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Elizabeth A Stewart

Publications and source records attributed to Elizabeth A Stewart.

At least 19 recordsLinked to original sources
PubMed2026

Pediatric sarcomas: challenges and opportunities.

Pediatric sarcomas are a heterogeneous group of rare mesodermal malignancies. These cancers, which affect children from infancy through adolescence and young adulthood, are in general challenging to treat with currently available therapies. Biologically, many are characterized by quiet genomes, fusion oncoproteins, immune "cold" microenvironments, and vast epigenetic deregulation that contributes to diverse and complex mechanistic drivers. Multifaceted advancements in research strategies, including high-throughput screening, new model systems, surfaceome profiling, and study of oncogenic fusion condensates have led to new opportunities for understanding the biology of pediatric sarcomas. To continue to make progress for these difficult to treat cancers, it will be critical to continue to improve access to bioinformatic data, approach patient care using innovative clinical trial frameworks, and foster interdisciplinary partnerships among medicinal chemists, scientists, clinicians, advocates, and industry partners.

Humans↗
PubMed2006

New interventional techniques for adenomyosis.

This chapter demonstrates that new interventional techniques have been introduced over recent years in order to find an adequate non-invasive therapy for adenomyosis. There is no evidence-based medicine to guide us in the treatment of adenomyosis with minimally invasive therapy. In fact, most data regarding adenomyosis and these evolving therapies comes from the inadvertent treatment of adenomyosis in studies designed to treat uterine leiomyomas. Essentially, all data are from case reports or small case series. The problem is compounded by the fact that there is no agreed imaging definition of adenomyosis, and so therapies that do not excise the uterus have no 'gold standard' for comparison. Nonetheless, there are some reports suggesting that there may be efficacy in techniques such as medicated intrauterine devices, uterine artery embolization, and MRI-guided focused ultrasound surgery. Larger studies specifically treating adenomyosis are clearly required. As with every new approach, the widespread success of these techniques will depend on the general adoption of adequate diagnostic solutions and improvements in the technical parameters of these new regimens. Since the techniques presented in this chapter are new, they have not yet undergone the necessary thorough scientific scrutiny and discussion that is needed for their general acceptance. In the past, adenomyosis was mainly a 'post-factum' pathological diagnosis after extensive surgery. Based on the evidence presented in this chapter it seems that adenomyosis has become an entity that might be treatable by new, minimally invasive or non-invasive treatments.

Adult↗
PubMed2006

Does the phase of menstrual cycle affect MR-guided focused ultrasound surgery of uterine leiomyomas?

PURPOSE: To determine whether the phase of menstrual cycle at the time of MR-guided focused ultrasound surgery (MRgFUS) treatment for uterine leiomyomas affects treatment outcome. METHODS: We enrolled all patients participating in a prospective phase III clinical trial from our center who completed 6 months of clinical and imaging follow-up. Patients with irregular cycles and those on oral contraceptives were excluded. Data prospectively documenting the date of the last menstrual period (LMP) at the time of treatment, length and duration of cycle, and raw symptom severity score (SSS) from the Uterine Fibroid Symptom and Quality of Life questionnaire, at baseline and 6 months were collected. Proliferative phase patients were determined retrospectively as those who were treated within less than 14 days from LMP; secretory phase patients were classified as those who were treated greater than 14 days from LMP. RESULTS: A total of 58 patients were enrolled. There was no significant difference in the mean SSS at baseline and mean SSS at 6 months between patients treated in the proliferative versus secretory phase of the cycle. No significant difference in the SSS change from baseline to 6 months was seen between the two groups. CONCLUSIONS: Menstrual cycle phase does not influence MRgFUS treatment outcome. Symptomatic improvement occurs with treatment during either phase of the menstrual cycle. Thus, the scheduling of MRgFUS treatment need not be based upon the phase of the menstrual cycle.

Female↗
PubMed2006

Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids.

