Publications by authors named "Emily K Hill"

15 Publications

  • Page 1 of 1

A Surgical Window Trial Evaluating Medroxyprogesterone Acetate with or without Entinostat in Patients with Endometrial Cancer and Validation of Biomarkers of Cellular Response.

Clin Cancer Res 2021 Mar 25. Epub 2021 Mar 25.

Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

Purpose: This surgical window of opportunity (window) study assessed the short-term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma.

Patients And Methods: This multisite, randomized, open-label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21-24. Pretreatment and posttreatment tissue was assessed for PR H-scores, Ki-67 levels, and histologic response.

Results: Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H-scores were significantly lower than pretreatment H-scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively, = 0.87). Decreased Ki-67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone ( = 0.13). Median PR H-score decreases were larger when Ki-67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki-67 nuclear staining, consistent with reduced cellular proliferation ( < 0.008).

Conclusions: This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki-67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short-term study, lessons learned can inform future window and treatment trials.
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March 2021

Multimodal perioperative pain protocol for gynecologic laparotomy is associated with reduced hospital length of stay.

J Obstet Gynaecol Res 2021 Mar 8;47(3):1082-1089. Epub 2021 Feb 8.

Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.

Objectives: The primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist.

Methods: We compared 52 patients who underwent laparotomy with a gynecologic oncologist at a single institution between 2017 and 2018, after implementation of a multimodal perioperative pain regimen, to a historic cohort of 94 patients (2016-2017). The multimodal pain regimen included pre- and post-operative administration of oral acetaminophen, gabapentin, and celecoxib, in addition to standard narcotics and optional epidural analgesia. Demographic, surgical, and post-operative data were collected.

Results: On multivariable analysis, bowel resection, stage, surgery length, age, and cohort group were retained as significant independent predictors of length of stay. Patients undergoing laparotomy prior to the pain protocol had a length of stay 1.26 times longer than patients during the post-implementation period (p < 0.01). For complex surgical patients, this translated into a reduction in length of hospital stay of 1.73 days. There was a significant reduction in pain scale score on post-operative day zero from 5 to 3 (p = 0.02) and a non-significant overall reduction of post-operative morphine equivalents, with similar adverse outcomes.

Conclusion: Implementation of a multimodal perioperative pain regimen in patients undergoing gynecologic oncology laparotomy was associated with a significant reduction of length of hospital stay and improved patient-perceived pain, even in the absence of a complete Enhanced Recovery After Surgery (ERAS) protocol.
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March 2021

Is the age of cervical cancer diagnosis changing over time?

J Gynecol Obstet Hum Reprod 2020 Dec 11;50(7):102040. Epub 2020 Dec 11.

University of Iowa Hospitals and Clinics, Department of Obstetrics and Gynecology, Iowa City, IA, United States.

Objectives: The objective of this study was to determine if there has been an increase in the age of diagnosis of cervical cancer over time, specifically in the proportion of patients over 65 years old, given decreasing rates of hysterectomy.

Materials And Methods: A retrospective review of a single institution was conducted including cervical cancer patients seen between 1986 and 2016. Data included demographic variables including age of diagnosis, last cervical cancer screening, and cancer information. Cochran-Armitage test was used to assess temporal trends in the proportion of patients diagnosed over 65.

Results: A total of 1,019 patients with cervical cancer were reviewed, of whom 116 were over the age of 65. The age of diagnosis increased by 0.2 years per calendar year, with an average age of diagnosis of 43.7 years old in 1986 versus 49.5 years old in 2016 (p<0.01). The proportion of patients diagnosed with cervical cancer over the age of 65 did not significantly differ over time (17.2 % in 1986 vs. 14.8 % in 2016, p=0.39). 19.0 % of women diagnosed with cervical cancer over the age of 65 developed cancer despite exiting screening appropriately.

