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- Uterine Angioleiomyoma: A Rare Variant of Uterine Leiomyoma. [JOURNAL ARTICLE]
- Arch Pathol Lab Med 2014 Aug; 138(8):1115-1118.
Uterine angioleiomyoma is an extremely rare and unique variant of leiomyoma. It usually occurs in middle-aged women, who commonly present with menorrhagia, abdominal pain, or abdominal mass. The lesions are either single or multiple and manifest as submucosal, intramural, or subserosal whorled nodules. Microscopy of the individual nodule shows interlacing fascicles of spindle cells swirling around thick-walled blood vessels. Angioleiomyoma usually lacks mitotic figures, pleomorphism, or necrosis, although cases with marked nuclear atypia and multinucleated giant cells have been reported. The tumor cells are immunoreactive for smooth muscle actin, desmin, h-caldesmon, and progesterone receptor, with a low Ki-67 labeling index. Because these lesions are vascular, they may undergo spontaneous rupture and pose a life-threatening emergency, especially in pregnancy. There are no specific imaging findings; therefore, a preoperative diagnosis is extremely difficult. It is important to recognize this entity and differentiate it from a malignancy, particularly when angioleiomyoma shows significant cytologic atypia or raised cancer antigen 125 levels by thorough sampling. When required, a proper immunohistochemical panel should be used to arrive at a correct diagnosis. In this review, we discuss the current knowledge on uterine angioleiomyoma and its clinical relevance.
- Epigenetic Regulation of Uterine Biology by Transcription Factor KLF11 via Post-translational Histone Deacetylation of Cytochrome p450 Metabolic Enzymes. [JOURNAL ARTICLE]
- Endocrinology 2014 Jul 30.:en20141139.
Endocrine regulation of uterine biology is critical for embryo receptivity and human reproduction. Uterine endometrium depends on extrinsic sex steroid input and hence likely has mechanisms that enable adaptation to hormonal variation. Emerging evidence suggests that sex steroid bioavailability in the endometrium is determined by adjusting their metabolic rate and fate via regulation of cytochrome (CYP) p450 enzymes. The CYP enzymes are targeted by ubiquitously expressed Sp/KLF transcription factors. Specifically, KLF11 is highly expressed in reproductive tissues, regulates an array of endocrine/metabolic pathways via epigenetic histone-based mechanisms and when aberrantly expressed, is associated with diabetes and reproductive tract diseases such as leiomyoma and endometriosis. Using KLF11 as a model to investigate epigenetic regulation of endometrial first pass metabolism, we evaluated the expression of a comprehensive array of metabolic enzymes in Ishikawa cells. KLF11 repressed most endometrial CYP enzymes. To characterize KLF11-recruited epigenetic regulatory mechanisms we focused on the estrogen metabolizing enzyme CYP3A4. KLF11 expression declined in secretory phase endometrial epithelium associated with increased CYP3A4 expression. Additionally, KLF11 bound to CYP3A4 promoter GC elements and thereby repressed promoter, message, protein as well as enzymatic function. This repression was epigenetically mediated as KLF11 co-localized with and recruited the co-receptor SIN3A/HDAC (Histone deacetylase) resulting in selective deacetylation of the CYP3A4 promoter. Repression was reversed by a mutation in KLF11 that abrogated cofactor recruitment and binding. This repression was also pharmacologically reversible with an HDAC inhibitor. Pharmacological alteration of endometrial metabolism could have long-term translational implications on human reproduction and uterine disease.
- Clinical experience with treatment of angioleiomyoma. [Journal Article]
- Arch Plast Surg 2014 Jul; 41(4):374-8.
Angioleiomyoma, a vascular leiomyoma, is a rare, benign smooth-muscle tumor that originates in the tunica media of vessels. It occurs anywhere in the body, most frequently in the lower extremities.We reviewed the medical records of 16 patients who were treated for angioleiomyoma between 2000 and 2012. The clinical features of angioleiomyoma and the correlation between symptoms and pathological subtypes were investigated.There were 9 males and 6 females. Ages of the patients ranged from 21 to 61. Pain was the primary symptom in 44% of the patients. Tumors were smaller than 2.0 cm in all dimensions and were located in the face in 4 patients, whereas 5 lesions occurred in the upper extremities and the remaining 7 in the lower extremities. Three histologic subtypes were identified: solid, venous, and cavernous. The subtypes did not correlate with the clinical symptoms.Angioleiomyoma appears to be a rare tumor that occurs in the face and the extremities. The tumor usually occurs in middle age. A differential diagnosis of this tumor is difficult, but the tumor should be considered in the diagnosis of painful subcutaneous masses. Ultrasonography and magnetic resonance imaging can be helpful in the diagnosis of angioleiomyoma. These tumors can be successfully treated with simple excision, with a low recurrence rate.
