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1.  Differentiation of myomas by means of biomagnetic and doppler findings 
To elucidate the hemodynamics of the uterine artery myomas by use of Doppler ultrasound and biomagnetic measurements.
Twenty-four women were included in the study. Sixteen of them were characterised with large myomas whereas 8 of them with small ones. Biomagnetic signals of uterine arteries myomas were recorded and analyzed with Fourier analysis. The biomagnetic signals were distributed according to spectral amplitudes as high (140–300 ft/√Hz), low (50–110 ft/√Hz) and borderline (111–139 ft/√Hz). Uterine artery waveform measurements were evaluated by use of Pulsatility Index (PI) (normal value PI < 1.45).
There was a statistically significant difference between large and small myomas concerning the waveform amplitudes (P < 0.0005) and the PI index (P < 0.0005). Specifically, we noticed high biomagnetic amplitudes in most large myomas (93.75 %) and low biomagnetic amplitudes in most small ones (87.5 %).
It is suggested that the biomagnetic recordings of uterine artery myomas could be a valuable modality in the estimation of the circulation of blood cells justifying the findings of Doppler velocimetry examination.
PMCID: PMC1450278  PMID: 16584560
2.  CA 125 and other tumor markers in uterine leiomyomas and their association with lesion characteristics 
The aim of this study was to investigate the factors associated with serum levels of several tumor markers in a group of patients operated for uterine myoma. One hundred thirty-seven female patients operated for uterine myoma were included. Serum samples were examined for CA 125, CA 19-9, CA 15-3, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels as part of routine workup. Pathological and morphological characteristics of the patients were retrieved from medical records. The mean age was 46.7 ± 8.8 years (range, 22-85 y). Abnormally high levels of CA 125, CA 19-9, CA 15-3, CEA, and AFP were found in 19.7%, 6.6%, 5.1%, 3.7%, and 1.5% of the patients, respectively. Patients with additional adenomyosis and patients with at least one large myoma (≥ 5 cm diameter) had significantly higher levels of CA 125. Multivariate analysis identified coexistence of adenomyosis (OR 7.7 [95% CI, 2.6-23.0], p < 0.001) and presence of at least one large myoma (OR 5.6 [1.4-22.8], p = 0.016) as independent predictors of abnormally high CA 125 levels. CA 125 levels are affected by the tumor size and coexistence of adenomyosis in uterine leiomyomas. Indirect mechanisms caused by large myoma size such as peritoneal irritation may be responsible for CA 125 elevations.
PMCID: PMC4057864  PMID: 24955185
Uterine leiomyoma; uterine fibroma; tumor marker; CA 125; CA 19-9; CA 15-3; carcinoembryonic antigen (CEA); alpha fetoprotein (AFP)
3.  Low dose mifepristone in medical management of uterine leiomyoma - An experience from a tertiary care hospital from north India 
The Indian Journal of Medical Research  2013;137(6):1154-1162.
Background & objectives:
Uterine myoma is a common indication for hysterectomy in India. An effective medical treatment option may reduce hysterectomy associated morbidity. This study was undertaken to evaluate efficacy and safety of low dose mifepristone in medical management of myoma and to compare two doses - 10 vs. 25 mg/day.
In this randomized clinical trial, women with symptomatic myoma or myoma>5cm were included. Uterine size >20 wk, fibroids >15 cm were excluded. Pictorial blood loss assessment chart (PBAC) score was used to assess menstrual-blood-loss and visual analog scale (VAS) for other symptoms. Haemogram, liver function test, ultrasound with doppler and endometrial histology was performed. Patients were randomized and were given oral mifepristone as 25 mg/day in group 1 and 10 mg/day in group 2 for 3 months. Patients were followed at 1, 3 and 6 months.
Seventy patients in group 1 and 73 in group 2 completed treatment. Mean PBAC score reduced from 253 to 19.8 and from 289.2 to 10.4 at 1 and 3 months in groups 1 and 2, respectively. At 3 months, 67 of 70 (95.7%) patients of group 1 and 66 of 73 (90.4%) of group 2 developed amenorrhoea which reverted after median 34 (range 4-85) days. Mean myoma volume decreased by 35.7 per cent (from 176.8 to 113.7cm3) and 22.5 per cent (from 147.6 to 114.4 cm3) at 3 months in groups 1 and 2, respectively. Side effects seen were leg cramps in 7 of 70 (10%) and 5 of 73 (6.8%) and hot-flushes in 5 of 70 (7.1%) and 5 of 73 (6.8%) in groups 1 and 2, respectively. Repeat endometrial-histopathology did not reveal any complex hyperplasia or atypia in either group.
