demographics, health habits, cancer and obesity awareness, as well as benefits and concerns about undergoing BS. Information was provided about dietary requirements after BS, and then interest in BS was surveyed. RESULTS: 61.2% of surveyed patients were interested in bariatric surgery for weight loss after receiving education about the procedure. Interest in bariatric surgery was correlated with higher BMI, higher ideal and comfortable weight loss in pounds and higher estimated weight loss that could be obtained with bariatric surgery. Additionally, patients who were interested in BS had better understanding of the risks of obesity with cancer overall. CONCLUSION: Obese patients with history of EC/EIN/EH are aware of hazards associated with excess weight and understand the relationship between EC/EIN/EH diagnosis and obesity, and overall are very interested in BS as a modality to improve their health.

Lymph node evaluation for endometrial hyperplasia: a nationwide analysis of minimally invasive hysterectomy in the ambulatory setting.

BACKGROUND: Given the possibility of occult endometrial cancer where nodal status confers important prognostic and therapeutic data, role of lymph node evaluation at hysterectomy for endometrial hyperplasia is currently under active investigation. The objective of the current study was to examine the characteristics related to lymph node evaluation at the time of minimally invasive hysterectomy when performed for endometrial hyperplasia in an ambulatory surgery setting. METHODS: The Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample was retrospectively queried to examine 49,698 patients with endometrial hyperplasia who underwent minimally invasive hysterectomy from 1/2016 to 12/2019. A multivariable binary logistic regression model was fitted to assess the characteristics related to lymph node evaluation at hysterectomy and a classification tree model with recursive partitioning analysis was constructed to examine the utilization pattern of lymph node evaluation. RESULTS: Lymph node evaluation was performed in 2847 (5.7%) patients. In a multivariable analysis, (i) patient factors with older age, obesity, high census-level household income, and large fringe metropolitan, (ii) surgical factors with total laparoscopic hysterectomy and recent year surgery, (iii) hospital parameters with large bed capacity, urban setting, and Western U.S. region, and (iv) histology factor with presence of atypia were independently associated with increased utilization of lymph node evaluation at hysterectomy (all, P < 0.05). Among those independent factors, presence of atypia exhibited the largest association for lymph node evaluation (adjusted odds ratio 3.75, 95% confidence interval 3.39-4.16). There were 20 unique patterns of lymph node evaluation based on histology, hysterectomy type, patient age, year of surgery, and hospital bed capacity, ranging from 0 to 20.3% (absolute rate difference, 20.3%). CONCLUSION: Lymph node evaluation at the time of minimally invasive hysterectomy for endometrial hyperplasia in the ambulatory surgery setting appears to be evolving with large variability based on histology type, hysterectomy modality, patient factors, and hospital parameters, warranting a consideration of developing clinical practice guidelines.

Efficacy and pregnancy outcomes of hysteroscopic surgery combined with progestin as fertility-sparing therapy in patients with early stage endometrial cancer and atypical hyperplasia.

PURPOSE: This study aims to evaluate the efficacy of hysteroscopic curettage combined with progestin therapy in young patients with early-stage endometrial cancer (EC) and endometrial atypical hyperplasia (EAH) who wished to preserve their fertility. METHODS: This prospective cohort study included 16 patients with early-stage EC and 25 patients with EAH in Dalian Maternal and Child Health Hospital from August 2014 to October 2018. All patients received fertility-sparing therapy with hysteroscopic evaluation every 3 months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed. RESULTS: There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91 months. BMI ≤ 30 kg/m2 was associated with shorter treatment duration to achieve CR (P = 0.003). Among the patients who attempted to conceive, 30.3% (10/33) had successful pregnancy, and 18.2% (6/33) delivered live births. The implementation of assisted reproductive technology (ART) is closely associated with pregnancy (P = 0.001). CONCLUSION: The fertility-sparing therapy, hysteroscopic curettage combined with progestin therapy, of early young EC and EAH patients is safe and effective. BMI is the main factor affecting the duration of CR. After achieving CR, ART can significantly improve the pregnancy rate of these patients.

