History Of Endometrial Cancer Research Articles

6634 Dual-Mediated PTH And Osteolytic Hypercalcemia In Metastatic Endometrial Carcinoma

Abstract Disclosure: C.K. Persaud: None. D.J. Beckman: None. Background: Hypercalcemia of malignancy occurs in 20-30% of advanced stage cancer patients. Etiologies include parathyroid hormone-related peptides (PTHrP)-mediated, osteolytic metastases-mediated, overproduction of 1,25-dihydroxycholecalciferol, and rarely parathyroid hormone (PTH)-mediated. PTH-mediated hypercalcemia of malignancy is rare and occurs through ectopic PTH production or primary hyperparathyroidism. We report a rare case of both PTH-mediated and osteolytic-mediated hypercalcemia in the setting of malignancy. Clinical Case: A 57-year-old female with history of endometrial cancer and multiple solid organ metastasis, presented with two weeks of progressive poor oral intake, nausea, emesis, and right flank pain. On hospital admission, she had a serum calcium of >20.1 mg/dL (8.6-10.2), PTH of 203 pg/mL (15.0-65.0), and creatinine of 1.7 mg/dL (0.7-1.2, baseline 1.3). Non-contrasted CT chest/abdomen/pelvis noted increased size of known right adrenal metastasis, new left adrenal metastasis, periaortic lymphadenopathy, and scattered nodules in the subcutaneous tissues of the abdomen and chest, however bone metastasis were not noted. Patient’s hypercalcemia was treated with zoledronic acid, calcitonin, cinacalcet, and eventually denosumab due to difficulty controlling hypercalcemia. Additional labs obtained during evaluation included ionized calcium >2.5 nmol/L (1.12-1.32), PTHrP <2.0 pmol/L (<2.0), 1,25-dihydroxycholecalciferol <10 pg/mL (21-65). Patient’s right adrenal metastasis biopsy one month prior to admission was subsequently stained for PTH and was negative. Technetium-99m sestamibi scan was obtained for localization of parathyroid adenoma or carcinoma. The scan did not localize, however did show numerous new lytic lesions in the skull, spine, sternum, rib cage, and right humerus. Patient’s hospital course was complicated by progressively worsening renal function, anemia, and thrombocytopenia. Patient was discharged to a long-term acute rehab facility off hypercalcemia treatment with a corrected calcium of 10.0 mg/dL. Conclusion: PTH-mediated hypercalcemia is a rare cause of hypercalcemia of malignancy. PTH levels are typically low or low-normal in osteolytic mediated hypercalcemia. Generally, if PTH is elevated in hypercalcemia, an alternate etiology is not evaluated. This case highlights a rare dual-mediated hypercalcemia of malignancy. The patient’s PTH level elevation was discordant with her high degree of hypercalcemia and prolonged treatment course. She was subsequently found to have widespread bone metastases contributing to hypercalcemia. While multiple etiologies of hypercalcemia can be rare, it is important to evaluate for all contributing causes, especially with additional clinical conditions, such as malignancy. Presentation: 6/3/2024

Predicting risk of endometrial cancer in asymptomatic women (PRECISION): Model development and external validation.

Develop an endometrial cancer risk prediction model and externally validate it for UK primary care use. Cohort study. The UK Biobank was used for model development and a linked primary (Clinical Practice Research Datalink, CPRD) and secondary care (HES), mortality (ONS) and cancer register (NRCAS) dataset was used for external validation. Women aged 45-60 years with no history of endometrial cancer or hysterectomy. Model development was performed using a flexible parametric survival model and stepwise backward selection aiming to minimise the Akaike information criterion. Model performance on external validation was assessed through flexible calibration plots, calculation of the expected to observed ratio and C-statistic and decision curve analysis. Endometrial cancer diagnosis within 1-10 years of the index date. Model development included 222 031 women (902 incident endometrial cancer cases) and external validation 3 094 371 women (8585 endometrial cancer cases). The final model (with equation provided) incorporated age, body mass index, waist circumference, age at menarche, menopause and last birth, hormone replacement, tamoxifen and oral contraceptive pill use, type 2 diabetes, smoking and family history of bowel cancer. It was well calibrated on external validation (calibration slope 1.14, 95% confidence interval [CI] 1.11-1.17, E/O 1.03, 95% CI 1.01-1.05), with moderate/good discrimination (C-statistic 0.70, 95% CI 0.69-0.70) and had improved net benefit compared with previously developed models. The Predicting risk of endometrial cancer in asymptomatic women model (PRECISION), using easily measurable anthropometric, reproductive, personal and family history, accurately quantifies a woman's 10-year risk of endometrial cancer. Its use could determine eligibility for primary endometrial cancer prevention trials and for targeted resource allocation in UK general practices.