Interpretation & conclusions:
Mifepristone (10 and 25 mg) caused symptomatic relief with more than 90 per cent reduction in menstrual blood. Greater myoma size reduction occured with 25 mg dose. Amenorrhoea was developed in 90-95 per cent patients which was reversible. It can be a reasonable choice for management of uterine leiomyoma as it is administered orally, cost-effective and has mild side effects.
PMCID: PMC3734720  PMID: 23852296
Amenorrhoea; fibroid; leiomyoma; mifepristone; medical management; uterine
4.  Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity 
Fertility and sterility  2008;93(6):2027-2034.
Study objective
To evaluate the effect of uterine leiomyomas on the endometrium using molecular markers of endometrial receptivity: HOXA10, HOXA11, LIF, and BTEB1.
Case-control study
University medical center
Thirty reproductive-age women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy.
Proliferative phase endometrial sampling was performed at the time of surgery. In uteri with a submucosal myoma, directed endometrial biopsies were obtained over the myoma and over normal myometrium.
Main outcome measures
Endometrial HOXA10 expression was evaluated as a primary end point using quantitative real time RT-PCR and immunohistochemistry. HOXA11, BTEB1, and LIF were evaluated using real time RT-PCR.
Endometrial HOXA10 and HOXA11 mRNA expression were significantly decreased in uteri with submucosal myomas compared to controls and to uteri with intramural myomas. A similar trend was seen in BTEB1 mRNA expression, however no difference was found in LIF mRNA expression. Immunohistochemistry localized the decrease in endometrial HOXA10 protein expression to stroma. In the presence of a submucosal myoma, there were no regional differences in gene expression.
The molecular mechanism by which submucosal myomas adversely affect reproduction includes a global decrease in endometrial HOX gene expression, not simply a focal change over the myoma. This may explain the reproductive dysfunction observed with submucosal myomas.
PMCID: PMC3107853  PMID: 18555231
leiomyoma; fibroid; submucosal myoma; endometrium; endometrial receptivity; HOXA10
5.  The safety of cesarean myomectomy in women with large myomas 
Obstetrics & Gynecology Science  2014;57(5):367-372.
To evaluate the safety of cesarean myomectomy in large myomas sized >5 cm.
One hundred sixty-five pregnant women with myomas who delivered via cesarean section were identified. Ninety-six women had cesarean section without myomectomy, and 65 women underwent cesarean myomectomy. We compared the maternal characteristics, neonatal weight, myoma types, and operative outcomes between two groups. We further analyzed cesarean myomectomy group according to myoma size. The large myoma was defined as myoma >5 cm in size. The maternal characteristics, neonatal weight, and myoma types were compared between two groups. We also compared the operative outcomes such as preoperative and postoperative hemoglobin, operative time, and hospitalized days between two groups.
There were no significant differences in the maternal characteristics, myoma types, neonatal weight and operative outcomes between cesarean section without myomectomy and cesarean myomectomy. The subgroup analysis according to myoma size (>5 cm or not) in cesarean myomectomy group revealed that there were no significant differences in the mean hemoglobin change (1.2 vs. 1.3 mg/dL, P=0.6), operative time (90.5 vs. 93.1 minutes, P=0.46), and the length of hospital stay (4.7 vs. 5.2 days, P=0.15) between two groups. The comparison of maternal characteristics, neonatal weight, and myoma types between two groups also showed no statistical significance.
Cesarean myomectomy in patients with large myomas is a safe and effective procedure.
PMCID: PMC4175596  PMID: 25264526
Cesarean myomectomy; Large myoma; Safety
6.  Effects of Menopausal Hormone Therapy on Uterine Myoma in Menopausal Women 
Journal of Menopausal Medicine  2013;19(3):123-129.
The aim of the present study is to evaluate the long term effects of estrogen-progestogen therapy (EPT) on uterine myomas volume in postmenopausal women.
We performed a retrospective analysis on postmenopausal women with asymptomatic uterine myoma during the period between April, 2008 and September, 2012. Postmenopause was defined as amenorrhea for longer than a year or serum follicle stimulating hormone levels higher than 40 IU/L. The volume of the myoma was assessed by transvaginal ultrasonography for every 6 months after administration of EPT.