OBJECTIVE: To assess outcomes at 6 and 12 months after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine leiomyomas. DESIGN: Multicenter clinical trial. SETTING: Academic medical centers. PATIENT(S): Premenopausal women with symptomatic uterine leiomyomas and no plans for future pregnancy (n = 109 at 6 months and n = 82 at 12 months). INTERVENTION(S): A single treatment session of MRgFUS for uterine fibroids. MAIN OUTCOME MEASURE(S): Reduction in fibroid symptoms as measured by the symptom severity score (SSS) of the Uterine Fibroid Quality-of-Life Instrument (UFS-QOL), the only validated measure of leiomyoma symptomatology. A 10-point reduction in the SSS was selected as the targeted improvement. RESULT(S): Seventy-one percent of women undergoing MRgFUS reached the targeted symptom reduction at 6 months, and 51% reached this at 12 months. The magnitude of improvement in SSS was greater than predicted, with subjects having a mean decrease of 39% and 36% at 6 and 12 months, respectively. This paralleled the improvement seen using the short form-36 instrument. A modest volume reduction similar in magnitude to the treated volume was seen. The incidence of adverse events was low. CONCLUSION(S): MRgFUS treatment results in short-term symptom reduction for women with symptomatic uterine leiomyomas with an excellent safety profile.

Adult↗
PubMed2006

Uterine artery embolization versus myomectomy: a multicenter comparative study.

OBJECTIVE: To determine whether there is significant quality of life score improvement after uterine artery embolization (UAE) and to compare UAE and myomectomy outcomes. DESIGN: Prospective cohort controlled study. SETTING: Sixteen medical centers in the United States. PATIENT(S): One hundred forty-nine UAE patients and 60 myomectomy patients. Patients were assigned to myomectomy or UAE on the basis of a best treatment decision made by the patient and her physician. All patients were observed for 6 months. The UAE patients also had follow-up examinations at 1 year. INTERVENTION(S): Myomectomy or UAE. MAIN OUTCOME MEASURE(S): Quality of life score changes, menstrual bleeding score changes, uterine size differences, time off, and adverse events. RESULT(S): Both groups experienced statistically significant improvements in the uterine fibroid quality of life score, menstrual bleeding, uterine volume, and overall postoperative quality of life. The mean hospital stay was 1 day for the UAE patients, compared with 2.5 days for the myomectomy patients. The UAE and myomectomy patients returned to their normal activities in 15 days and 44 days, respectively, and returned to work in 10 days and 37 days, respectively. At least one adverse event occurred in 40.1% of the myomectomy patients, compared with 22.1% in the UAE group. CONCLUSION(S): The uterine fibroid quality of life score was significantly improved in both groups. No significant differences were observed in bleeding improvement, uterine volume reduction, uterine fibroid quality of life score improvement, and overall quality of life score improvement between groups. Patients receiving UAE required fewer days off work, fewer hospital days, and experienced fewer adverse events.

Adult↗
PubMed2006

The genetics of uterine leiomyomata: what clinicians need to know.

The genetics of many complex diseases, including hypertension, diabetes, and asthma, are receiving intense investigation and beginning to have therapeutic relevance. Family medical history can be a critical source of information for providing optimal patient care. For gynecologists, knowledge of cancer susceptibility genes such as BRCA1 and BRCA2 and the genetic syndrome hereditary nonpolyposis colorectal cancer (Lynch syndrome II) affects how patients are screened for ovarian and endometrial cancers. Similarly, identification of mutations in the fumarate hydratase (FH) gene that lead to a syndrome called hereditary leiomyomatosis and renal cell carcinoma (HLRCC) will impact screening and treatment of women with uterine leiomyomas. Hereditary leiomyomatosis and renal cell carcinoma syndrome is particularly relevant to clinicians and patients because of the resulting increased risk of malignant disease for both the affected woman and her family. The goals of this article are to summarize the evolving genetic information concerning uterine leiomyomas, including hereditary leiomyomatosis and renal cell carcinoma syndrome, and to discuss the clinical importance of these findings. The current role of family medical history and future implications of genes relevant to leiomyoma biology will be reviewed.

Adult↗
PubMed2006

DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets.

Platelets can engulf human immunodeficiency virus type 1 (HIV-1), and a significant amount of HIV-1 in the blood of infected individuals is associated with these cells. However, it is unclear how platelets capture HIV-1 and whether platelet-associated virus remains infectious. DC-SIGN and other lectins contribute to capture of HIV-1 by dendritic cells (DCs) and facilitate HIV-1 spread in DC/T-cell cocultures. Here, we show that platelets express both the C-type lectin-like receptor 2 (CLEC-2) and low levels of DC-SIGN. CLEC-2 bound to HIV-1, irrespective of the presence of the viral envelope protein, and facilitated HIV-1 capture by platelets. However, a substantial fraction of the HIV-1 binding activity of platelets was dependent on DC-SIGN. A combination of DC-SIGN and CLEC-2 inhibitors strongly reduced HIV-1 association with platelets, indicating that these lectins are required for efficient HIV-1 binding to platelets. Captured HIV-1 was maintained in an infectious state over several days, suggesting that HIV-1 can escape degradation by platelets and might use these cells to promote its spread. Our results identify CLEC-2 as a novel HIV-1 attachment factor and provide evidence that platelets capture and transfer infectious HIV-1 via DC-SIGN and CLEC-2, thereby possibly facilitating HIV-1 dissemination in infected patients.