- Cellular senescence in usual type uterine leiomyoma. [JOURNAL ARTICLE]
- Fertil Steril 2010 Nov; 94(6):e80.
- Power Morcellators: A Review of Current Practice and Assessment of Risk. [JOURNAL ARTICLE]
- Am J Obstet Gynecol 2014 Jul 26.
Power morcellation has come under scrutiny due to a highly publicized case of disseminated leiomyosarcoma following a laparoscopic hysterectomy. A recent FDA safety communication discouraging use of power morcellators on presumed uterine leiomyoma further highlights the need for re-examination of uterine tissue extraction. This clinical opinion aims to summarize current approaches to uterine/fibroid tissue extraction including the associated immediate and long-term potential risks of open power morcellation. The known data about risk of uterine sarcoma is reviewed followed by a discussion of acceptable risk and informed consent in the context of shared-decision making.
- Progesterone and Estradiol Synergistically Promote the Lung Metastasis of Tuberin-Deficient Cells in a Preclinical Model of Lymphangioleiomyomatosis. [JOURNAL ARTICLE]
- Horm Cancer 2014 Jul 29.
Lymphangioleiomyomatosis (LAM) is a female-predominant lung disease that can lead to respiratory failure. LAM cells typically have inactivating tuberous sclerosis 2 (TSC2) mutations, leading to mTORC1 hyperactivation. The gender specificity of LAM suggests that female hormones contribute to disease progression. Clinical findings indicate that estradiol exacerbates LAM behaviors and symptoms. Although hormonal therapy with progesterone has been employed, the benefit in LAM improvement has not been achieved. We have previously found that estradiol promotes the survival and lung metastasis of cells lacking tuberin in a preclinical model of LAM. In this study, we hypothesize that progesterone alone or in combination with estradiol promotes metastatic behaviors of TSC2-deficient cells. In cell culture models of TSC2-deficient LAM patient-derived and rat uterine leiomyoma-derived cells, we found that progesterone treatment or progesterone plus estradiol resulted in increased phosphorylation of Protein Kinase B (Akt) and Extracellular signal-regulated kinases1/2 (ERK1/2), induced the proliferation, and enhanced the migration and invasiveness. In addition, treatment of progesterone plus estradiol synergistically decreased the levels of reactive oxygen species and enhanced cell survival under oxidative stress. In a murine model of LAM, treatment of progesterone plus estradiol promoted the growth of xenograft tumors; however, progesterone treatment did not affect the development of xenograft tumors of Tsc2-deficient cells. Importantly, treatment of progesterone plus estradiol resulted in alteration of lung morphology and significantly increased the number of lung micrometastases of Tsc2-deficient cells compared with estradiol treatment alone. Collectively, these data indicate that progesterone increases the metastatic potential of Tsc2-deficient LAM patient-derived cells in vitro and lung metastasis in vivo. Thus, targeting progesterone-mediated signaling events may have therapeutic benefit for LAM and possibly other hormonally dependent cancers.
- Effect of local endometrial injury on pregnancy outcomes in ovum donation cycles. [JOURNAL ARTICLE]
- Fertil Steril 2014 Jul 23.
To evaluate the effect of local endometrial injury (LEI) on clinical outcomes in ovum donation recipients.Retrospective cohort analysis of ovum donation cycles conducted from 2005 to 2012.Two private IVF centers.Total 737 ovum donation cycles.LEI by endometrial "scratch" with the use of a Pipelle catheter.Clinical pregnancy and live birth rates.No statistically significant differences were found in clinical pregnancy rates and live birth rates in cycles subjected to LEI compared with those without. Combination of LEI with fibroid uterus resulted with significantly higher clinical pregnancy rates compared with LEI in normal uterine anatomy.This is the first study done in ovum recipients who underwent LEI by a "scratch" procedure after failed implantation. Unlike most previous reports, which found improved pregnancy rates with the use of "scratch effect" or "minor endometrial injury" after repeated implantation failures in standard IVF with own eggs, we did not find any changes in implantation rates in a population of egg recipients following this procedure. In view of a possible positive effect of LEI in cycles with a previous four or more failures, prospective randomized controlled studies are warranted to better define the target population who may benefit from this intervention.
- Multi-Scale and Shape Constrained Localized Region-Based Active Contour Segmentation of Uterine Fibroid Ultrasound Images in HIFU Therapy. [Journal Article]
- PLoS One 2014; 9(7):e103334.
