Extrauterine Spread Research Articles

Abstract 7061: Targeting metabolic vulnerabilities in ARID1A/B dual-deficient dedifferentiated endometrial carcinoma

Abstract Background: Dedifferentiated endometrial carcinoma (DDEC) is an aggressive endometrial carcinoma defined histologically by undifferentiated carcinoma juxtaposed against stage 1 or 2 endometrial adenocarcinoma. DDEC responds poorly to conventional platinum/taxane-based chemotherapy, particularly in the case of extrauterine spread. This highlights a need to develop novel therapies for individuals with DDEC. Genetically, a third of DDEC cases have co-inactivating mutations of ARID1A and ARID1B. These genes encode core subunits of the sucrose/switch non-fermentable (SWI/SNF) complex that regulate transcription. Furthermore, dual loss of ARID1A/B is believed to play a role in driving DDEC tumor development. We hypothesize that ARID1A/B dual-deficiency in DDEC generates unique genetic deficiencies that allow for the development of novel therapies for this cancer. We approached this hypothesis by first conducting a preliminary analysis of the Cancer Dependency Map (DepMap), which has identified vulnerabilities in mitochondrial functioning in ARID1A/B dual-deficient DDECs. As such, we aimed to understand the role of mitochondrial oxidative phosphorylation (OXPHOS) and redox homeostasis in ARID1A/B dual-deficient DDEC to create new treatment options. Methods: A panel of ARID1A/B dual-deficient and proficient endometrial cancer cell lines were treated with OXPHOS inhibitor IACS-010759 and reactive oxidative species (ROS)-inducing agent elesclomol to identify shifts in drug response between the two groups. To account for genomic differences between the cell lines, we also treated an ARID1B knock-out isogeneic cell line with the drugs. Additionally, changes in metabolism in the endometrial cancer cell lines were measured using Seahorse metabolic flux assays to determine if ARID1A/B dual-deficient cell lines have an increased dependency on OXPHOS for cell growth. Results: While the Seahorse assays revealed no significant difference in OXPHOS and glycolysis activities between the two groups, drug sensitivity assays demonstrated that ARID1A/B dual-deficient cancers are more sensitive to OXPHOS inhibition and increased ROS production than the proficient cell lines. Depletion of ARID1B in an ARID1A deficient cell line sensitizes the cells to both drugs. Furthermore, IACS-010759 significantly suppressed the growth of ARID1A/B-deficient DDEC xenograft tumor growth. Conclusion: ARID1A/B-dual deficient cancer cells rely on mitochondria function for survival. The underlying mechanisms are currently under investigation. Citation Format: Rebecca Ho, Eunice Li, Chae Young Shin, Shary Chen, David Huntsman, Yemin Wang. Targeting metabolic vulnerabilities in ARID1A/B dual-deficient dedifferentiated endometrial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7061.

Abstract IA012: The role of the serine/threonine phosphatase PP2A in endometrial cancer development and progression: lessons learned from mutations and small molecules

Abstract Uterine cancer is the most common gynecologic malignancy in the United States with approximately 60,000 new diagnoses each year. While many cases of uterine endometrial carcinoma (EMCA) have favorable outcomes with recurrence-free long-term survival, outcomes for the high-grade, treatment-refractory histological subtypes, including uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS), remain an important clinical problem. Uterine serous carcinomas and uterine carcinosarcomas tumors are the most aggressive subtypes of uterine cancer, displaying a high propensity to invade the peritoneal cavity and to metastasize to distant sites. Accordingly, 50-70% of high-grade tumors exhibit extrauterine spread at time of initial surgery and have limited treatment options. The inherent aggressiveness of these tumors suggests that they are intrinsically equipped to disseminate and propagate tumors at secondary sites. The molecular drivers of this phenotype, however, have yet to be completely characterized. A lack of established and validated molecular drivers of the high-grade subtypes, especially those that are responsible for the high rate of metastasis, has limited the use of targeted treatment strategies. However, we and other groups have shown that PPP2R1A, the scaffolding subunit of the tumor suppressor protein phosphatase 2A, is mutated in up to 40% of USC patients, and these recurrent mutations are found at both the primary and metastatic sites. These mutations are heterozygous, and two specific mutations: P179R and S256F, occur exclusively within these high-grade subtypes of uterine cancer (i.e., are not found in any other cancer type). PP2A, is a family of serine/threonine phosphatases, where the active heterotrimeric form of the enzyme is comprised of a catalytic (C) subunit, a scaffolding (A) subunit, and a substrate directing regulatory (B) subunit. In aggregate, PP2A is considered a tumor suppressor protein, but certain heterotrimers have tumor promoting roles. Here we present data related to the molecular and biological basis through which these recurrent pathogenic mutations drive endometrial cancer development and progression using disease relevant cellular and in vivo model systems. Additionally, building from previously published work from our group, we have developed a novel series of small molecule molecular glues (PMGs) that specifically correct the mutant heterotrimer driving tumor regressions in both cellular and patient derived xenograft models of high-grade endometrial cancer. Collectively, this data suggests that recurrent pathogenic mutations in the PPP2R1A gene drive endometrial cancer pathogenesis and these mutations can be therapeutically targeted using a series of pharmaceutically tractable small molecules. Citation Format: Goutham Narla. The role of the serine/threonine phosphatase PP2A in endometrial cancer development and progression: lessons learned from mutations and small molecules [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA012.