The role of hysteroscopy in fertility preservation in endometrial cancer and atypical endometrial hyperplasia: a semi-systematic literature review.

PURPOSE: Endometrial premalignancies are among the common reasons for outpatient gynecology visits among women in reproductive ages. Due to the continued increase in global obesity incidence among them, endometrial malignancies are expected to become even further prevalent. Hence, fertility-sparing interventions are essential and needed. In this semi-systematic literature review, we aimed to investigate the role of hysteroscopy in fertility preservation in endometrial cancer and atypical endometrial hyperplasia. Our secondary goal is to analyze the pregnancy outcomes following fertility preservation. METHODS: We conducted a computed search in PubMed. We included original research articles including hysteroscopic interventions in pre-menopausal patients with endometrial malignancies and premalignancies who underwent fertility-preserving treatments. We collected data on medical treatment, response, pregnancy outcomes, and hysteroscopy. RESULTS: Of the query results (n = 364), our final analysis included 24 studies. Overall, 1186 patients with endometrial premalignancies and endometrial cancer (EC) were included. More than half of the studies were retrospective design. They included almost ten different forms of progestins. Of the reported pregnancies (n = 392), the overall pregnancy rate was 33.1%. The majority of the studies used operative hysteroscopy (87.5%). Only three (12.5%) reported their hysteroscopy technique in detail. Although more than half of the studies did not provide any information on adverse effects due to hysteroscopy, there were no serious adverse effects among the reported ones. CONCLUSION: Hysteroscopic resection may increase the success rate of fertility-preserving treatment of EC and atypical endometrial hyperplasia. The clinical significance of the theoretical concern of the dissemination of cancer is not known. Standardization of the use of hysteroscopy in fertility-preserving treatment is needed.

Hysteroscopic biopsy compared with endometrial curettage to assess the preoperative rate of atypical hyperplasia underestimating endometrial carcinoma.

PURPOSE: To evaluate the rate of atypical hyperplasia (AH) underestimating endometrial cancer (EC) comparing endometrial biopsy (EB) accomplished by hysteroscopic biopsy with dilatation and curettage (D&C). Second, to compare the two techniques to foresee EC grading. METHODS: This trial was based on the findings of two Gynecological Departments within the same Public Utility, sharing pathological service and database but routinely performing EB under hysteroscopic visualization (group A) or hysteroscopy followed by D&C (group B). We retrieved the clinical data of patients showing EC on hysterectomy throughout a 10-year period. The accuracy of hysteroscopic-view diagnosis and EB pathology were compared, having the pathologic findings of hysterectomy as reference. RESULTS: A total of 161 patients met the inclusion criteria. Among these, 109 and 52 were included in groups A and B, respectively. In group A, 32.1% of patients underwent EB in an out-patient setting. To foresee EC, hysteroscopic view showed a sensitivity of 82.5% and 70.2% in groups A and B, respectively (P = 0.019). An underestimation of EC diagnosed as AH on EB was found in 20 patients (12.4%). Among these, 18 (16.5%) and 2 (3.8%) were included in groups A and B, respectively (P = 0.022). In group A, a fault diagnosis of AH resulted higher when EB was performed as out-patient setting (P = 0.006). EB allowed the grading of EC in 73.3% and 90.3% of patients in groups A and B, respectively. The agreement was 73.7% and 85.1%, leading to moderate (κ = 0.56) and good (κ = 0.77) "κ" coefficient of concordance for groups A and B, respectively. CONCLUSIONS: EB performed by D&C lowers the rate of AH underestimating concurrent EC and improves the grading agreement when compared with hysteroscopic sampling.

Prognosis of patients with endometrial cancer or atypical endometrial hyperplasia after complete remission with fertility-sparing therapy.

PURPOSE: Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR. METHODS: We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy. RESULTS: The median follow-up duration was 34 months (range: 1-179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities. CONCLUSIONS: We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children.

[Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles].

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

Preliminary study of confocal laser endomicroscopy for in vitro specimens of the endometrium.