Endometrial thickness is a prognostic factor in endometrial carcinoma

Background: Ultrasonography is a method that is commonly used today to measure endometrial thickness. It is useful as the initial step to detect endometrial hyperplasia or cancer in women with abnormal uterine bleeding. This study seeks to explore the predictive role of endometrial thickness in the development of endometrial cancer and identify the variables that affect endometrial thickness. Methods: This study is a cross sectional retrospective analytical study of women with a history of endometrial cancer who underwent transabdominal ultrasonography or transvaginal ultrasonography (TVS) followed by complete surgical staging between January 2019 and December 2021 at Dr. Kariadi General Hospital Semarang. Patients were categorized by endometrial thickness into ≤8 mm and >8 mm. In order to compare the endometrial thickness and clinicopathology traits, a bivariate analysis was done. The study proceeded with multivariate analysis and logistic regression if more than one bivariate analysis revealed a significant correlation (p<0.25). Results: This study involved 55 participants who had endometrial thickness measurements taken. Endometrial thickness was used to divide the patient population into two groups: ≤8 mm (n=28) and >8 mm (n=27). Tumor differentiation grading showed a significant difference between the two groups (p<0.001). The thickness of the endometrium is a significant prognostic of endometrial carcinoma based on the degree of tumor differentiation (p<0.001). With each millimeter increase in the endometrium, the likelihood of endometrial carcinoma increases significantly by 1,25 [p<0.001; 95%CI =1.112-1.404] times. Conclusion: As a result, the degree of tumor differentiation on post-operative histological analysis is correlated with the thickness of the endometrium. The endometrium's thickness considerably increased as the tumor differentiation level deteriorated. These findings highlight the significance of endometrial thickness as a possible predictor of tumor differentiation and prognosis in endometrial cancer.

Risk of adverse obstetric outcomes in patients with a history of endometrial cancer: A nationwide population-based cohort study.

To evaluate adverse obstetric outcomes in women with a history of endometrial cancer (EC). Population-based cohort study. The Korean National Health Insurance (KNHI) claims database. Women who gave birth between 2009 and 2016, with a history of EC prior to pregnancy. The KNHI database was used to compare obstetric outcomes of women with and without a history of EC, using the ICD-10 codes. Multivariable logistic regression models were used to determine the associations between a history of EC and adverse obstetric outcomes. Adverse obstetric outcomes. Overall, 248 and 3 335 359 women with and without a history of EC, respectively, gave birth. When adjusted for age, primiparity and comorbidities, an increased risk of multiple gestations (odds ratio [OR] 4.925, 95% confidence interval [CI] 3.394-7.147), caesarean delivery (OR 2.005, 95% CI 1.535-2.62) and preterm birth (OR 1.941, 95% CI 1.107-3.404) was observed among women with a history of EC. We were unable to demonstrate significant differences in the risk of pre-eclampsia, gestational diabetes, vacuum delivery, placenta praevia, placenta accreta spectrum, placental abruption and postpartum haemorrhage between the groups. In the sensitivity analyses excluding multiple gestations, an increased risk of preterm birth was not observed among women with a history of EC (OR 1.276, 95% CI 0.565-2.881). There is no convincing evidence of an increased risk of adverse obstetric outcomes among women with a history of EC. Our findings would be useful in counselling of patients with EC who are undergoing fertility-sparing treatment.

Abstract OT2-01-10: WinPro: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early-stage hormone receptor-positive breast cancer