A phase II trial evaluating the efficacy and safety of repeated high dose medroxyprogesterone acetate (MPA) therapy for patients with recurrent early-stage endometrial cancer or atypical endometrial hyperplasia: Japanese Gynecologic Oncology Group study (JGOG2051/KGOG2031, REMPA trial).

Fertility preserving therapy using medroxyprogesterone acetate (MPA) is an important option for young patients with endometrial cancer or atypical endometrial hyperplasia (AEH). However, the effectiveness and feasibility of repeated MPA therapy for patients with intrauterine recurrence following initial MPA therapy is controversial. Only a few single-institution retrospective studies have been conducted on repeated MPA therapy, therefore, multicenter prospective studies for repeated MPA therapy are highly needed. The aim of this study is to assess whether repeated MPA therapy is effective and feasible for patients with intrauterine recurrence following initial MPA therapy. This is a prospective, single-arm, a multicenter phase II trial on repeated MPA therapy for intrauterine recurrence following fertility-preserving therapy for AEH or stage IA (the International Federation of Gynecology and Obstetrics [FIGO] 2008) non-myoinvasive endometrioid carcinoma grade 1. Patients are treated with oral MPA (500-600 mg/day). Pathologically assessment via dilation and curettage will be performed every 2 months until complete response. The major inclusion criteria are 1) intrauterine recurrence of AEH or stage IA (FIGO 2008) endometrioid carcinoma grade 1 without myometrial invasion or extrauterine spread confirmed by imaging tests after complete remission with the previous MPA therapy. 2) The number of recurrences should be up to twice. 3) histologically diagnosed as AEH or endometrioid carcinoma grade 1, 4) 20-42 years of age, and 5) strong desire and consent for fertility-sparing treatment. The primary endpoint is 2-year recurrence-free survival rate. A total of 115 patients will be enrolled from multiple institutions in Japan and Korea within 4 years and followed up for 2 years. Japan Registry of Clinical Trials Identifier: jRCTs031200256.

A model for predicting extrauterine tumor spread in patients with endometrial cancer

A model for predicting extrauterine tumor spread in patients with endometrial cancer
 
 Abstract
 Background: The factors predicting extrauterine spread in patients undergoing staging surgery with the diagnosis of endometrial cancer were investigated. 
 Aims: The study aimed to create a model using demographic, surgical, and pathological factors to predict extrauterine spread.
 Methods: Included in the study were 355 patients with a final diagnosis of endometrial cancer who underwent surgery for staging purposes. The effect of surgical-prognostic factors on extrauterine spread was analyzed using univariate analysis and multivariate logistic regression analysis.
 Results: Extrauterine spread was detected in 97 patients. A multivariate logistic regression model that was created to determine the factors affecting extrauterine spread identified the presence of lymphovascular invasion, cervical invasion, peritoneal cytology positivity and tumor type as independent factors. A model was created using these four independent risk factors. According to this model, the rate of extrauterine spread was 6.4% in patients who did not have the risk factors and 100% in patients who had all the risk factors (p

Pulmonary benign metastasizing leiomyoma in patients aged 45 years and younger: clinical features and novelty in treatment