Animals↗
PubMed2006

Uterine leiomyomas: MR imaging-based thermometry and thermal dosimetry during focused ultrasound thermal ablation.

PURPOSE: To retrospectively evaluate magnetic resonance (MR) imaging-based thermometry and thermal dosimetry during focused ultrasound treatments of uterine leiomyomas (ie, fibroids). MATERIALS AND METHODS: All patients gave written informed consent for the focused ultrasound treatments and the current HIPAA-compliant retrospective study, both of which were institutional review board approved. Thermometry performed during the treatments of 64 fibroids in 50 women (mean age, 46.6 years +/- 4.5 [standard deviation]) was used to create thermal dose maps. The areas that reached dose values of 240 and 18 equivalent minutes at 43 degrees C were compared with the nonperfused regions measured on contrast material-enhanced MR images by using the Bland-Altman method. Volume changes in treated fibroids after 6 months were compared with volume changes in nontreated fibroids and with MR-based thermal dose estimates. RESULTS: While the thermal dose estimates were shown to have a clear relationship with resulting nonperfused regions, the nonperfused areas were, on average, larger than the dose estimates (means of 1.9 +/- 0.7 and 1.2 +/- 0.4 times as large for areas that reached 240- and 18-minute threshold dose values, respectively). Good correlation was observed for smaller treatment volumes at the lower dose threshold (mean ratio, 1.0 +/- 0.3), but for larger treatment volumes, the nonperfused region extended to locations within the fibroid that clearly were not heated. Variations in peak temperature increase were as large as a factor of two, both between patients and within individual treatments. On average, the fibroid volume reduction at 6 months increased as the ablated volume estimated by using the thermal dose increased. CONCLUSION: Study results showed good correlation between thermal dose estimates and resulting nonperfused areas for smaller ablated volumes. For larger treatment volumes, nonperfused areas could extend within the fibroid to unheated areas.

Adult↗
PubMed2005

Uterine fibroids: the elephant in the room.

Uterine fibroids (leiomyomas) have historically been viewed as important chiefly as the major indication for hysterectomy. As new therapies are developed, the heterogeneity of this disease becomes therapeutically relevant. An awareness of the role of genetics, the extracellular matrix, and hormones in tumor etiology is key to understanding this disease.

Animals↗
PubMed2005

Age-specific incidence rates for self-reported uterine leiomyomata in the Black Women's Health Study.

OBJECTIVE: Uterine leiomyomata represent a major public health problem for black women in the United States, but limited data are available on age-incidence curves in this high-risk population. We estimated overall and age-specific incidence rates for self-reported uterine leiomyomata in a large cohort of African-American women in the United States. METHODS: Data were derived from the Black Women's Health Study, an ongoing prospective cohort study of 59,000 black women from across the United States who were aged 21-69 years at baseline (ie, 1995). From March 1997 through March 2001, we followed up 22,895 premenopausal women with no prior diagnosis of uterine leiomyoma. Poisson regression was used to estimate overall and age-specific incidence rates and 95% confidence intervals (CIs) for self-reported uterine leiomyoma. In a subset of 248 patients who were selected randomly from the total case group, the self-reported diagnosis was verified in 96% of cases who released their medical records. RESULTS: During 76,711 woman-years of follow-up, 2,637 incident cases of uterine leiomyomata reported as confirmed by pelvic examination (n = 358), ultrasonography (n = 2,006), or hysterectomy (n = 273) were observed. Incidence rates per 1,000 woman-years were 34.4 (95% CI 33.1-35.7) for all cases combined, 29.7 (95% CI 28.5-30.9) for cases confirmed by ultrasonography or hysterectomy, and 3.6 (95% CI 3.2-4.0) for cases confirmed by hysterectomy. The incidence rate peaked at ages 40-44 years for all cases combined (incidence rate 45.6, 95% CI 42.0-49.5) and for cases confirmed by ultrasonography or hysterectomy (incidence rate 39.8, 95% CI 36.5-43.4), and peaked at ages 45-49 years for cases confirmed by hysterectomy (incidence rate 8.3, 95% CI 6.4-10.7). CONCLUSION: Overall incidence rates for self-reported uterine leiomyomata were consistent with other U.S studies in black women and confirmed a high burden of disease in this population. Age-specific incidence rates showed a later peak incidence than that observed among U.S. black women in previous studies.