Abstract WinPro: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early-stage hormone receptor-positive breast cancer Authors Teesha Downton1,2,3, Davendra Segara3, Andrew Ong4, Janne Bingham5, Emma-Kate Carson4, Julia Chen1,2,3, Kate Middleton3, Geoffrey Lindeman6, Andrew Parker3, Elgene Lim1,2,3. Affiliations 1Garvan Institute of Medical Research, Darlinghurst NSW, Australia; 2School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales Sydney, Australia; 3St Vincent’s Hospital Sydney, Darlinghurst NSW, Australia; 4Campbelltown Hospital, Campbelltown NSW, Australia; 5Royal Adelaide Hospital, Adelaide SA, Australia; 6Walter & Eliza Hall Institute of Medical Research, Parkville VIC, Australia Disclosures T. Downton: None. D. Segara: None. A. Ong: None. J. Bingham: None. E. Carson: None. J. Chen: None. K. Middleton: None. G. Lindeman: None. A. Parker: None. E. Lim: Advisory Board for Pfizer, Astra Zeneca, Lilly, Roche, Novartis, Gilead Australia. Research Funding from Pfizer, Novartis, Bayer. Abstract Background: Preclinical studies have observed that progesterone has inhibitory effects on the estrogen-stimulated growth of estrogen receptor (ER)-positive, progesterone receptor (PR)-positive breast cancer. Mohammed H et al. (Nature 2015) identified that activated PR associates with the ER and modulates the interactions of the ER with chromatin, with a shift towards the transcription of genes associated with apoptosis and differentiation, and away from genes associated with proliferation. We hypothesize that the addition of prometrium, a microionized progesterone, may enhance the anti-proliferative effects of standard endocrine therapy in women with ER-positive PR-positive breast cancer. Trial Design: WinPro (NCT03906669) is an ongoing multicenter, phase II, randomized, open-label, window of opportunity study comparing the effect on standard endocrine therapy with or without prometrium on breast cancer cell proliferation. The study population is postmenopausal women with early-stage operable breast cancer where the tumor is ≥5mm on imaging, ER ≥10%, PR≥10%, and HER2-negative. Patients currently on hormone replacement therapy or the oral contraceptive pill, or who have a history of endometrial cancer or venous thromboembolism are not eligible. Patients are randomized 1:1:1 to letrozole 2.5mg daily, letrozole 2.5mg + prometrium 300mg daily, or tamoxifen 20mg + prometrium 300mg daily. Allocated treatment is taken for 14 days prior to surgery. Primary surgery and adjuvant treatment is as per standard of care. Objectives: The primary objective is to compare the geometric mean suppression of centrally assessed Ki67 between the diagnostic biopsy sample (pre-treatment) and the surgical sample (post-treatment). The secondary objective is to evaluate safety and tolerability. Tertiary objectives include defining genes predictive of a reduction in Ki67, and evaluating the changes in ER, PR, AR, FoxA1, Cyclin D1, and apoptotic markers in breast tumors post-intervention. Accrual: This study opened in February 2018 and as of 13 July 2022, 164 patients have been enrolled. Target accrual is 200 patients. Contact information: This study is led at St Vincent’s Hospital Sydney, Australia, and funded by the Cancer Council of NSW and the NHMRC Translational Breast Cancer Project grant. Contact: Elgene Lim MBBS FRACP PhD at e.lim@garvan.org.au. Citation Format: Teesha Downton, Davendra Segara, Andrew Ong, Janne Bingham, Emma-Kate Carson, Julia Chen, Kate Middleton, Geoffrey Lindeman, Andrew Parker, Elgene Lim. WinPro: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early-stage hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-10.

Clinicopathological characteristics and possible risk factors for extrauterine metastases in endometrial carcinoma

Introduction: Extrauterine metastases often occur in patients with advanced stages of endometrial carcinoma. Retroperitoneal lymph nodes and pelvic lymph nodes are the most common metastatic sites for endometrial carcinoma, while distant metastases, including those to the lung, liver, and brain, are uncommon. This study compares the characteristics of endometrial carcinoma with or without extrauterine metastases and evaluates risk factors associated with extrauterine metastases.
 Methods: A retrospective analytical study of 155 women with a history of endometrial cancer
 following complete surgical staging treatment from January 2017 to December 2021 at Dr. Kariadi General Hospital Semarang. All data were obtained using medical records. The clinical and pathological characteristics were compared using the Unpaired T-test and Chi-Square test. Multivariate logistic models were performed to estimate the odds ratio (OR) and 95% CI to analyze independent risk factors for extrauterine metastases.
 Results A total of 155 endometrial cancer patients were included in this study. Of these, 77 patients have extrauterine metastases (49.67%). The most common site for extrauterine metastases is ovarian metastases (26.5%). Using univariable and bivariate analysis, tumor differentiation grading (OR=3.69, p=0.027) and myometrial invasion (OR=2.84, p=0.027) were the two risk factors associated with extrauterine metastases. 
 Conclusion: There were significant differences in clinicopathological characteristics between the two groups with and without extrauterine metastases. Tumor differentiation grading and myometrial invasion were two independent risk factors.