Thirty-eight women were included in the study, with 32 in the EPT group and 6 in the control group. Overall, uterine myoma volume (mean ± standard deviation, cm3) in the EPT group was 19.5 ± 24.6 at baseline, and those at 6 and 12 months were 24.7 ± 35.1 and 28.5 ± 56.4, respectively. Myoma volume did not change significantly with EPT, and these changes were not significantly different from the control group. Myoma volume changes were not significantly different in the subgroups according to the route of estrogen administrations and the method of progestogen administrations. Clinically significant volume increases during one year of EPT was noted in 28.1% (9/32), however, only one showed transient increases.
Our results suggest that treating postmenopausal woman with EPT on a long-term basis does not increase the volume of uterine myomas.
PMCID: PMC4217555  PMID: 25371877
Estrogens; Myoma; Postmenopause; Progesterone; Uterus
7.  Multiple Layer Closure of Myoma Bed in Laparoscopic Myomectomy 
To assess the feasibility and outcome of laparoscopic myomectomy and multiple layer closure of the myoma bed, for management of myomas, at a tertiary care hospital.
Materials and Methods:
From September 2005 to September 2010, 417 patients, with large and moderate size myomas, were managed by laparoscopic myomectomy. Indications were subfertility, menorrhagia, and abdominal mass. Preoperative evaluation included history, clinical examination, and sonographic mapping. The myomas were enucleated and retrieved laparoscopically. Myoma beds were sutured in multiple layers by endoscopic intracorporeal suturing.
Three hundred and fifteen patients presented with subfertility, 45 with menorrhagia, and 57 with abdominal mass. The average maximum diameter of a myoma was 9 cm. The mean duration of surgery was 120 minutes. The mean postoperative stay was 24 hours. No intraoperative complication occurred and the hospital course was uncomplicated. In one case, a minilap incision was performed for retrieval of the myoma with suturing of the bed. Two patients had minor delayed wound healing of the morcellator port site. The patients did not report any complaints during the follow-up, except one patient who developed omental hernia at the morcellator port site. There was no rupture of the scar and very low adhesion scores in the subsequent cesarean sections or second-look scopies.
With proper multilayer closure of the myoma bed, laparoscopic myomectomy was feasible for moderate and even large myomas and had excellent outcomes.
PMCID: PMC3304293  PMID: 22442535
Better reproductive outcome; laparoscopic myomectomy; large myomas; multilayer closure
8.  Effect of mifepristone (25 mg) in treatment of uterine myoma in perimenopausal woman 
Journal of Mid-Life Health  2013;4(1):22-26.
To evaluate the effect of Mifepristone (25 mg) on symptomatic myoma in perimenopausal women.
Study Design:
Open label clinical trial.
Materials and Methods:
Ninety three perimenopausal women of age 35-50 years having symptomatic myoma were selected from Gynecology OPD and given 25 mg Mifepristone once daily continuously for three months. Variables as; baseline uterine size, uterine volume, myoma size, volume, their number, position, characteristics, hemoglobin and blood parameters, were taken and followed monthly for six months. Bleeding and pain scores were checked on monthly visits. Changes in above parameters were tabulated during the first three months treatment phase and then next three post-treatment phase for analysis.
Statistical Analysis:
Was done by calculating mean, standard deviation, standard error and percentage distribution of variables.
Menorrhagia was the most common symptom which led patients to report to hospital. Mean uterine volume reduced to 63.69% of baseline, Mean dominant Myoma volume reduced to 53.62% and hemoglobin level raised to 137% after complete three months of treatment. Changes persisted in next three months post-treatment follow-up, while hysterectomy was required in 10 (12.2%) cases.
Three months treatment of 25 mg Mifepristone effectively controls bleeding, reduces the uterine and myoma volume and thus can avoid blood transfusion and hysterectomy in a lot of symptomatic myoma cases.
PMCID: PMC3702060  PMID: 23833529
Anti-progesterone; medical treatment; mifepristone; myoma
9.  Current and emerging treatments for uterine myoma – an update 
Uterine myomas, the most common benign, solid, pelvic tumors in women, occur in 20%–40% of women in their reproductive years and form the most common indication for hysterectomy. Various factors affect the choice of the best treatment modality for a given patient. Asymptomatic myomas may be managed by reassurance and careful follow up. Medical therapy should be tried as a first line of treatment for symptomatic myomas, while surgical treatment should be reserved only for appropriate indications. Hysterectomy has its place in myoma management in its definitiveness. However, myomectomy, rather than hysterectomy, should be performed when subsequent childbearing is a consideration. Preoperative gonadotropin-releasing hormone analog treatment before myomectomy decreases the size and vascularity of the myoma but may render the capsule more fibrous and difficult to resect. Uterine artery embolization is an effective standard alternative for women with large symptomatic myomas who are poor surgical risks or wish to avoid major surgery. Its effects on future fertility need further evaluation in larger studies. Serial follow-up without surgery for growth and/or development of symptoms is advisable for asymptomatic women, particularly those approaching menopause. The present article is incorporated with multiple clear clinical photographs and simplified elaboration of the available management options for these tumors of uterine smooth muscle to facilitate clear understanding.