BACKGROUND: This study observed and described the morphological characteristics of the endometrium of the resected uterus using confocal laser endomicroscopy. This included benign endometrium, non-atypical endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma, thereby laying a foundation for finding the precise localization and resection of endometrial lesions, given the feasibility of confocal laser endomicroscopy-assisted hysteroscopy. METHODS: This prospective study included 32 patients who underwent hysterectomy. We used confocal laser endomicroscopy to observe the endometrium of resected uteruses and described the characteristics of endometrium in different states by comparing histopathological findings (primary objects). The secondary objects of observation were the myometrium, endocervical canal, and surface of the external os of the cervix. RESULTS: A total of 32 patients who underwent hysterectomy for different diseases were included: 9 with endometrial carcinoma (5 with endometrioid carcinoma, 1 with endometrial serous carcinoma, 2 with clear cell carcinoma, and 1 with carcinosarcoma), 2 with atypical endometrial hyperplasia, 9 with benign diseases, 7 with cervical cancer, and 5 with ovarian cancer and borderline tumor. The dynamic images of the endometrium were observed and recorded using probe-based confocal laser endomicroscopy (pCLE). Considering histopathology as the gold standard, the diagnostic concordance rate of pCLE was 96.9% in patients with endometrial carcinoma and precancerous lesions and 100% in patients with endometrial carcinoma. CONCLUSION: Confocal laser endomicroscopy provides real-time high-resolution images of the benign endometrium and endometrial lesions. Compared with histopathology, confocal laser endomicroscopy has high diagnostic accuracy and may become an auxiliary examination tool for hysteroscopy, as it is useful for early identification of endometrial lesions, real-time diagnosis of tumor, and detection of tumor boundaries for complete tumor resection. These findings can lay a foundation for the feasible use of fertility-sparing local excision of tumor lesions by hysteroscopy.

Substantial variability in ovarian conservation at hysterectomy for endometrial hyperplasia.

BACKGROUND: Although ovarian conservation at hysterectomy for benign gynecologic disease has demonstrated mortality benefit in young patients and this benefit may be sustained up to age 65 years, there is a scarcity of data regarding ovarian conservation in those with a diagnosis of endometrial hyperplasia, a premalignant uterine condition. OBJECTIVE: This study aimed to examine patient, hospital, treatment, and histology characteristics related to ovarian conservation at the time of inpatient hysterectomy for endometrial hyperplasia. STUDY DESIGN: The Healthcare Cost and Utilization Project's National Inpatient Sample was retrospectively queried to examine patients aged ≤65 years with endometrial hyperplasia who had inpatient hysterectomy from January 2016 to December 2019. The exclusion criteria included concurrent gynecologic malignancy, adnexal pathology, and lymphadenectomy. Cases were grouped by adnexal surgery status (ovarian conservation or oophorectomy). A multivariable binary logistic regression model was used to identify independent characteristics for ovarian conservation. A classification tree was constructed with recursive partitioning analysis to examine utilization patterns of ovarian conservation. RESULTS: Overall, 3105 patients (31.1%) underwent ovarian conservation at hysterectomy among 9975 patients. The utilization of ovarian conservation decreased gradually until age 45 years and then markedly decreased by age 52 years (63.3%-15.3%; P<.001). In a multivariable analysis, younger age, non-White, urban nonteaching centers, and vaginal hysterectomy were associated with increased utilization of ovarian conservation, whereas endometrial hyperplasia with atypia, obesity, comorbidity, large bed capacity centers, and Midwest and South regions were associated with decreased utilization of ovarian conservation (all, P<.05). A classification tree identified 17 utilization patterns for ovarian conservation, ranging from 7.8% to 100.0% (absolute rate difference, 92.2%). CONCLUSION: The utilization of ovarian conservation at the time of inpatient hysterectomy in patients undergoing surgical management for endometrial hyperplasia started decreasing in their mid-40s and seemed to occur earlier than in benign hysterectomy. There was substantial variability in ovarian conservation at the time of hysterectomy for endometrial hyperplasia based on patient, hospital, surgical, and histology factors, suggesting the possible benefit of clinical practice guidelines for ovarian conservation in this population.

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.