Conclusions: In our cohort, the age of diagnosis of cervical cancer increased over time, however, there was no significant difference in the percentage of women diagnosed over the age of 65.
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December 2020

Effect of Obesity on Cervical Cancer Screening and Outcomes.

J Low Genit Tract Dis 2020 Oct;24(4):358-362

Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA.

Objectives: The aims of the study were to identify whether obese women are less appropriately screened for cervical cancer before diagnosis and to explore related cancer outcomes.

Methods: We retrospectively reviewed all cervical cancer patients at a single institution between 1986 and 2016 and collected demographic information including age, cancer stage, body mass index (BMI), screening information, and cancer outcomes. Morbid obesity was defined as BMI of 40 kg/m or greater, obesity as BMI of 30 to less than 40 kg/m, and nonobese as BMI of less than 30 kg/m. χ, Fisher exact, and Wilcoxon rank sum tests were used to compare variables between BMI categories. Cox regression models were used to evaluate recurrence-free survival and overall survival (OS).

Results: A total of 1,080 patients were reviewed, of whom 311 (29.4%) were obese and 107 (10.1%) morbidly obese. A significant association between BMI and cytology screening was evidenced with morbidly obese women having the highest incorrect rate (64.4%), followed by obese (51.5%) and nonobese women (46.0%, p < .01). There was no significant difference in presence of symptoms at presentation (p = .12) or stage (p = .06) between BMI categories. In multivariable analysis of cancer outcomes, higher BMI was associated with worse OS (p < .01) with a hazard ratio of 1.25 (95% CI = 0.92-1.69) for obese women and hazard ratio 2.27 (95% CI = 1.56-3.31) for morbidly obese women relative to normal weight but recurrence-free survival did not differ between BMI groups (p = .07).

Conclusions: Our study strengthens evidence that obese and morbidly obese women have disproportionate inappropriate screening before cervical cancer diagnosis, and morbidly obese women have worse OS than their counterparts.
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October 2020

Updates in Cervical Cancer Treatment.

Emily K Hill

Clin Obstet Gynecol 2020 03;63(1):3-11

Division of Gynecologic Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

Although rates of cervical cancer in the United States have been declining due to vaccination and screening efforts, it remains the fourth most common cancer in women worldwide and is still far from being eradicated, even in developed nations. This review discusses recent developments in cervical cancer treatment and reviews the literature supporting recent practice changes encompassing staging, surgical management, radiation, chemotherapy, targeted agents including immunotherapy, and imaging.
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March 2020

Gender and the Balance of Parenting and Professional Life among Gynecology Subspecialists.

J Minim Invasive Gynecol 2019 Sep - Oct;26(6):1088-1094. Epub 2018 Oct 30.

Division of Gynecologic Oncology (Dr. Hill), University of Iowa Hospitals and Clinics, Iowa City, Iowa, Warren Alpert Medical School of Brown University (Drs. Stuckey and Robison), Providence, Rhode Island, Brigham and Women's Hospital (Dr. Fiascone), Boston, Massachusetts, Division of Research (Dr. Raker), Women & Infants Hospital, Providence, Rhode Island, Department of Quantitative Health Sciences (Dr. Clark), University of Massachusetts Medical School, Worcester, Massachusetts, Department of Obstetrics and Gynecology (Dr. Brown), Hartford Hospital, Hartford, Connecticut, and Norton Cancer Institute (Dr. Gordinier), Louisville, Kentucky.

Study Objective: To compare the parenting and career patterns of female and male gynecology subspecialists.

Design: Cross-sectional survey study (Canadian Task Force classification II-3).

Setting: Survey administered electronically in February 2015 to physician members of the Society of Gynecologic Oncology, the American Society for Reproductive Medicine, and the American Urogynecologic Society.

Participants: All physician members of the 3 national gynecology subspecialty organizations listed above.