BackgroundPulmonary benign metastasizing leiomyoma (PBML) is the most common extrauterine spread of uterine leiomyoma, and its biological behavior is traditionally thought to be hormone dependent. Studies on older PBML patients have been previously reported, but limited literature has been published regarding the clinical features and treatment of PBML in young women.MethodsA total of 65 cases of PBML in women aged 45 years and younger were reviewed, including 56 cases selected from PubMed and 9 cases from our hospital. The clinical characteristics and management of these patients were analyzed.ResultsThe median age of all the patients at diagnosis was 39.0 years. PBML most commonly presented as bilateral solid lesions (60.9%), with other rare imaging manifestations. The median interval time from a pertinent gynecologic procedure to diagnosis was 6.0 years. A total of 16.7% of patients received careful observation, and all achieved stable status in a median follow-up time of 18.0 months. A total of 71.4% of patients were administered anti-estrogen therapies, including surgical castration (33.3%), gonadotropin-releasing hormone analog (23.8%) and anti-estrogen drugs (14.3%). Eight of 42 patients underwent surgical resection of metastatic lesions. Patients who underwent curative surgery for the removal of pulmonary lesions combined with adjuvant anti-estrogen therapies had favorable outcomes compared with those who only underwent surgical resection. The disease control rates of surgical castration, gonadotropin-releasing hormone analog, and anti-estrogen drugs were 85.7%, 90.0%, and 50.0%, respectively. For two patients, sirolimus (rapamycin) achieved successful relief of symptoms and control of pulmonary lesions without lowering hormone levels and causing estrogen deficiency symptoms.ConclusionsIn the absence of standard treatment guidelines for PBML, maintaining a low-estrogen environment using different kinds of antiestrogen therapies has been the mainstream strategy and has satisfying curative effects. A wait-and-see strategy might be an option, but therapeutic approaches must be contemplated when complications or symptoms progress. For PBML in young women, the negative effect on ovarian function of anti-estrogen treatment, especially surgical castration, should be considered. Sirolimus might be a new treatment option for young PBML patients, especially for those who want to preserve ovarian function.

Serous endometrial intra-epithelial carcinoma: an observational study

BackgroundSerous endometrial intra-epithelial carcinoma is described as a malignant, superficial spreading lesion with risk of extra-uterine spread at time of diagnosis, and poor outcome.ObjectiveTo evaluate the surgical management of patients...

The association of polypoid growth pattern with lymph node involvement in endometrioid type endometrial adenocarcinoma.

Tumor size is an independent predictor of lymph node metastasis and survival in the endometrioid type endometrial adenocarcinoma (EC). However, some of the ECs tend to grow towards the cavity in the polypoid pattern, which can reach very large sizes. In this study, we aimed to analyze the association of growing in the polypoid pattern of the tumor with the proportion of lymph node metastasis and extrauterine tumor spread. Four hundred seven patients were analyzed retrospectively. The effect of tumor size, tumor growing pattern, myometrial invasion, grade, and lymphovascular space invasion on the lymph node metastasis and extrauterine tumor spread were investigated. Statistical analysis consisted of unpaired t-tests for parametric data and Mann Whitney-U test for non-parametric data, whereas the Chi-square test for categorical variables. Logistic Regression, Cox Regression and multivariate analysis were used to estimate the risk predictors. No association was found between the growing in polypoid pattern and lymph node metastasis (P > 0.05). In the analysis of endometrioid type EC patients who had myometrial invasion less than ½ as a subgroup, no association was found between the growing pattern and lymph node metastasis and extrauterine disease. Tumor size was found to be a statistically significant predictor of lymph node metastasis and extrauterine disease (P < 0.05). Lymphovascular space invasion, grade, and myometrial invasion are associated with a higher proportion of lymph node metastasis. The polypoid growth pattern of the tumor does not correlate with any histopathological parameters.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

ObjectiveTo determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. MethodsRetrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. ResultsOne hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2–3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. ConclusionsInformation from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Minimally Invasive Technique Not Associated with Worse Prognosis in Patients with Stage I Uterine Papillary Serous Carcinoma (UPSC)