Navigating through perplex morphologic changes after exogenous hormone usage.

Clinical application of exogenous hormone as a method of contraception and/or treatment of various gynecologic disorders is exceedingly common. Unfortunately, the concurrent use of these agents also complicates the interpretation of pathology specimens. Various studies have shown that morphologic changes induced by hormonal therapies are present in both non-neoplastic and neoplastic tissues within the women's reproductive tract. It is important to understand the exogenous hormone induced morphologic changes, as it helps the pathologists make the accurate diagnosis, and in turn, guide clinicians to make optimal clinical decisions. In this review, we summarize the morphologic changes in both neoplastic and non-neoplastic endometrial, cervical, and myometrial surgical specimens after hormonal therapies, particularly after progestin treatment. In the endometrium, particularly in the scenario of progestin-treated atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN), there is notoriously poor interobserver agreement and difficulty in assessing for the residual disease. We summarize current literature and propose our recommended approach in assessing these challenging endometrial biopsies, including a diagnostic algorism, the use of PAX-2, PTEN, beta-catenin immunohistochemistry panel, as well as consistency in diagnostic wording of the report. In the cervix, progestin makes dysplastic lesions appear metaplastic, thus high-grade squamous dysplastic lesions may be easily missed. Within the myometrium, lesions such as adenomyosis may show various degree of decidualization, while smooth muscle neoplasms may show apoplectic changes, and stromal lesions including endometrial stromal sarcoma may show more eosinophilic cytoplasm. All such changes may pose more or less diagnostic challenges in our daily practice. However, most are readily recognizable when we understand particular hormone related scenarios.

Nodal Assessment in Endometrial Atypical Hyperplasia.

OBJECTIVE: Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25-50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging. METHODS: Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases. DESIGN: This was a retrospective study. RESULTS: Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (p = 0.01), hypertension (p < 0.01), and endometrial thickness ≥20 mm (p = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29-6.48) in AUB, 2.7 (95% CI: 1.06-6.92) in hypertension, and 3.1 (95% CI: 1.19-7.97) in endometrial thickness ≥20 mm cases. LIMITATIONS: The present study has limitations inherent in its retrospective nature. CONCLUSION: The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested.

Audit of waiting time-to-treatment of atypical endometrial hyperplasia.

BACKGROUND: Atypical endometrial hyperplasia (AEH) is the precursor lesion in endometrial carcinoma, the most common gynaecological malignancy in New Zealand, with inequities in disease burden and outcome for Maori and Pacific women. AIMS: In women diagnosed with AEH at two hospitals, to audit five standards of care for surgical management and time-to-treatment, and identify variation in care by ethnicity and other factors. MATERIALS AND METHODS: Demographic, referral, diagnostic and treatment characteristics were collected for women with a new AEH diagnosis between 1/1/2019 and 31/12/2020. Surgical management and time-to-treatment were audited against Royal College of Obstetricians and Gynaecologists and New Zealand Ministry of Health Faster Cancer Treatment recommendations. RESULTS: Of 124 participants, 60% were Pacific, 86% premenopausal, and 80% had obesity. For 55 women managed surgically, surgical standards of care were met. There were delays between referral, diagnosis and treatment - only 18% and 56% of women met the 62-day (referral to treatment) and 31-day (decision-to-treat to treatment) targets, respectively. Wait times were prolonged for women who had dilation and curettage (vs pipelle), magnetic resonance imaging (MRI) (vs no MRI), and surgery (vs medical management). Ethnic disparities were not identified for any standard. DISCUSSION: Delays to treatment were found throughout women's journeys. Hospital services can streamline their clinical pathways for women referred for abnormal uterine bleeding, flagging obesity as a high suspicion for cancer indicator, increasing access to endometrial sampling in primary care and establishing 'one-stop-shop' outpatient assessment with empiric initiation of intrauterine progestogen.

Uterine sparing management in patients with endometrial cancer: a narrative literature review.

Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in women who are younger than 40 years old. The survival rate in these cases is 99%; therefore, uterine-sparing management could be considered under strict criteria selection and the strong desire of the woman to preserve uterus and fertility. Diagnosis should be performed after a hysteroscopic biopsy instead of dilatation and curettage. The highest remission rate was achieved after combining a hysteroscopic resection with hormonal therapy compared to single hormonal treatment. The most common regiments are the following progestins: megestrol acetate (MA) and medroxyprogesterone acetate (MPA) taken orally with a daily dosage of 160 mg-320 mg for MA and 250 mg-600 mg for MP. Evaluations at three and six months could be performed by office endometrial biopsy and/or hysteroscopic directed biopsy especially in the presence of levonorgestrel intrauterine system, and in cases of remission, either a pregnancy attempt or maintenance therapy should be considered. After childbearing, hysterectomy with bilateral salpingo-oophorectomy is recommended, whereas ovarian preservation could be considered depending on the patient's age and whether they fulfil the strict criteria selection.

[Clinical outcomes analysis of fertility-preserving therapy for atypical endometrial hyperplasia and early endometrial carcinoma].

Objective: To analyze the clinical efficacy of fertility-preserving therapy in patients with atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC). Methods: The general condition, pathological type, treatment plan, tumor outcomes and pregnancy outcomes of 110 patients with AEH and EC treated with fertility-preserving therapy in Peking University People's Hospital from December 2005 to September 2019 were retrospectively analyzed. Kaplan-Meier and Log rank tests were used for survival analysis. Results: The response rate of 110 cases of AEH (62 cases) and EC (48 cases) was 94.5% (104/110) after fertility-preserving therapy. There were 93 cases (84.5%) achieved complete response and 11 cases (10.0%) achieved partial response, and the recurrence rate was 29.0% (27/93). The complete response rates of AEH and EC were 90.3% (56/62) and 77.1% (37/48), respectively, without significant difference (P=0.057). The recurrence rates of EC were significantly higher than that of AEH (40.5% vs 21.4%; P=0.022). Forty-one patients with complete response had pregnancy intention, the pregnancy rate was 70.7% (29/41), and the live birth rate was 56.1% (23/41). The live birth rate of AEH was 68.2% (15/22) and that of EC was 42.1% (8/19), the difference was statistically significant (P=0.032). The pathological type was related with the recurrence (P=0.044). Conclusions: Patients with AEH and EC can obtain high complete response rate and pregnancy rate after fertility-preserving therapy. The recurrence rate of EC is higher than that of AEH, while the live birth rate of AEH is higher than that of EC.

Lymph node assessment at the time of hysterectomy has limited clinical utility for patients with pre-cancerous endometrial lesions.

OBJECTIVE: The objective of this study was to determine the proportion of patients with a pre-invasive endometrial lesion who meet Mayo criteria for lymph node dissection on final pathology to determine if the use of sentinel lymph node biopsy in patients with pre-invasive lesions would be warranted. METHODS: All women who underwent hysterectomy for a pre-invasive endometrial lesion (atypical hyperplasia or endometrial intra-epithelial neoplasia) between 2009 and 2019 were included for analysis. Relevant statistical tests were utilized to test the associations between patient, operative, and pathologic characteristics. RESULTS: 141 patients met inclusion criteria. 51 patients (36%) had a final diagnosis of cancer, the majority (96%) of which were Stage IA grade 1 endometrioid carcinomas. Seven patients (5%) met Mayo criteria on final pathology (one grade 3, seven size >2 cm, one >50% myoinvasive). Three of these seven patients had lymph nodes assessed of which 0% had metastases. Six of these patients had frozen section performed, and 2 met (33%) Mayo criteria intraoperatively. Of the seven patients in the overall cohort that had lymph node sampling, six had a final diagnosis of cancer and none had positive lymph nodes. Of the 51 patients with cancer, only 10 had cancer diagnosed using frozen section, and only two met intra-operative Mayo criteria. Age > 55 was predictive of meeting Mayo criteria on final pathology (p = 0.007). No patients experienced a cancer recurrence across a median follow up of 24.3 months. CONCLUSIONS: Atypical hyperplasia and endometrial intra-epithelial neoplasia portend low risk disease and universal nodal assessment is of limited value.