Adult↗
PubMed2005

Influence of body size and body fat distribution on risk of uterine leiomyomata in U.S. black women.

BACKGROUND: Uterine leiomyomata are a major source of morbidity in black women. We prospectively investigated the risk of self-reported uterine leiomyomata in relation to body mass index (BMI), weight change, height, waist and hip circumferences, and waist-to-hip ratio in a large cohort of U.S black women. METHODS: Data were derived from the Black Women's Health Study, a U.S. prospective cohort study of black women who complete biannual mailed health questionnaires. From 1997 through 2001, we followed 21,506 premenopausal women with intact uteri and no prior diagnosis of uterine leiomyomata. Cox regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: After 70,345 person-years of follow up, 2146 new cases of uterine leiomyomata confirmed by ultrasound (n = 1885) or hysterectomy (n = 261) were self-reported. Compared with the thinnest women (BMI <20.0 kg/m), the multivariate IRRs for women with BMIs of 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-32.4, and 32.5+ kg/m were 1.34 (95% CI = 1.02-1.75), 1.39 (1.07-1.81), 1.45 (1.12-1.89), 1.47 (1.11-1.93), 1.36 (1.02-1.80), and 1.21 (0.93-1.58), respectively. IRRs were larger among parous women. Weight gain since age 18 was positively associated with risk, but only among parous women. No other anthropometric measures were associated with risk. CONCLUSIONS: BMI and weight gain exhibited a complex relation with risk of uterine leiomyomata in the Black Women's Health Study. The BMI association was inverse J-shaped and findings were stronger in parous women. Weight gain was positively associated with risk among parous women only.

Adipose Tissue↗
PubMed2004

Risk of uterine leiomyomata in relation to tobacco, alcohol and caffeine consumption in the Black Women's Health Study.

BACKGROUND: Tobacco, alcohol and caffeine consumption may influence risk of uterine leiomyomata via changes in ovarian function or hormone metabolism. METHODS: We prospectively assessed the relation of these exposures to risk of self-reported uterine leiomyomata in the Black Women's Health Study. From 1997 to 2001, we followed 21,885 premenopausal women with intact uteri and no prior myoma diagnosis. Cox regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: During 73,426 person-years of follow-up, 2177 incident cases of uterine leiomyomata confirmed by ultrasound (n = 1920) or hysterectomy (n = 257) were reported. Cigarette smoking was not associated with risk of uterine leiomyomata. Risk was positively associated with years of alcohol consumption and current consumption of alcohol, particularly beer. Relative to non-drinkers, multivariate IRRs for beer consumption of < 1, 1-6 and 7+ drinks/week were 1.11 (95% CI 0.98-1.27), 1.18 (95% CI 1.00-1.40) and 1.57 (95% CI 1.17-2.11), respectively. Heavy coffee and caffeine consumption were not associated with risk overall, but IRRs were increased among women aged < 35 years. CONCLUSIONS: In US black women, risk of uterine leiomyomata was positively associated with current consumption of alcohol, particularly beer. Cigarette smoking and caffeine consumption were unrelated to risk overall.

Adult↗
PubMed2004

Reproductive factors, hormonal contraception, and risk of uterine leiomyomata in African-American women: a prospective study.

The authors assessed the risk of uterine leiomyomata in relation to reproductive factors and hormonal contraception in a prospective cohort study of US Black women. From March 1997 through March 2001, the authors followed 22,895 premenopausal women with intact uteri and no prior self-reported diagnosis of uterine leiomyomata. The authors used age- and time-stratified Cox regression models to estimate incidence rate ratios for self-reported uterine leiomyomata, confirmed by ultrasound or hysterectomy, in association with selected reproductive and hormonal factors. During 76,711 person-years of follow-up, 2,279 new cases of ultrasound- or hysterectomy-confirmed uterine leiomyomata were self-reported. After adjustment for age, body mass index, smoking, alcohol intake, and other reproductive covariates, the risk of ultrasound- or hysterectomy-confirmed leiomyomata was inversely associated with age at menarche, parity, and age at first birth and positively associated with years since last birth. Overweight or obesity appeared to attenuate the inverse association between parity and uterine leiomyomata. Current use of progestin-only injectables was inversely associated with risk. No consistent patterns were observed for other forms of hormonal contraception. Reproductive history is an important determinant of leiomyomata risk in premenopausal US Black women. Progestin-only injectables may reduce risk.