Study Objective To determine the role of surgical technique in increasing risk of recurrence in patients with stage I UPSC. Design Using a prospective database and billing records, all cases of UPSC were identified from 2006 through 2021. Standard statistical analysis related the impact of surgical technique and BTL on recurrence risk and progression free survival (PFS) in patients with stage I UPSC. Setting N/A. Patients or Participants All patients with UPSC diagnosed at our center 2006-2021. Interventions N/A. Measurements and Main Results A total of 225 total cases of UPSC were identified, including 118 pts with stage I disease. Six patients (5%) had endometrial intraepithelial carcinoma (EIC), 98 (83%) were stage IA, and 14 (12%) were stage IB. A history of BTL was obtained in 25 pts (21%). Minimally invasive hysterectomy was performed in 99 (84%; 31% robot, 53% laparoscopy). Adjuvant chemotherapy was given to 83 patients (72%) with 31 (256%) receiving 3 cycles or less and 54 (46%) receiving 4-7 cycles. Additionally, 22 (19%) received vaginal brachytherapy and 9 (8%) received whole pelvic radiation. Seventeen patients (14%) experienced recurrence after treatment and 8 (7%) died of disease. No differences in PFS or outcomes were noted between open and minimally invasive methods (P=0.76). Patients who underwent BTL prior to diagnosis were found to have a recurrence rate of 28% vs. 11% in patients without history of BTL (P = 0.03). A multivariate model incorporating known risk factors for recurrence, including use of radiation, chemotherapy, depth of invasion, and LVSI, confirmed that BTL remained a significant predictor of recurrence (OR 3.18; 95% CI 1.02-9.96, P = 0.046). Conclusion No differences in progression free survival were noted between patients who underwent minimally invasive vs. open surgeries in patients with stage I UPSC. However, BTL does not appear to be protective against extra-uterine spread and may change the presenting stage of biologically more aggressive tumors. To determine the role of surgical technique in increasing risk of recurrence in patients with stage I UPSC. Using a prospective database and billing records, all cases of UPSC were identified from 2006 through 2021. Standard statistical analysis related the impact of surgical technique and BTL on recurrence risk and progression free survival (PFS) in patients with stage I UPSC. N/A. All patients with UPSC diagnosed at our center 2006-2021. N/A. A total of 225 total cases of UPSC were identified, including 118 pts with stage I disease. Six patients (5%) had endometrial intraepithelial carcinoma (EIC), 98 (83%) were stage IA, and 14 (12%) were stage IB. A history of BTL was obtained in 25 pts (21%). Minimally invasive hysterectomy was performed in 99 (84%; 31% robot, 53% laparoscopy). Adjuvant chemotherapy was given to 83 patients (72%) with 31 (256%) receiving 3 cycles or less and 54 (46%) receiving 4-7 cycles. Additionally, 22 (19%) received vaginal brachytherapy and 9 (8%) received whole pelvic radiation. Seventeen patients (14%) experienced recurrence after treatment and 8 (7%) died of disease. No differences in PFS or outcomes were noted between open and minimally invasive methods (P=0.76). Patients who underwent BTL prior to diagnosis were found to have a recurrence rate of 28% vs. 11% in patients without history of BTL (P = 0.03). A multivariate model incorporating known risk factors for recurrence, including use of radiation, chemotherapy, depth of invasion, and LVSI, confirmed that BTL remained a significant predictor of recurrence (OR 3.18; 95% CI 1.02-9.96, P = 0.046). No differences in progression free survival were noted between patients who underwent minimally invasive vs. open surgeries in patients with stage I UPSC. However, BTL does not appear to be protective against extra-uterine spread and may change the presenting stage of biologically more aggressive tumors.

Outcomes and Patterns of Failure in Early-Stage, High-Risk Histology Endometrial Cancer Treated with Vaginal Cuff Brachytherapy

<h3>Purpose/Objective(s)</h3> The majority of patient diagnosed with endometrial cancer have low-risk endometrioid histology with an excellent prognosis. There is a small subset of patients however, who are diagnosed with a histology for which the outcomes are not as good. Serous, clear cell, carcinosarcoma and neuroendocrine carcinomas are more aggressive histological variants with a propensity for early extrauterine spread resulting in higher rates of death. They typically receive upfront chemotherapy but questions remain as to whether the increased risk of spread warrants adjuvant pelvic radiation or whether the risk can be mitigated with vaginal cuff brachytherapy (VCB). We aim to describe the outcomes and patterns of failure in early-stage, high-risk histology patients in which pelvic radiation was omitted, in order to shed light on the risk of pelvic failure. <h3>Materials/Methods</h3> A retrospective chart review was performed on patients treated for high-risk histology, early-stage uterine cancer at our institution. Patients receiving adjuvant VCB +/- chemotherapy were included. Demographic and clinical data was collected. Descriptive statistics were used to summarize variables. Kaplan-Meier analysis was used to estimate the survival probabilities. For all time to event outcomes, univariate cox proportional hazard regression models were built for clinically correlated variables. A two-tailed p<0.05 was considered statistically significant. <h3>Results</h3> 77 patients with early-stage carcinosarcoma (23.4%), clear cell (35.1%), serous (40.3%) and neuroendocrine carcinoma (1.3%) of the uterus were reviewed. Median follow up was 43 months (range 7-117 months). 2yr and 5yr overall survival (OS), metastasis free survival (MFS) and progression free survival (PFS) were 95% and 92%, 95% and 90% and 91% and 82% respectively. Of the 9 patients (11.7%) that recurred, 2 patients (2.6%) had isolated vaginal cuff recurrences, 4 patients (5.2%) had isolated pelvic recurrences and 3 patients (3.9%) had both a local and distant failure. Of the 27 individual sites of recurrence, 21 (77.8%) were below the level of L4. <h3>Conclusion</h3> In patients with early stage, high risk histology endometrial cancer treated with adjuvant VCB +/- chemotherapy, the 2yr and 5yr PFS was 91% and 82% respectively. All patients that recurred had some component of pelvic failure.