S2694 An Uncommon Cause of Upper Gastrointestinal Bleeding

Introduction: We present a case of GI bleeding due to a direct communication between a pancreatic fistula and the splenic vein. Case Description/Methods: A 55 year-old female with a history of endometrial cancer, superficial lower extremity thrombus, and alcohol use presented with abdominal pain and dark red blood in her stools requiring blood transfusion. She reported recent ibuprofen use. An upper endoscopy showed small esophageal varices without red wales or stigmata of recent hemorrhage. A CT demonstrated extensive subacute thrombosis of the right and left portal veins, main portal vein (PV), proximal superior mesenteric vein (SMV) and splenic vein (SV). The pancreas appeared atrophic and contained small cysts. There was small ascites. Liver biopsy demonstrated mild steatohepatitis without fibrosis. She underwent placement of a transjugular intrahepatic portosystemic shunt (TIPS) with thrombectomy from the PV, SMV, and SV and was started on anticoagulation. Due to bleeding recurrence, she underwent TIPS revision with tPA injection and additional mechanical thrombectomy. Subsequently on an ultrasound, TIPS thrombosis was again noted and during TIPS revision, a communication was noted between the pancreatic duct and splenic vein, finally identifying the likely source of bleeding. A splenic vein stent was placed. Discussion: This case highlights an uncommon cause of upper GI bleeding and reinforces the importance of keeping a broad differential diagnosis for a patient with portal hypertension. Our patient had a complicated course with 2 TIPS revisions and esophageal varices, but the source of her bleeding was neither variceal nor mucosal. (Figure) Splenic vein thrombus can result as a complication of pancreatitis and subsequently lead to “sinestrial” (left-sided) portal hypertension and the formation of gastric varices which can also present with gastrointestinal bleed (GIB). Our patient did not have the classic finding of sinestral portal hypertension associated with SV thrombosis: gastric varices. Furthermore, during her initial TIPS placement and even her initial thrombectomy, no pancreatic fistula was observed. Although not always visualized due to the intermittent nature of bleeding, hemosuccus pancreaticus in the setting of chronic alcoholic pancreatitis most commonly involves the splenic artery (60-65%) and less commonly involves the gastroduodenal artery. Our patient’s case is unusual because angiogram demonstrated direct communication between a pancreatic fistula and the splenic vein, not the splenic artery.Figure 1.: Large clot burden at superior mesenteric vein.

A geospatial analysis of healthy food resource access to combat obesity in endometrial cancer survivors living in the deep south: Is it equitable?

e18507 Background: Obesity is a known risk factor for primary endometrial cancer. Several reports demonstrate a higher rate of mortality and shortened life span in obese patients with endometrial cancer, attributable at least in part to obesity-related comorbidities. This study examined endometrial cancer survivors’ access to healthy food resources recommended by ASCO and the Commission on Cancer (CoC) survivorship guidelines to combat obesity. Methods: Participants included women seen between 2015 – 2020 at an academic medical center in the Deep South for treatment of endometrial cancer who lived in South Carolina. Demographic and comorbidity data were abstracted from medical records. A socioeconomic status (SES) score (SES-1 = low, SES 5 = high) was generated for each patient using census block-group-level data. Food desert data were obtained from the United States Department of Agriculture (USDA). A social vulnerability index (SVI) was assigned to each patient using data from the Center for Disease Control and Prevention (CDC) to evaluate the negative effects of neighborhood external stresses on human health. SVI is a composite of 15 factors including socioeconomic status, household composition and disability, and minority status and language. Food resources were obtained from a publicly available database. Geospatial techniques assessed patient geospatial access (driving distance, i.e., recommended resource access of ̃½-mile radius in an urban area, 10-mile radius in a rural area around a patient’s home) to healthy food resources in relation to patient’s sociodemographic characteristics. Results: Of the 712 endometrial cancer survivors included in the analysis, 23% identified as African American and 29% lived in the lowest SES census block-groups (SES-1 and SES-2). More than half of the patients had low grade cancer; more than two-thirds had Stage I or Stage II disease. The mean BMI for African Americans was 41 and 37 for Caucasian Americans. Forty percent of survivors lived in a food desert. Survivors living in a food desert with low SES (SES-1 and SES-2) had significantly higher social vulnerability (p = 0.0001), higher poverty rates (p = 0.0001), and lower median income (p = 0.0001). The average driving distance was 0.1 miles (range 0.017 – 12.0 miles) with those in lower SES (SES-1 and SES-2) and those living in a food desert driving further (p = 0.05). Conclusions: Obesity rates were high among endometrial cancer patients living in the Deep South. Endometrial cancer survivors with higher social vulnerability and lower income were more likely to live in food deserts. Oncologic providers of survivorship care must understand healthy food resource access and patient SES to help women with a history of endometrial cancer fulfill ASCO and CoC recommended guidelines targeting obesity. Survivorship programs should be focused on meeting these social needs for holistic care.