Measurements And Main Results: There were 75 questions in 4 domains: demographics, mentoring issues, work-life balance, and caregiving responsibilities. Data were analyzed for survey sampling weights. Six hundred seventy-seven physicians completed the survey, 62% of whom were women (n = 420; 20.2% response rate). Sixty-four percent were aged 36 to 55 years. Eighty-two percent of respondents had at least 1 child, and men had more children than women (42% of men had 3 or more children compared with 20% of women, p <.0001). Thirty-seven percent of women reported that career plans affected the decision to become a parent somewhat or very much compared with 23% of men (p = .0006). Eighty-three percent of women believed career affected the timing of becoming a parent somewhat or very much compared with 48% of men (p <.0001). In addition, 76% of female physicians perceived that having children decreased their academic productivity compared with 54% of male physicians (p <.0001). Most men and women believed having children had no effect or increased their clinical performance (76% and 65%, respectively), but this was significantly lower in women (p = .01).

Conclusion: Female gynecology subspecialists perceive that their career impacted decisions on parenting more frequently than their male counterparts. They were also more likely than men to report that having children had a negative impact on academic and, to a lesser extent, clinical performance. Increased support for combining childbirth and parenting with training and academic careers is needed.
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May 2020

Current and future prospects for nanotechnology in animal production.

J Anim Sci Biotechnol 2017 14;8:26. Epub 2017 Mar 14.

School of Life Science and Engineering, Foshan University, Foshan, Guangdong China.

Nanoparticles have been used as diagnostic and therapeutic agents in the human medical field for quite some time, though their application in veterinary medicine and animal production is still relatively new. Recently, production demands on the livestock industry have been centered around the use of antibiotics as growth promoters due to growing concern over microbial antibiotic resistance. With many countries reporting increased incidences of antibiotic-resistant bacteria, laws and regulations are being updated to end in-feed antibiotic use in the animal production industry. This sets the need for suitable alternatives to be established for inclusion in feed. Many reports have shown evidence that nanoparticles may be good candidates for animal growth promotion and antimicrobials. The current status and advancements of nanotechnological applications in animal production will be the focus of this review and the emerging roles of nanoparticles for nutrient delivery, biocidal agents, and tools in veterinary medicine and reproduction will be discussed. Additionally, influences on meat, egg, and milk quality will be reviewed.
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March 2017

Gender Differences in Scholarly Productivity Within Academic Gynecologic Oncology Departments.

Obstet Gynecol 2015 Dec;126(6):1279-1284

Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa; the Department of Women's Oncology and the Division of Research, Women & Infants Hospital, and Warren Alpert Medical School of Brown University, Providence, Rhode Island; and the Departments of Otolaryngology, Wayne State University, Detroit, Michigan, and Rutgers New Jersey Medical School, Newark, New Jersey.

Objective: To estimate whether there is a gender difference in scholarly productivity among academic gynecologic oncologists.

Methods: In this cross-sectional study, the academic rank and gender of gynecologic oncology faculty in the United States were determined from online residency and fellowship directories and departmental web sites. Each individual's h-index and years of publication were determined from Scopus (a citation database of peer-reviewed literature). The h-index is a quantification of an author's scholarly productivity that combines the number of publications with the number of times the publications have been cited. We generated descriptive statistics and compared rank, gender, and productivity scores.

Results: Five hundred seven academic faculty within 137 U.S. teaching programs were identified. Of these, 215 (42%) were female and 292 (58%) were male. Men had significantly higher median h-indices than women, 16 compared with 8, respectively (P<.001). Women were more likely to be of junior academic rank with 63% of assistant professors being female compared with 20% of full professors. When stratifying h-indices by gender and academic rank, men had significantly higher h-indices at the assistant professor level (7 compared with 5, P<.001); however, this difference disappeared at the higher ranks. Stratifying by the years of active publication, there was no significant difference between genders.

Conclusion: Female gynecologic oncologists at the assistant professor level had lower scholarly productivity than men; however, at higher academic ranks, they equaled their male counterparts. Women were more junior in rank, had published for fewer years, and were underrepresented in leadership positions.