PMCID: PMC3163653  PMID: 21892334
myomectomy; uterine artery embolization; pelvic tumor; hysterectomy; GnRH; leiomyoma
10.  Comparison of the Inhibitory Effect of Gonadotropin Releasing Hormone (GnRH) Agonist, Selective Estrogen Receptor Modulator (SERM), Antiprogesterone on Myoma Cell Proliferation In Vitro 
Uterine myomas are the most common gynecologic tumor in women of reproductive age. Treatment options of uterine myomas consist of surgical, medical and interventional therapy such as uterine artery embolization or myolysis. Given that it is the most common type of tumor in women of reproductive age, the treatment of uterine myomas must prioritize uterine conservation. There are several drugs for medical treatment of uterine myoma such as gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM) and antiprogesterone. The objective of this study was to compare the effect of GnRH agonist, SERM, and antiprogesterone in the treatment of uterine myomas in vitro. The effect of drugs was evaluated through the cell viability assay in cultured leiomyoma cells, western blot analysis of proliferating cell nuclear antigen (PCNA), and BCL-2 protein expression. As a result, mifepristone single-treated group represents the most significant reduction in myoma cell viability and proliferation. When pretreated with leuprolide acetate, raloxifene shows more significant reduction in myoma cell viability and proliferation than mifepristone. This study suggests one of the possible mechanisms how medications act on uterine myoma, especially at the molecular level.
PMCID: PMC3917117  PMID: 24516352
Leiomyoma; Drug therapy; Gonadotropin-releasing hormone agonist; Raloxifene; Mifepristone
11.  Uterine leiomyoma and its association with menstrual pattern and history of depo-medroxyprogesterone acetate injections 
Background and aim:
Despite the high prevalence of uterine leiomyoma, according to recent review studies there is uncertainty and a paucity of information regarding its predisposing or protective factors. The aim of this study was to assess the possible association between menstrual cycle pattern and occurrence of surgically treated myomas and also to check if depo-medroxyprogesterone acetate (DMPA) injection earlier in reproductive life can affect the later occurrence of myomas needing surgical treatment.
In a case–control study in Ardabil, 85 women with definite diagnosis of surgically treated uterine leiomyoma and 154 community controls were enrolled. Possible predictors of myoma including menstrual cycle and menstrual bleeding patterns were assessed. Data were analyzed using SPSS software (SPSS, IBM, Somers, NY). Odds ratios were used as the main statistic in assessing the strength of observed associations.
Mean age of the participants was 41.8 ± 8.5 years. Length of menstrual cycle was associated with myoma and a higher likelihood of myoma was observed among those having shorter menstrual cycles (P < 0.05). Number of menstrual bleeding days was also associated with surgically treated myoma and longer bleeding periods increased the likelihood of myoma (P < 0.05). Only one of the eight women who had a history of depo-medroxyprogesterone acetate injections had developed surgically treated uterine leiomyoma and the others belonged to the control group without a history of surgical treatment for uterine leiomyoma.
Menstrual cycle pattern is associated with developing leiomyomas requiring surgical treatment. DMPA, other than its role in myoma treatment, is also assumed to have a role in preventing myomas, but due to the small sample size in this study, larger scale prospective trials are needed in the future.
PMCID: PMC3150177  PMID: 21845062
myoma; uterine leiomyoma; DMPA; medroxyprogesterone; menstrual cycle; menstrual; depo-provera
12.  Leiomyomatosis peritonealis disseminata associated with endometriosis: A case report and review of the literature 
Oncology Letters  2014;9(2):717-720.