Falls, walking or balance problems, and limitations in activities of daily living (ADLs) among older endometrial cancer survivors.

Functional status deficits are important quality of life concerns for older cancer survivors. We examined the prevalence of falls, walking/balance problems, and limitations in activities of daily living (ADLs) among older women with a history of endometrial cancer. Cancer registry records from the Surveillance, Epidemiology, and End Results (SEER) program linked with Medicare Health Outcomes Survey (MHOS) data were used to identify endometrial cancer survivors aged ≥ 65years who completed a survey ≥ 1year after their cancer diagnosis (N = 3766), as well as an age- and race-matched group of women without a cancer history (N = 3766). We estimated prevalence ratios (PRs) to compare the prevalence of falls, walking or balance problems, and limitations in ADLs (bathing, dressing, eating, getting in/out of chairs, walking, using the toilet) between groups. Difficulty with walking or balance was more common among survivors than the noncancer group (43% vs 36%; PR = 1.19; 95% CI: 1.10-1.27). Fall prevalence was similar between groups (endometrial cancer: 25%; noncancer: 26%; PR = 0.98; 95% CI: 0.89-1.08). Nearly half of endometrial cancer survivors (47%) reported at least one ADL limitation, with several activities (getting in/out of a chair, walking, bathing, using the toilet) more often limited among survivors than among women without cancer. Functional impairments, especially problems with walking and/or balance, are common among older endometrial cancer survivors. Our results highlight the importance of addressing functional problems during the ongoing survivorship care of women with a history of endometrial cancer, with referral to rehabilitation or other relevant services when indicated.

Retroactive assessment for DNA mismatch repair deficiency in women with a history of endometrial cancer

Objectives. Beginning in 2014, the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists have recommended universal tumor testing for mismatch repair deficiency in endometrial cancer. Mismatch repair testing can triage patients who may benefit from genetic testing for Lynch syndrome. Many women previously diagnosed with endometrial cancer have not undergone mismatch repair tumor testing. We sought to determine the feasibility of retroactive assessment for mismatch repair deficiency among women with diagnosed with endometrial cancer prior to 2014. Methods. Between 2016 and 2018, we identified 36 patients presenting for gynecologic oncology follow-up visits who were previously diagnosed with endometrial cancer. The endometrial pathology underwent tumor assessment for loss of expression of mismatch repair proteins by immunohistochemistry. Patients with abnormal mismatch repair testing were referred to genetic counseling and, if indicated, for germline genetic testing. Results. Thirty-six patients underwent retroactive tumor immunohistochemistry, yielding 10 (28%) abnormal results, including nine (25%) with loss of one or more mismatch repair proteins and one with inconclusive staining (2.8%). All ten patients with abnormal immunohistochemistry were referred to genetic counseling; 9 (90%) accepted the referral and proceeded with genetic testing. One pathogenic mutation was identified in CHEK2 (11%). Five patients (56%) were found to have a variant of unknown significance. Conclusions. Implementation of universal retroactive tumor testing for mismatch repair deficiency in patients previously diagnosed with endometrial cancer is feasible. With the growing use of new molecular classification protocols for endometrial tumors, identification of mismatch repair deficiency may have significant clinicopathologic implications.