Adult↗
PubMed2004

Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: genetic linkage analysis and FISH studies.

Recently, germline mutations of the fumarate hydratase (FH) gene, in 1q42.1, have been found to be involved in syndromes associated with uterine leiomyomas (ULs). Compelling evidence also supports a genetic liability to develop nonsyndromic UL, although susceptibility genes have not been reported to date. Loss of heterozygosity (LOH) studies have found no or rare evidence of LOH of FH in nonsyndromic UL. However, the karyotypes of these tumors were not reported, and cytogenetic aberrations of 1q42-44 have been observed infrequently in UL. To determine whether FH mutations also may predispose women to developing nonsyndromic UL, we performed a genetic linkage study with DNA from 123 families containing at least one affected sister pair. In addition, to assess the frequency of FH loss specifically in UL with 1q rearrangements, we performed a fluorescence in situ hybridization (FISH) analysis of UL with 1q rearrangements. Analysis of the genotyping data revealed evidence suggestive of linkage to the FH region among study participants who were less than 40 years of age at diagnosis (Zlr 1.7 at D1S547, P = 0.04). FISH results showed that one copy of FH was absent in 9 of 11 ULs. These data indicate that loss of FH might be a significant event in the pathogenesis of a subset of nonsyndromic ULs.

Adult↗
PubMed2003

Focused ultrasound treatment of uterine fibroid tumors: safety and feasibility of a noninvasive thermoablative technique.

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of focused ultrasound surgery with magnetic resonance imaging guidance for the noninvasive treatment of uterine leiomyomas. STUDY DESIGN: Fifty-five women with clinically significant uterine leiomyomas were treated. Pain and complications were assessed prospectively, and posttreatment magnetic resonance imaging was used to measure the treatment effects. Patients in three of the five centers underwent planned hysterectomy after treatment, which provided pathologic correlation of treatment. RESULTS: Seventy-six percent of the enrolled patients completed the full treatment session. All treatments were conducted in an outpatient setting with minimal discomfort for subjects and no major complications. Pathologic examination of the uterus confirmed that magnetic resonance imaging guidance provides the safe and accurate delivery of effective levels of thermal energy with a 3-fold increase in volume of histologically documented necrosis, compared with treatment volume (6.6 +/- 0.8 vs 18.4 +/- 3.9 mL, P <.005). CONCLUSION: Magnetic resonance imaging-guided focused ultrasound surgery appears to be a well-tolerated treatment for uterine leiomyomas.

Adult↗
PubMed2003

MR imaging-guided focused ultrasound surgery of uterine leiomyomas: a feasibility study.

The feasibility and safety of magnetic resonance (MR) imaging-guided focused ultrasound surgery for uterine leiomyomas is reported. Sequential sonications were delivered to nine targets. Temperature-sensitive phase-difference MR imaging monitored the location of the focus and measured tissue temperature elevations, ensuring therapeutic dose. MR images and hysterectomy specimens were evaluated. Six leiomyomas received full therapeutic doses, and 98.5% of the sonications were visualized. MR thermometry was successful in all sonications and cases. Focal necrotic lesions were seen in all cases at MR, and five were pathologically confirmed. MR imaging-guided focused ultrasound causes thermocoagulation and necrosis in uterine leiomyomas and is feasible and safe, without serious consequences.

Adult↗
PubMed2003

Neuropathic uterine pain after hysterectomy. A case report.

BACKGROUND: Neuropathic pain arises when there is damage to or dysfunction of the nervous system. Diabetic neuropathy, postherpetic neuralgia and phantom limb pain are common types of neuropathic pain. It is not commonly recognized in gynecologic practice. CASE: A patient underwent a hysterectomy for a tuboovarian abscess and underlying endometriosis. Despite maximal dosing with conventional pain medications, she continued to have significant pain that had not been present following prior surgeries. Use of low-dose amitriptyline successfully treated the pain, with no sequelae. CONCLUSION: Persistent pain following gynecologic surgery that does not respond to conventional therapy may have a neuropathic origin. Attention to appropriate history and physical examination may lead to an increase in the diagnosis of neuropathic pain in gynecology patients. This may have implications for persistent pain in other gynecologic diseases.

Abscess↗