Leiomyomatosis peritonealis disseminata (LPD) is a specific type of leiomyomatosis with an unclear pathogenesis that is rarely diagnosed by clinical evaluation. To date, <200 cases have been reported. The majority of the patients have a medical history of laparoscopic myomectomy for uterine fibroids. The use of laparoscopic power morcellation may be a contributor to the development of LPD, therefore, the specific surgical approach used in laparoscopic myomectomy should be carefully considered, and protective measures should be taken to prevent myoma fragments spreading if laparoscopic power morcellation is used. The present study reviewed and analyzed the medical history, diagnostic process and treatment strategy of a case of LPD to improve our understanding of the disease. In this report, the case of a 34 year-old female who underwent laparoscopic myomectomy to remove a uterine fibroid is presented. During the surgery, a myoma was resected using morcellators. Three years after surgery, exploratory laparotomy was performed due to uterine fibroid recurrence. During surgery, myoma was identified at the uterine bladder peritoneal reflection, where several unequally sized leiomyoma tubercles were identified on the uterine surface. Subsequently, myomectomy was performed. Postoperative pathology diagnosed leiomyoma. Two years later, gynecological ultrasound revealed a mass in the abdomen. Exploratory laparotomy was subsequently performed. During surgery, compact myoma tubercle-like cysts were identified on the surface of the intestine and mesentery, and an endometriotic cyst was identified on the left ovary. As the myomas were too compact to remove completely, the majority of leiomyoma on the intestine and mesentery was resected. The endometriotic cyst on the left ovary was also resected. Considering the patient’s medical history, observations during surgery and pathological results, the final diagnosis was LPD. Following surgery, the patient was treated with the gonadotropin-releasing hormone agonist, triptorelin acetate (3.5 mg, once every four weeks), for three months and followed-up every six months. In October 2014, a gynecological sonography examination revealed no abnormalities and at the time of writing, the patient remains alive and well.
PMCID: PMC4301522  PMID: 25621042
leiomyomatosis; peritonealis disseminata; laparoscope; hysteromyomectomy; uterine fibroid; laparoscopic power morcellators
13.  Fertility outcomes following myomectomy in an urban hospital setting. 
OBJECTIVE: Infertility is rarely a consequence of myomas. However, a causal relationship may be suspected when other causes of infertility have been excluded. Uterine myomas have been reported in 27% of infertile women; 50% of women with unexplained infertility become pregnant after myomectomy. The objective of this study was to establish the impact of the surgical removal of myomas on fertility outcomes in women experiencing recurrent pregnancy loss or unexplained infertility. Fallopian tube, anovulatory disorders and male fertility factors had been appropriately excluded. DESIGN: This was a retrospective study in which we compiled data from the medical records of eight patients from 2003-2004 who underwent abdominal myomectomy for infertility or recurrent pregnancy loss. We calculated rates for subsequent spontaneous abortion, preterm delivery, cesarean delivery, malpresentation and postpartum hemorrhage. RESULTS: There were two patients who were nulliparous premyomectomy, and six had recurrent pregnancy losses. There was a cumulative success rate of 75% (six live births in eight patients) following myomectomy. One had two subsequent pregnancies. There were no spontaneous abortions. Three (37.5%) patients failed to conceive postmyomectomy, one of which was found to have bilateral tubal occlusion. Of the six pregnancies achieved, two (33%, 95% CI 2.06, 3.14) were preterm deliveries, six (100%, 95% CI 1.74, 3.50) were delivered by cesarean section and three (50%, 95% CI 3.50, 1.73) were malpresentations (two breech, one transverse lie). One patient (16%, 95% CI 2.06, 3.30) had abruptio placentae and two patients (33%, 95% CI 2.06, 3.14) experienced postpartum hemorrhage. CONCLUSION: This study suggests that there may be a beneficial effect of surgical removal of myomas on enhancing fertility and successful pregnancy outcome. However, the sample was too small to achieve statistical significance.
PMCID: PMC2594713  PMID: 16353656
14.  The Indications, Surgical Techniques, and Limitations of Laparoscopic Myomectomy 
To assess the indications and limits of laparoscopic myomectomies (LM).
We conducted a retrospective analysis of 89 consecutive cases of LM. Our LM procedures were as follows: Diluted vasopressin was injected into the myoma capsule, and a transverse incision was made by fine monopolar electrode. Traction was applied to the myoma with a myoma screw. The uterine wall was sutured with a curved needle. Fibrin glue spray was applied to prevent adhesion formation. Enucleated myomas were removed via trocar by using an electric morcellator.
We enucleated 195 nodules with diameters > 2 cm; the mean size of the dominant myomas was 5.3 cm. The mean number of myomas removed from each patient was 2. The uterine wall was sutured in all cases with a mean of 9 sutures. The mean blood loss was 102 mL, and the mean operating time was 111 minutes. No patients were converted to laparotomy. The average hospital stay was 2.4 days. When the myomas were larger than 10 cm, the blood loss and operating time were increased. However, the number of myomas did not correlate with blood loss.
