Uterine Fibroids Stewart, Elizabeth A
The New England journal of medicine,
04/2015, Letnik:
372, Številka:
17
Journal Article
Recenzirano
Fibroids, which are common in women of reproductive age, may cause heavy menstrual bleeding and symptoms related to leiomyoma bulk. Hysterectomy is an effective treatment, but many uterine-sparing ...options are available and should be discussed with patients.
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.
Stage
A 47-year-old black woman has heavy menstrual bleeding and iron-deficiency anemia. She reports nocturia and urinary frequency. A colonoscopy is negative. Ultrasonography shows a modestly enlarged uterus with three uterine fibroids. She is not planning to become pregnant. How should this case be evaluated and managed?
The Clinical Problem
Uterine fibroids (leiomyomas or myomas) are extremely common benign neoplasms of the uterus.
1
The lifetime prevalence of fibroids exceeds 80% among black women and approaches 70% among white women.
2
In a study using ultrasonographic screening, 51% of premenopausal women received a new diagnosis of fibroids.
2
Fibroids can cause heavy or . . .
Hysterectomy remains the one-size-fits-all treatment for uterine fibroids.
1
Despite the fact that more than 8000 women have participated in randomized clinical trials that compared uterine-artery ...embolization with surgery, only a few hundred of these women underwent myomectomy, the uterine-sparing alternative to hysterectomy.
2,3
Data are needed to compare outcomes among uterine-sparing options for the treatment of fibroids, and the findings of the FEMME trial (A Randomized Trial of Treating Fibroids with Either Embolisation or Myomectomy to Measure the Effect on Quality of Life Among Women Wishing to Avoid Hysterectomy), reported in this issue of the
Journal
,
4
further this effort. Hysterectomy has . . .
Investigation of the mechanisms responsible for aggressive neuroblastoma and its poor prognosis is critical to identify novel therapeutic targets and improve survival. Enhancer of Zeste Homolog 2 ...(EZH2) is known to play a key role in supporting the malignant phenotype in several cancer types and knockdown of EZH2 has been shown to decrease tumorigenesis in neuroblastoma cells. We hypothesized that the EZH2 inhibitor, GSK343, would affect cell proliferation and viability in human neuroblastoma. We utilized four long-term passage neuroblastoma cell lines and two patient-derived xenolines (PDX) to investigate the effects of the EZH2 inhibitor, GSK343, on viability, motility, stemness and in vivo tumor growth. Immunoblotting confirmed target knockdown. Treatment with GSK343 led to significantly decreased neuroblastoma cell viability, migration and invasion, and stemness. GSK343 treatment of mice bearing SK-N-BE(2) neuroblastoma tumors resulted in a significant decrease in tumor growth compared to vehicle-treated animals. GSK343 decreased viability, and motility in long-term passage neuroblastoma cell lines and decreased stemness in neuroblastoma PDX cells. These data demonstrate that further investigation into the mechanisms responsible for the anti-tumor effects seen with EZH2 inhibitors in neuroblastoma cells is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To report all pregnancies to date after magnetic resonance–guided focused ultrasound surgery (MRgFUS) for the conservative treatment of clinically significant uterine fibroids. Design ...Prospective registry of all known pregnancies occurring after MRgFUS maintained by the device manufacturer and reported to the Food and Drug Administration. Setting World experience of pregnancies after treatment with reports from 13 sites in seven countries. Patient(s) Fifty-one reproductive-age women with uterine leiomyomas. Intervention(s) Women underwent MRgFUS treatment for symptomatic uterine leiomyomas before this report. Main Outcome Measure(s) Pregnancy outcomes and complications. Result(s) Fifty-four pregnancies in 51 women have occurred after MRgFUS treatment of uterine leiomyomas. The mean time to conception was 8 months after treatment. Live births occurred in 41% of pregnancies, with a 28% spontaneous abortion rate, an 11% rate of elective pregnancy termination, and 11 (20%) ongoing pregnancies beyond 20 gestational weeks. The mean birth weight was 3.3 kg, and the vaginal delivery rate was 64%. Conclusion(s) Preliminary pregnancy experience after MRgFUS is encouraging, with a high rate of delivered and ongoing pregnancies.
Uterine Fibroids: The Elephant in the Room Walker, Cheryl Lyn; Stewart, Elizabeth A
Science (American Association for the Advancement of Science),
06/2005, Letnik:
308, Številka:
5728
Journal Article
Recenzirano
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.
Uterine fibroids (leiomyomas) are present in >75% of women and can cause serious morbidity. They are by far the leading cause of hysterectomy. Fibroids are a complex mixture of cells that include ...fibroblasts and smooth muscle cells. Rich in extracellular matrix, they typically arise through somatic mutations, most commonly
. Their lack of growth inhibition and their ability to have facets of malignancy yet be histologically and biologically benign provide opportunities to explore basic processes. To date, the mechanisms responsible for growth and development of leiomyomas are an enigma. This review provides an overview of current understanding and future directions for clinical and basic research of fibroids.
Objective We sought to characterize the impact of uterine leiomyomas (fibroids) in a racially diverse sample of women in the United States. Study Design A total of 968 women (573 white, 268 African ...American, 127 other races) aged 29-59 years with self-reported symptomatic uterine leiomyomas participated in a national survey. We assessed diagnosis, information seeking, attitudes about fertility, impact on work, and treatment preferences. Frequencies and percentages were summarized. The χ2 test was used to compare age groups. Results Women waited an average of 3.6 years before seeking treatment for leiomyomas, and 41% saw ≥2 health care providers for diagnosis. Almost a third of employed respondents (28%) reported missing work due to leiomyoma symptoms, and 24% believed that their symptoms prevented them from reaching their career potential. Women expressed desire for treatments that do not involve invasive surgery (79%), preserve the uterus (51%), and preserve fertility (43% of women aged <40 years). Conclusion Uterine leiomyomas cause significant morbidity. When considering treatment, women are most concerned about surgical options, especially women aged <40 years who want to preserve fertility.
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy in women under 40 years of age. We sequenced the exomes of six individuals from ...three families with SCCOHT. After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we tested DNA from a fourth affected family, which also carried a segregating SMARCA4 germline mutation. All the familial tumors sequenced harbored either a somatic mutation or loss of the wild-type allele. Immunohistochemical analysis of these cases and additional familial and non-familial cases showed loss of SMARCA4 (BRG1) protein in 38 of 40 tumors overall. Sequencing of cases with available DNA identified at least one germline or somatic deleterious SMARCA4 mutation in 30 of 32 cases. Additionally, the SCCOHT cell line BIN-67 had biallelic deleterious mutations in SMARCA4. Our findings identify alterations in SMARCA4 as the major cause of SCCOHT, which could lead to improvements in genetic counseling and new treatment approaches.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