To overcome the severe intensity inhomogeneity and blurry boundaries in HIFU (High Intensity Focused Ultrasound) ultrasound images, an accurate and efficient multi-scale and shape constrained localized region-based active contour model (MSLCV), was developed to accurately and efficiently segment the target region in HIFU ultrasound images of uterine fibroids.We incorporated a new shape constraint into the localized region-based active contour, which constrained the active contour to obtain the desired, accurate segmentation, avoiding boundary leakage and excessive contraction. Localized region-based active contour modeling is suitable for ultrasound images, but it still cannot acquire satisfactory segmentation for HIFU ultrasound images of uterine fibroids. We improved the localized region-based active contour model by incorporating a shape constraint into region-based level set framework to increase segmentation accuracy. Some improvement measures were proposed to overcome the sensitivity of initialization, and a multi-scale segmentation method was proposed to improve segmentation efficiency. We also designed an adaptive localizing radius size selection function to acquire better segmentation results.Experimental results demonstrated that the MSLCV model was significantly more accurate and efficient than conventional methods. The MSLCV model has been quantitatively validated via experiments, obtaining an average of 0.94 for the DSC (Dice similarity coefficient) and 25.16 for the MSSD (mean sum of square distance). Moreover, by using the multi-scale segmentation method, the MSLCV model's average segmentation time was decreased to approximately 1/8 that of the localized region-based active contour model (the LCV model).An accurate and efficient multi-scale and shape constrained localized region-based active contour model was designed for the semi-automatic segmentation of uterine fibroid ultrasound (UFUS) images in HIFU therapy. Compared with other methods, it provided more accurate and more efficient segmentation results that are very close to those obtained from manual segmentation by a specialist.
- Acute pulmonary embolism caused by enlarged uterine leiomyoma: A rare presentation. [Journal Article]
- Am J Case Rep 2014.:300-3.
Female, 42 FINAL DIAGNOSIS: Acute pulmonary embolism Symptoms: Chest pain • dyspneaStreptokinase • Warfarin Clinical Procedure: - Specialty: Cardiology and Neoplasm.Management of emergency care.Deep venous thrombosis (DVT) and subsequent pulmonary embolism (PE) caused by pelvic vein compression are rare and life-threatening complications of leiomyoma of the uterus.We report a 42-year-old virgin woman with a history of leiomyoma who presented to the emergency department with complaints of dyspnea and pleuritic chest pain with transient spotting. On physical examination, she had a non-tender abdomen with a 20-week size uterus. Imaging investigations revealed an acute DVT in her left leg and a huge uterine-derived mass compressing the common iliac veins. Transesophageal echocardiography (TEE) demonstrated an echogenic mass in her right pulmonary artery consistent with thrombosis. The patient was completely cured using thrombolytic therapy and myomectomy, and was well at 1 year after thrombolysis.PE caused by pelvic vein compression is a rare complication of leiomyoma, which should be considered. Thrombolytic therapy associated with myomectomy can be implemented for treating such cases, and TEE can be used for diagnosing suspected high-risk PE.
- Performance of multidetector CT in the evaluation of the endometrium: Measurement of endometrial thickness and detection of disease. [JOURNAL ARTICLE]
- Clin Radiol 2014 Jul 21.
To evaluate the performance of multidetector computed tomography (MDCT) in the measurement of endometrial thickness and assessment for endometrial disease.Seventy-nine MDCT examinations, including sagittal reformats from isotropic data, were retrospectively evaluated for the presence of endometrial abnormality, endometrial thickness, and recommendation for transvaginal ultrasound (TVUS) after CT. The endometrial thickness was measured on sagittal images using two different methods, between the inner-to-inner hypoattenuating stripe, and when visible, between the outer-to-outer hyperattenuating stripe. TVUS performed within 48 h of CT in premenopausal and 1 month in postmenopausal patients served as reference standard. Interobserver agreement for endometrial thickness and abnormalities was assessed using concordance correlation (CC) and kappa statistics.Interobserver agreement for endometrial thickness on sagittal CT images was excellent (CC 0.98), and highly accurate using the inner-to-inner measurement. For determination of abnormal thickening, the positive predictive value and negative predictive value were 67-100% and 99.5-100%. For detection of any endometrial abnormality, the positive predictive value and negative predictive value were 79-90% and 84-95%, respectively. False-negative missed abnormalities included small volume hydrometra, a polyp, and endometrial distortion by a fibroid.At MDCT, sagittal reformatted images provide reliable endometrial measurement using the inner-to-inner hypoattenuating stripe and are accurately categorized as normal or abnormal thickness using the same numerical criteria as at sonography.