Concomitant Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Discovered by Flow Cytometry

Abstract Casestudy: Chronic lymphocytic leukemia (CLL) accounts for about 30% of all lymphoid neoplasms and is the most common adult blood cancer in the Western world. Mantle cell lymphoma (MCL) accounts for only about 6% of all B-cell lymphomas in Western countries. MCL and CLL are both CD5 positive B-cell lymphoproliferative disorders. It is necessary to distinguish these two entities as MCL is a more aggressive disease, and requires specific treatment. MCL and CLL can occur in one patient at the same time and is often termed a composite lymphoma. We present an 84-year-old female with a history of endometrial cancer who was found to have splenomegaly and lymphadenopathy. Flow cytometry was performed upon her peripheral blood specimen which demonstrated two distinct populations of abnormal light chain restricted B-cell populations. One population demonstrated kappa light chain restriction and was positive for CD45, CD19, CD20, CD5, CD38, FMC-7, and CD22, representing MCL. The other population showed dim lambda light chain restriction that was also positive for CD45, CD19, dim CD20, CD5, and CD23, representing CLL. FISH studies demonstrated t(11;14), and four common deletions or chromosome aneuploidy associated with CLL. These findings confirmed the dual populations of CLL and MCL. This is an interesting case because it is a very rare combination with only a few cases having been reported with two distinct cell populations in one patient at the same time.

Concomitant Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Discovered by Flow Cytometry

Abstract Casestudy: Chronic lymphocytic leukemia (CLL) accounts for about 30% of all lymphoid neoplasms and is the most common adult blood cancer in the Western world. Mantle cell lymphoma (MCL) accounts for only about 6% of all B-cell lymphomas in Western countries. MCL and CLL are both CD5 positive B-cell lymphoproliferative disorders. It is necessary to distinguish these two entities as MCL is a more aggressive disease, and requires specific treatment. MCL and CLL can occur in one patient at the same time and is often termed a composite lymphoma. We present an 84-year-old female with a history of endometrial cancer who was found to have splenomegaly and lymphadenopathy. Flow cytometry was performed upon her peripheral blood specimen which demonstrated two distinct populations of abnormal light chain restricted B-cell populations. One population demonstrated kappa light chain restriction and was positive for CD45, CD19, CD20, CD5, CD38, FMC-7, and CD22, representing MCL. The other population showed dim lambda light chain restriction that was also positive for CD45, CD19, dim CD20, CD5, and CD23, representing CLL. FISH studies demonstrated t(11;14), and four common deletions or chromosome aneuploidy associated with CLL. These findings confirmed the dual populations of CLL and MCL. This is an interesting case because it is a very rare combination with only a few cases having been reported with two distinct cell populations in one patient at the same time.

Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome

There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a BRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic BRCA2 variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer.

A single-arm clinical trial investigating the effectiveness of a non-hormonal, hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors

ObjectiveTo assess the efficacy of non-hormonal, hyaluronic acid (HLA)-based vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in women with a history of endometrial cancer. MethodsFor this single-arm, prospective, longitudinal trial, we enrolled disease-free women with a history of endometrial cancer who underwent surgery (total hysterectomy) and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12–14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1]; 4–6 weeks [T2]; 12–14 weeks [T3]; 22–24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). ResultsOf 43 patients, mean age was 59 years (range, 38–78); 54% (23/43) were partnered; and 49% (21/43) were sexually active. VAS, VuAS, MSCL, and SAQ (Sexual Activity Questionnaire) scores significantly improved from baseline to each assessment point (all p < .002). FSFI total mean scores significantly increased from T1 to T2 (p < .05) and from T1 to T4 (p < .03). At T1, 41% (16/39) felt confident about future sexual activity compared to 68% (17/25) at T4 (p = .096). Severely elevated vaginal pH (>6.5) decreased from 30% (13/43) at T1 to 19% (5/26) at T4 (p = .41). ConclusionThe HLA-based gel improved vulvovaginal health and sexual function of endometrial cancer survivors in perceived symptoms and clinical exam outcomes. HLA administration 1–2×/week is recommended for women in natural menopause; a 3–5×/week schedule appears more effective for symptom relief in cancer survivors.