Role of MRI in pre-operative staging of endometrial cancer: A diagnostic accuracy study

Endometrial cancer (EC) is a commonly occurring cancer among post-menopausal women. Pre-treatment imaging of the extent of disease can influence the decisions in the management of EC. MRI with its diffusion weighted (DW) images can help in better depiction of the primary tumour, its local extension and extrauterine spread to the peritoneum and lymph nodes. This study was conducted to know the role of MRI for pre-operative staging of endometrial cancer and as a guide for pelvic lymph nodal dissection.It was a descriptive cross-sectional study conducted at a tertiary care hospital patients diagnosed with primary endometrial adenocarcinoma on biopsy. Patients with advanced disease requiring chemotherapy prior to surgery were excluded. Fifty consecutive patients were subjected to MRI Pelvis with abdominal screening in the week preceding definitive surgery, Findings from imaging were compared with final histopathology for concurrence on tumour size, depth of myometrial invasion, presence of adnexal, nodal and cervical stromal involvement.Majority of the patients in this study were post-menopausal women. Sensitivity of MRI for staging of Endometrial Carcinoma in this study was 91.84% and Accuracy was 90%. When compared to HPE for lymph node positivity, MRI had sensitivity of 100%, specificity of 97.87%, PPV of 75%, NPV of 100% and accuracy of 98%.Pre-operative MRI in the week prior to the planned surgery can help in accurately staging the endometrial carcinoma in terms of myometrial infiltration, cervical stromal infiltration as well as pelvic lymph nodal involvement.

Retreatment with progestin for recurrence after achieving complete response with fertility sparing hormonal treatment in patients with early endometrial cancer (095)

<b>Objectives:</b> To assess the outcomes of retreatment using progestin in patients with recurrent endometrial cancer (EC) after achieving complete response (CR) with fertility-sparing hormonal treatment. <b>Methods:</b> We retrospectively reviewed patients who had recurrence after achieving CR by fertility-sparing treatment using progestin with presumed stage IA, grade 1, endometrioid EC from 2005 to 2020. All recurrent patients were given medroxyprogesterone acetate or megestrol acetate with concurrent LNG-IUD. The primary endpoint was a response rate. The secondary endpoints were pregnancy outcome, pathologic disease progression, and 2^nd recurrence rate. <b>Results:</b> Of 55 recurrent patients, 50 received progestin retreatment. With a median retreatment duration of eight (3-56) months, the CR rate of the retreatment group was 78% (39/50); 76.2% in the EC group, and 87.5% in the endometrial intraepithelial neoplasia group. Of 11 patients not achieving CR to progestin retreatment, three underwent surgical treatment, and none had extrauterine spread of disease. Of twenty patients who attempted to conceive after achieving CR, ten became pregnant. These pregnancies resulted in three (30%) abortions, one (10.0%) preterm (12.5%), and six (60%) full-term births. Of the 39 patients achieving CR after 1^st recurrence, 18 (46.1%) patients had 2^nd recurrence with a median follow-up duration of 14 (3-36) months. Of those, 15 patients received second-line progestin retreatment, and nine (60%) of these patients achieved CR. All patients who underwent retreatment are alive without evidence of disease. <b>Conclusions:</b> First-line and second-line progestin retreatment in patients with recurrent endometrial cancer are as effective and safe as initial fertility-sparing treatment. Therefore, it may provide an opportunity to young patients who still want to preserve fertility after recurrence.

CA-125 seviyeleri, Endometrial seröz karsinomun uterus dışı yayılımının dışlanmasında ne kadar spesifiktir?