Level Of Evidence: III.
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December 2015

Antitumor Activity of 3-Indolylmethanamines 31B and PS121912.

Anticancer Res 2015 Nov;35(11):6001-7

Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A.

Aim: To investigate the in vivo effects of 3-indolylmethanamines 31B and PS121912 in treating ovarian cancer and leukemia, respectively.

Materials And Methods: Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and western blotting were applied to demonstrate the induction of apoptosis. Xenografted mice were investigated to show the antitumor effects of 3-indolylmethanamines. (13)C-Nuclear magnetic resource (NMR) and western blotting were used to demonstrate inhibition of glucose metabolism.

Results: 31B inhibited ovarian cancer cell proliferation and activated caspase-3, cleaved poly (ADP-ribose) polymerase 1 (PARP1), and phosphorylated mitogen-activated protein kinases (MAPK), JUN N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. 31B reduced ovarian cancer xenograft tumor growth and PS121912 inhibited the growth of HL-60-derived xenografts without any sign of toxicity. Compound 31B inhibited de novo glycolysis and lipogenesis mediated by the reduction of fatty acid synthase and lactate dehydrogenase-A expression.

Conclusion: 3-Indolylmethanamines represent a new class of antitumor agents. We have shown for the first time the in vivo anticancer effects of 3-indolylmethanamines 31B and PS121912.
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November 2015

HE4 (WFDC2) gene overexpression promotes ovarian tumor growth.

Sci Rep 2014 Jan 6;4:3574. Epub 2014 Jan 6.

Molecular Therapeutics Laboratory, Program in Women's Oncology, Women and Infants' Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02903, USA.

Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates. HE4 displayed responses to tumor microenvironment constituents and presented increased expression as well as nuclear translocation upon EGF, VEGF and Insulin treatment and nucleolar localization with Insulin treatment. HE4 interacts with EGFR, IGF1R, and transcription factor HIF1α. Constructs of antisense phosphorothio-oligonucleotides targeting HE4 arrested tumor growth in nude mice. Collectively these findings implicate increased HE4 expression as a molecular factor in ovarian cancer tumorigenesis. Selective targeting directed towards the HE4 protein demonstrates therapeutic benefits for the treatment of ovarian cancer.
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January 2014

Medical therapy of endometrial cancer: current status and promising novel treatments.

Drugs 2012 Mar;72(5):705-13

Department of Obstetrics Gynecology, The Warren Alpert Medical School of Brown University, Women Infants Hospital of Rhode Island, Providence, RI, USA.

While early-stage endometrial cancer is often successfully treated with surgical intervention, treatment of advanced endometrial carcinoma can be difficult and prognosis poor, particularly in the context of metastatic or recurrent disease. Standard chemotherapy agents for both adjuvant first-line treatment (for selected patients deemed at high risk of relapse) and recurrent endometrial cancer include doxorubicin, platinum agents and paclitaxel. Investigational options currently being studied in phase II trials include both combined regimens of standard chemotherapeutic agents versus radiation as well as targeted treatments such as epothilones, mammalian target of rapamycin (mTOR) inhibitors and anti-angiogenic agents. Recent interest in the molecular pathways of carcinogenesis have lead to increased investigation of these novel agents and the hope that they will impact positively on the overall survival of women with endometrial cancer.
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March 2012

Nomogram for predicting 5-year disease-specific mortality after primary surgery for epithelial ovarian cancer.

Gynecol Oncol 2012 Apr 9;125(1):25-30. Epub 2011 Dec 9.

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Objective: To develop a nomogram based on established prognostic factors to predict the probability of 5-year disease-specific mortality after primary surgery for patients with all stages of epithelial ovarian cancer (EOC) and compare the predictive accuracy with the currently used International Federation of Gynecology and Obstetrics (FIGO) staging system.