3045 An Unusual Episode of Acute Diverticulitis Despite Concurrent Antibiotic Therapy

INTRODUCTION: Diverticulosis occurs when weak spots in the outer layer of colonic muscle weaken giving way to an inner layer of protruding pouches. The progression to diverticulitis occurs when these protruding pouches become inflamed and infected which may ultimately progress to systemic symptoms that include fever, pain, malaise, constipation and vomiting. It is estimated that 50% of the population develops diverticulosis by age 50 and 65% by age 80. Additionally, an estimated 15-20% of the population with diverticulosis will go on to develop diverticulitis. Mild cases of diverticulitis are treated with oral antibiotics and a liquid diet whereas severe cases are treated with IV antibiotics and bowel rest. Here, we present a case of a diverticulitis episode that developed while a patient was already being treated with antibiotics. CASE DESCRIPTION/METHODS: A 64 year old female with a history of endometrial cancer who presented to the hospital for one day history of abdominal pain associated with loose bowel movements. She stated she has had loose bowel movements since starting H. pylori antibiotics that included amoxicillin and clarithromycin 2 weeks prior to presentation. She had an esophagoduodenoscopy 3 months prior that revealed chronic gastritis without dysplasia as well as biopsy proven H. pylori. Her colonoscopy at the same time showed internal hemorrhoids and a single hyperplastic polyp. Her vital signs were unremarkable and she was afebrile. Her white blood cell count on presentation was 13.9. She had a CT scan of the abdomen and pelvis that revealed acute sigmoid diverticulitis and cholelithiasis without evidence of acute cholecystitis. She was subsequently admitted to the hospital and treated with rocephin and flagyl as well as bowel rest. Blood cultures, stool cultures and clostridium difficile cultures were negative. Patient recovered over the next couple of days with resolution of her symptoms and her WBC count. DISCUSSION: This purpose of this case is to highlight the current management and treatment options for diverticulitis. Current guidelines recommend antibiotics and bowel rest during acute episodes of diverticulitis. However, this case represents an unusual scenario where a patient develops acute diverticulitis despite concurrent treatment with antibiotics for ongoing H. pylori infection. Further randomized-controlled trials may help delineate treatment modalities for acute diverticulitis as current treatment guidelines may result in breakthrough diverticulitis episodes.

Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a service setting.

Muir-Torre syndrome (MTS) is a subtype of Lynch syndrome, which encompasses the combination of sebaceous skin tumours or keratoacanthomas and internal malignancy, due to mutations in DNA mismatch repair genes. Sebaceous neoplasms (SNs) may occur before other malignancies, and may lead to the diagnosis, which allows testing of other family members, cancer surveillance, risk-reducing surgery or prevention therapies. To evaluate the efficacy of universal immunohistochemistry (IHC) screening of SNs in a service setting. Patients with SNs were ascertained by a regional clinical pathology service over a 3-year period. Results of tumour IHC, clinical genetics notes and germline genetic testing were retrospectively reviewed. In total, 62 patients presented with 71 SNs; 9 (15%) of these patients had previously diagnosed MTS. Tumour IHC was performed for 50 of the 53 remaining patients (94%); 26 (52%) had loss of staining of one or more mismatch repair proteins. Fifteen patients were referred to the Clinical Genetics department, and 10 patients underwent germline genetic testing. Two had a new diagnosis of MTS confirmed, with heterozygous pathogenic mutations detected in the MSH2 and PMS2 genes (diagnostic yield 20%). The PMS2 mutation was identified in a 57-year-old woman with a sebaceous adenoma and history of endometrial cancer; to our knowledge, this is the first time a PMS2 mutation has been reported in MTS. Universal IHC screening of SNs is an effective method to identify cases for further genetic evaluation. Rates of referral to clinical genetics were only moderate (58%). Increased awareness of MTS could help improve the rate of onward referral.

Robotic Splenectomy for Isolated Splenic Recurrence of Endometrial Adenocarcinoma

Study ObjectiveTo demonstrate management of a rare case of an isolated intraparenchymal splenic metastasis of endometrial cancer with robotic-assisted surgery. DesignCase report (Canadian Task Force Classification III). SettingA 55-year-old patient with a history of endometrial cancer was found to have a splenic lesion on a follow-up examination. She underwent surgical staging, involving total hysterectomy, bilateral salpingo-oopherectomy, pelvic lymphadenectomy, and peritoneal washing, in 2014, and the final pathological findings showed an endometrioid endometrial adenocarcinoma, International Federation of Gynecology and Obstetrics stage IB G2. Multidisciplinary counseling was provided, and the patient opted for strict medical surveillance. At 20 months after the primary treatment, the patient experienced a vaginal cuff recurrence and refused radiation therapy. She instead underwent robotic surgery, followed by 6 cycles of carboplatin 6 AUC and paclitaxel 175 mg/m2. Seventeen months later, a positron emission tomography/computed tomography scan revealed a 3-cm intraparenchymal lesion of the spleen, and robotic splenectomy was scheduled. The Institutional Review Board approved this study. InterventionThe operative time was 90 minutes, and blood loss was <50 mL. The operation was performed successfully, with no intraoperative and postoperative complications. Histopathological analysis showed a 3-cm intraparenchymal splenic lesion. The patient was discharged on day +2, and 46 days later started adjuvant chemotherapy based on carboplatin 6 AUC and doxorubicin (Caelyx) 30 mg/m2. At a 2-month follow-up, the patient was disease-free and in good general condition. ConclusionThis case demonstrates the successful robotic management of recurrent endometrial cancer.