Abstract&#x0D; Aim: To investigate the CA-125 levels in uterine serous carcinoma (UPSC) patients to predict the extent of disease.&#x0D; Materials and Method: Medical records of patients operated for UPSC/mix serous carcinoma, endometrioid carcinoma; their preoperative CA-125 levels, as well as parameters including age, tumor size, lymph node involvement, lymphovascular space invasion (LVSI), depth of myometrial invasion (MI) and stage were documented.&#x0D; Results: Twenty-six UPSC/mix serous carcinoma cases and forty-five endometrioid carcinoma cases were included. When we analyzed the serous cancer group in terms of CA-125; there was no association between CA-125 and age (≤60 vs &gt;60), tumor size (≤40 vs &gt;40mm), MI, lymph node metastasis or LVSI. The mean CA-125 levels were significantly higher among patients with stage III/IV (median=54 U/ml), compared to stage I/II (median=11 U/mL). The mean CA-125 value for tumors spread beyond the uterus were 281.2 U/ml, and 14.3 U/ml for the tumors confined within the uterus (p=0.002). The optimum threshold value to predict extrauterine spread was 28.5 U/mL. CA-125 level was related to extrauterine involvement and advanced stage.&#x0D; Conclusion: CA-125 level is a useful test for extrauterine involvement and advanced stage. We suggest a less aggressive treatment modality with CA-125

Retreatment with progestin for recurrence after complete response with fertility-sparing treatment in patients with endometrial cancer

ObjectiveTo assess the outcomes of retreatment using progestin for recurrence after a complete response with fertility-sparing treatment in patients with early endometrial cancer.MethodsWe retrospectively reviewed the data of patients with...

Comparison between 1.5-T and 3.0-T MRI for the diagnosis of placenta accreta spectrum disorders

PurposeAccurate antenatal diagnosis of placenta accreta spectrum (PAS) is important for optimal management. The purpose of this study was to compare the respective capabilities of 1.5-T and 3.0-T MRI in the diagnosis of PAS. Materials and methodsBetween March 2016-March 2021, 190 pregnant women at high risk for PAS underwent dedicated prenatal MRI with either 1.5-T or 3.0-T units at a tertiary imaging center. Cesarian section and MRI were performed less than 6 weeks from each other. Prospectively collected data were evaluated by two experienced genitourinary radiologists for presence and extent of PAS. A comparative study was designed to investigate differences in predictive ability between 1.5-T and 3.0-T MRI groups. Sensitivity, specificity, accuracy, negative and positive prognostic values relative to intraoperative/histological findings, were computed for both groups and were compared with chi-square (χ 2) test. Interobserver agreement was estimated using Kappa test. ResultsOne hundred-eighty-two gravid women were included in the study; of these, 91/182 (50%) women were evaluated with 1.5-T (mean age, 35 ± 5.1 [SD] years; mean gestational age: 32.5 weeks) and 91/182 (50%) with 3.0-T MRI (mean age, 34.9 ± 4.9 [SD] years; mean gestational age, 32.1 weeks). 1.5-T MRI yielded 95.7% sensitivity (95% CI: 87.8–99.1) and 81.8% specificity (95% CI: 59.8) and 3.0-T MRI 93.8% sensitivity (95% CI: 86.0–97.9) and 83.3% specificity (95% CI: 48.2–97.7) for PAS identification, with no differences between the two groups (P = 0.725 and P >0.999, respectively). MRI showed excellent predictive ability for detecting extrauterine placental spread with 100% sensitivity (95% CI: 89.4–100.0), 96.7% specificity (95% CI: 88.1–99.6) for 1.5-T and 97% sensitivity (95% CI: 84.2–99.9), 96.7% specificity (95% CI: 88.1–99.6) for 3.0-T without differences between the two groups (P > 0.999). Interobserver agreement was excellent for both groups. The most frequently detected MRI signs of PAS for both 1.5-T and 3.0-T groups were placental heterogeneity (n = 85, 93.5% vs. n = 90, 98.9%; P = 0.413), and intraplacental fetal vessels (n = 64, 70.3% vs. n = 65, 71.4%; P = 0.870). ConclusionThis study suggests that 3.0-T MRI and 1.5-T MRI are equivalent for the diagnosis of PAS.

Endometrial Stromal Sarcomas With BCOR Internal Tandem Duplication and Variant BCOR/BCORL1 Rearrangements Resemble High-grade Endometrial Stromal Sarcomas With Recurrent CDK4 Pathway Alterations and MDM2 Amplifications.