Methods: Using a prospectively kept database, we identified all patients with EOC who had their primary surgery at our institution between January 1996 and December 2004. Disease-specific mortality was estimated using the Kaplan-Meier method. Twenty-eight clinical and pathologic factors were analyzed. Significant factors on univariate analysis were included in the Cox proportional hazards regression model, which identified factors utilized in the nomogram. The concordance index (CI) was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed.

Results: A total of 478 patients with EOC were included. The most predictive nomogram was constructed using seven variables: age, FIGO stage, residual disease status, preoperative albumin level, histology, family history suggestive of hereditary breast/ovarian cancer (HBOC) syndrome, and American Society of Anesthesiologists (ASA) status. This nomogram was internally validated using bootstrapping and shown to have excellent calibration with a bootstrap-corrected CI of 0.714. The CI for FIGO staging alone was significantly less at 0.62 (P=0.002).

Conclusion: We have developed an all-stage nomogram to predict 5-year disease-specific mortality after primary surgery for epithelial ovarian cancer. This tool is more accurate than FIGO staging and should be useful for patient counseling, clinical trial eligibility, postoperative management, and follow-up.
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April 2012

Assessing gynecologic and breast cancer survivors' sexual health care needs.

Cancer 2011 Jun 23;117(12):2643-51. Epub 2010 Dec 23.

Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois 60637, USA.

Background: The objective of this study was to identify patterns of interest in receiving care for sexual concerns among women who were survivors of gynecologic and breast cancers.

Methods: Survey and medical records data were collected from June 2008 to March 2009 from 261 gynecologic and breast cancer patients. Logistic regression was used to estimate the effect of age and months since treatment on interest in receiving sexual healthcare.

Results: The mean participant age was 55 years (range, 21-88 years). Only 7% of women had recently sought medical help for sexual issues, yet 41.6% were interested in receiving care. Greater than 30% responded that they would be likely to see a physician to address sexual matters, and 35% of all women were willing to be contacted if a formal program was offered. Compared with older women (aged >65 years), younger women (ages 18-47 years) were significantly more likely to report interest in receiving care to address sexual issues (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.14-7.54) and to see a physician to address sexual matters (OR, 4.51; 95% CI, 1.51-13.43), and they were more willing to be contacted for a formal program (adjusted OR [AOR], 5.00; 95% CI, 1.63-15.28). Compared with women who were currently in treatment, women who last received treatment >12 months previously were significantly more interested in receiving care (AOR, 2.02; 95% CI, 1.02-4.01) and were more willing to be contacted (AOR, 2.49; 95% CI, 1.18-5.26).

Conclusions: Greater than 40% of survivors expressed interest in receiving sexual healthcare, but few had ever sought such care. The current results indicated that there is an unmet need for attention to sexual concerns among women with gynecologic and breast cancers.
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June 2011

What correlates with the intention to be tested for mild cognitive impairment (MCI) in healthy older adults?

Alzheimer Dis Assoc Disord 2008 Apr-Jun;22(2):144-52

Section of Geriatrics, University of Chicago, Chicago, IL 60637, USA.

Our purpose was to determine the factors that correlate with healthy older adults' intention to get tested for mild cognitive impairment (MCI) under 3 different hypothetical conditions: (1) if they noticed they were having memory problems; (2) if a family member suggested that they are having memory problems; or (3) as part of a regular medical examination. Older adults were recruited from the waiting rooms of 2 geriatrics outpatient clinics for face-to-face interviews regarding their interest in being screened for MCI. A short description of MCI adapted from The Alzheimer's Association's "Fact Sheet" was presented before asking about MCI testing. Multivariable ordinal regression was used to account for heavily skewed outcome data showing very high levels of interest in screening for MCI. The strongest, most consistent correlate across all of the intention measures was the desire to know as early as possible if one has Alzheimer disease. Another robust correlate was having had normal memory testing in the past. Older adults appear to have psychologically connected MCI to Alzheimer disease, but how well they understand this connection is not known and requires further study.
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July 2008