Molecular Screening for Lynch Syndrome in Young Patients With Colorectal Adenomas

BackgroundThe frequency of mismatch repair (MMR) deficiency (dMMR) in patients < 50 years with adenomas without a known germline mutation is unknown. Our aim was to define the frequency of dMMRs in adenomas from patients aged < 50 years. Patients and MethodsWe identified all patients aged 18 to 49 years who had undergone colonoscopy at Memorial Sloan Kettering Cancer Center from 2008 to 2013 and were identified as having tubular, villous, or tubulovillous adenomas on pathology. Patients with a personal history of colorectal cancer, polyposis syndrome, or inflammatory bowel disease before colonoscopy were excluded. Age, demographic data, family history of cancer, personal history of cancer, use of radiation, reason for colonoscopy, and colonoscopy findings were recorded. Polyps were stained using immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 proteins. ResultsA total of 208 patients with 266 polyps were identified. Of the 266 polyps, 259 could be stained. Of the 208 patients, 82 (40%) were men; their mean age was 44 years. The indication for colonoscopy was screening for 120, diagnostic for 75, and therapeutic for 15. Of the 259 examined polyps, 246 (95%) were tubular adenomas and 13 were tubulovillous adenomas (5%). One patient (0.4%) was found to have dMMRs in 1 polyp. This patient was a 42-year-old woman with a history of endometrial cancer who had undergone colonoscopy for hematochezia. A 15-mm transverse tubular adenoma was found that was deficient in MLH1 and PMS2. ConclusionOur results indicate that routine screening of polyps in patients aged < 50 years old is not an effective tool for identifying Lynch syndrome carriers.

Endometriosis Under Estradiol Stimulation Imaged Using 18F-FDG and Its Control After Estradiol Cessation and Progesterone Hormonal Replacement.

Endometriosis is a frequent and benign cause of disabling abdominal pain, for which a diagnosis suspicion is clinically raised, but its confirmation necessitates a surgical exploration by laparoscopy. Foci of endometriosis proliferate under estrogen stimulation, like normal endometrium. We present a patient under estradiol stimulation for a history of endometrial cancer who underwent a PET/CT scan to assess an abdominal lesion showing a high F-FDG uptake, which normalized under progesterone hormonal replacement and cessation of estradiol. Two consecutive biopsies confirmed endometriosis. F-FDG evaluation of endometriosis under estrogen stimulation could be a promising approach to refractory endometriosis assessment.

Improving Quality and Decreasing Cost in Gynecologic Oncology Care. Society of Gynecologic Oncology Recommendations for Clinical Practice

Abstract Objective To identify potential cost savings in gynecologic oncology care without sacrificing quality. Methods Members of the Clinical Practice Committee of the Society of Gynecologic Oncology were asked to review current practice patterns in gynecologic oncology and assess the potential for cost savings founded on evidence-based medicine and current guidelines. Results Five clinical practices were identified including the following: vaginal cytology for endometrial cancer survivors; colposcopy for low grade cytologic abnormalities for cervical cancer survivors; routine imaging studies for gynecologic cancer survivors; screening for ovarian cancer with serum biomarkers and ultrasound; and improving palliative care for gynecologic cancer patients. Review of the published literature and guidelines were performed to make evidence-based recommendations for cost effective quality gynecologic oncology care. Recommendations •Do not perform Pap tests of the vaginal cuff in patients with a history of endometrial cancer. •Do not perform colposcopy for low grade Pap tests in women with a history of cervical cancer. •Avoid routine imaging for cancer surveillance in asymptomatic women with gynecologic cancer, specifically ovarian, endometrial, cervical, vulvar and vaginal cancer. •Do not screen women at low risk for ovarian cancer with ultrasound or CA-125 or other biomarkers. •Do not delay basic level palliative care for women with advanced or relapsed gynecologic cancer, do refer to a palliative care specialist when needed, and avoid unnecessary treatments at life's end.