The distinction between low-grade and high-grade endometrial stromal sarcomas (LGESS, HGESS) is increasingly defined by genetics. Recently, variant genomic alterations involving BCOR or BCORL1 have been reported in endometrial stromal sarcoma (ESS), although it remains unclear whether these justify a diagnosis of LGESS or HGESS. In this study, we describe clinicopathologic and molecular features of ESS with such alterations to help clarify their classification in the spectrum of ESS. We collected a cohort of 13 ESS harboring variant alteration involving BCOR (6 with internal tandem duplication, 1 with EP300::BCOR fusion, 1 with BCOR::LPP fusion) and BCORL1 ( 4 with JAZF1::BCORL1 fusion, 1 with EPC1::BCORL1 fusion). The median patient age at primary diagnosis was 51 years (range: 18 to 70 y). Median tumor size at primary diagnosis was 9.3 cm (range: 4.5 to 21 cm), and extrauterine disease spread (stage IIIB-C) was present in 27%. The tumors were composed of round to spindled cells with cellularity and cytologic atypia ranging from mild to marked and a median mitotic count of 18/10 HPFs (range: 2 to 85/10 HPFs). At least focally myopermeative growth was noted in 8/8 assessable cases. Of 12 patients with follow-up data (median: 25 mo), 4 patients died of disease and 3 were alive with recurrent disease. Unsupervised hierarchical clustering of DNA methylation data together with a large cohort of uterine mesenchymal tumors that included YWHAE::NUTM2 and Z C3H7B::BCOR HGESS and molecularly confirmed LGESS revealed a common methylation signature for all ESS with variant BCOR and BCORL1 alterations and HGESS with YWHAE::NUTM2 and ZC3H7B::BCOR gene fusion. Copy number analysis revealed amplifications of CDK4 and MDM2 , as well as homozygous deletions of CDKN2A/B and NF1 in a subset of tumors. Our results indicate that ESS with BCOR internal tandem duplication and variant BCOR and BCORL1 rearrangements clinically and molecularly resemble conventional HGESS.

Does Gas Insufflation during Gynecologic or Urologic Oncologic Laparoscopy Cause Dissemination of Malignant Cells

<h3>Study Objective</h3> To investigate whether benign or malignant cells are found in evacuated gas during laparoscopy for gynecological or urological malignancies. <h3>Design</h3> Observational prospective study. <h3>Setting</h3> Academic, tertiary medical center. <h3>Patients or Participants</h3> A total of 30 patients were included; 15 underwent laparoscopic staging due to uterine adenocarcinoma and 15 had laparoscopic nephrectomy due to suspected renal cell carcinoma. <h3>Interventions</h3> All gas evacuated during laparoscopy was passed through a filter in order to capture any aerosolized cells formed during surgery. After surgery, the filter was rinsed backwards with 50 CC of normal saline. The fluid was collected, centrifuged and sent for cytological evaluation. Filter ability to capture malignant cells was proved by filtering ascites fluid of an ovarian cancer patient through the filter. The primary outcome was the rate laparoscopic surgeries in which the filtered sample was positive for malignant or benign cells. <h3>Measurements and Main Results</h3> No benign or malignant cells were identified in evacuated gas during laparoscopic surgeries in all but one case. This case of malignant adenocarcinoma had a clear, macroscopic extra-uterine pelvic spread and malignant adenocarcinoma cells were identified in the cytology examination of the fluid collected. <h3>Conclusion</h3> In contrast to previous concerns, in all cases where the tumor was confined to its' organ, we found no evidence of benign or malignant cell spread in the gas evacuated from the abdominal or retroperitoneal cavity during laparoscopy. The single event of malignant cells from aerosolized gas was in a case with a macroscopic, extra-organ involvement. Our study confirms the safety of performing laparoscopic surgery for gynecologic and urologic malignancies with regard to aerosolized gas. The explanation for malignant cells found in evacuated gas could be both aerosolization of cells or cells that adhered to surgical instruments. The clinical significance of this finding in the setting of macroscopic, extra-organ tumor spread is unclear.

Clinical and molecular pathological features of uterine inflammatory myofibroblastic tumor

Objective: To evaluate the clinical and molecular pathologic features of uterine inflammatory myofibroblastic tumor (UIMT). Methods: Six UIMT cases collected at Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University from 2019 to 2020. They were analyzed for their general characteristics and clinicopathologic features. ALK rearrangements were detected by fluorescence in situ hybridization. Results: The age of the six patients ranged from 14 to 65 years, the tumors ranged in size from 2.5 to 6.0 cm. The masses were intramural or submucosal in location. Most of them (4/6) were white with yellow foci, and two (2/6) were white with tan foci. Other features noted included a soft or firm appearance. The fasciitis-like pattern of UIMT had myxoid stroma around the spindle cells and inflammatory cells. The ganglion-like pattern showed either fascicular or storiform architecture with diffuse growth. Nuclear atypia was mild or moderate. Mitoses ranged from 2 to 4 per 10 high-power fields. Five tumors were ALK-positive with granular cytoplasmic staining by immunohistochemistry. ALK rearrangements were detected in five cases but was absent in one case. Conclusions: UIMT is an intermediate grade soft tissue tumor, a minority may present with extrauterine spread and/or recurrence. The tumors are composed of spindled cells. The main differentials include smooth muscle tumors and endometrial stromal tumors and their morphology may overlap with that of UIMT. Immunohistochemical positivity for ALK or FISH testing for ALK rearrangements can help in the diagnosis.

Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship

Frequently involving an endometrial polyp, minimal uterine serous carcinoma (MUSC) represents the earliest recognizable forms of endometrial serous carcinoma. The aim of this study was to provide a comprehensive morphological and clinical outcome assessment of MUSC involving endometrial polyp. A total of 77 fully staged MUSCs involving endometrial polyp were identified, including 53 MUSCs confined to polyp and 24 nonpolyp confined tumors. Extrauterine disease was found in 17% (9/53) of polyp-confined MUSCs compared to 41.7% (10/24) of nonpolyp confined tumors (p=0.02). Lymphovascular invasion was observed in 3.8% (2/53) of polyp-confined cases compared to 25% (6/24) of nonpolyp confined cases (p=0.047). Lymph node metastasis was observed in 11.3% (6/53) of polyp-confined cases, compared to 29.2% (7/24) of nonpolyp confined cases (p=0.058). Positive pelvic washing cytology was seen in 18.9% (10/53) of polyp-confined versus 37.5% (9/24) of nonpolyp confined tumors (p=0.078). Overall, 58 of 77 (75.3%) patients had low tumor stage (57 stage I cases and 1 stage II case) and only two patients (3.5%) had a recurrence. In contrast, 19 of 77 (24.7%) patients had advanced stage (stage III or IV) disease and 17 (89.5%) patients had recurrence (p<0.0001). Only one of 57 low-stage patient (1.7%) versus11 of 19 high-stage patients (57.8%) died of the tumor (p<0.0001). Five of 53 (9.4%) patients with polyp-confined MUSC and 7 of 24 (29.2%) patients with nonpolyp confined MUSC died of the disease (p=0.03). In conclusion, while a small percentage of MUSCs exist without the involvement of an endometrial polyp, a close topographic relationship between MUSC and the endometrial polyp is confirmed in this largest series, supporting the theory that most if not all MUSCs arise in an EMP. Patients with MUSC without extrauterine spread have an excellent prognosis. Compared to patients with MUSC confined to an endometrial polyp, patients with MUSC extending to the background endometrium have a significantly higher risk for high-stage disease at presentation.

Relationship between CA-125 Levels and Extrauterine Spread in Endometrial Cancer Endometrioid Type at Dr. Soetomo General Hospital Surabaya

Background: Endometrial cancer is the sixth most common malignancy incidence in women worldwide. The surgical staging in endometrial cancer management such as bilateral salpingooophorectomy and lymphadenectomy is not a routine procedure for all endometrial cancer patients. Therefore, a biomarker to estimate the presence of endometrial cancer metastases to adnexa and lymph nodes is needed. This study aims to find out the level of cancer antigen 125 (CA-125) in endometrial cancer endometrioid type and the relationship between the level of CA-125 and the incidence of adnexal metastases, lymph node metastases, clinical stage, and myometrial invasion.Methods: This observational analytic study used a direct observational design. The in-vitro quantitative examination was performed to measure CA-125 levels using CA-125 Advia Centaur CA-125 Kit. Fischer exact test used to analyzed CA-125 levels with the subject characteristics. All the statistical analyses were performed using SPSS v. 21.0.Results: Of the 30 research subjects with the characteristics of the most age groups of 51–60 years (60%), with the most multiparous parity (73.3%), grade III (43.3%), myometrial invasion &gt; 50% by 66.7%, early-stage (63.3%), the incidence of adnexal metastases (30%), and the incidence of lymph node (LN) metastases (10%), a significant relationship between CA-125 levels and lymph node (LN) metastases was found with a p = 0.041 and the phi association of 0.016 and between CA-125 levels and adnexal metastases with a p = 0.035 and the phi association of 0.026. There was also a significant relationship between CA-125 levels and the clinical stage (advanced stage) with p = 0.004 and the phi association of 0.002. There is no significant relationship with a p = 0.702 and a phi association value of -0.098.Conclusions: CA-125 can be used as a tumor marker to predict the presence of extrauterine metastases (adnexa &amp; lymph nodes).