LM appears to offer a number of advantages if the myoma is not larger than 10 cm.
PMCID: PMC3015481  PMID: 12856836
Laparoscopic myomectomy; Surgical technique; Indication; Limitation
15.  Laparoscopic Surgical Management and Clinical Characteristics of Ovarian Fibromas 
Ovarian fibromas may be misdiagnosed as uterine myoma or ovarian malignant tumor. Laparoscopic examination appears to be an effective and safe surgical approach for managing ovarian fibromas.
This study aims to analyze the clinical characteristics and diagnostic features of ovarian fibromas and to evaluate the efficacy and safety of laparoscopic surgery for ovarian fibromas.
We reviewed the records of 47 consecutive women who underwent laparoscopic or laparotomic surgeries and whose final histopathological diagnoses were ovarian fibroma, cellular fibroma, or fibrothecoma from January 1999 to August 2010.
During the study period, 49 tumors were removed from 47 women including 27 ovarian fibromas, 19 fibrothecomas, and 3 cellular fibromas. The preoperative diagnoses were ovarian fibroma in 25 women (53.2%) and uterine myoma in 16 women (34.0%). A high serum CA 125 level (>35U/mL) was observed in 15 women, and serum CA 125 level was significantly higher in women with ascites (P=<0.001). The tumors were removed surgically in all women, using the laparotomic approach in 16 women (34.0%) and the laparoscopic approach in 31 women (66.0%). The laparoscopic surgery had the advantages of shorter hospital stay and faster return of bowel activities compared to laparotomy.
Ovarian fibromas are often misdiagnosed as uterine myomas, and sometimes mistaken for a malignant tumor of the ovary preoperatively. Laparoscopic surgery can be an effective and safe surgical approach for managing ovarian fibromas.
PMCID: PMC3134689  PMID: 21902936
Cellular fibroma; Fibroma; Fibrothecoma; Laparoscopy; Ovary
16.  Laparoscopic Myomectomy for Very Large Myomas Using an Isobaric (Gasless) Technique 
Laparoscopic myomectomy using pneumoperitoneum for large myomas (≥8 cm) is hindered by several factors, such as the increased operative time, the risk of perioperative bleeding, and the risk of conversion to laparotomy. With the introduction of isobaric laparoscopy using abdominal wall lifting, this procedure can be performed using conventional surgical instruments introduced through small abdominal incisions. The aim of this study was to evaluate the feasibility, reproducibility, and safety of isobaric laparoscopic myomectomy for very large myomas ≥10 cm using a subcutaneous abdominal wall-lifting device.
A series of 24 consecutive patients with at least 1 symptomatic myoma ≥10 cm underwent a gasless laparoscopic myomectomy with the Laparotenser device. Conventional long laparotomy instruments were used.
Gasless laparoscopic myomectomy was successful in all 24 consecutive patients. The size of the dominant myoma varied from 10 cm to 20 cm. The median operating time was 93 minutes. The median postoperative drop in hemoglobin was 2.8 g/dL. No surgical complications occurred. The median hospital stay was 2.8 days.
Gasless laparoscopic myomectomy is feasible, reproducible, and safe for removing very large myomas. Therefore, it can represent an excellent option for the minimally invasive removal of very large myomas.
PMCID: PMC3015631  PMID: 16381362
Very large myomas; Isobaric gasless laparoscopy; Myomectomy; Subcutaneous abdominal wall lifting device
17.  Pulmonary embolus arising from sloughed off myoma in late puerperium 
Pulmonary embolus is a rare and serious complication of myoma uteri in the puerperium that resulted in late postpartum hysterectomy A 38-year-old, multiparous woman with a large myoma located on the left lateral wall of the uterus underwent emergency cesarean section due to fetal distres at 28 weeks. During the operation, a 15 cm sized intramural myoma was left without any intervention. On the 40th day postpartum the patient returned to the clinic with sepsis and pulmonary embolus because of obstruction of lochia drainage by the sloughed off myoma. The patient underwent hysterectomy and medical therapy for pulmonary embolus.
We presented an unusual complication of uterine leiomyoma in the late postpartum period after cesarean section. Whatever the mode of sloughing off of the myoma, the results of the obstruction of lochia drainage may be devastating as in our case. To avoid these complications, clinicians must be aware of these symptoms and prompt intervention is essential.
PMCID: PMC3939226  PMID: 24591925
Myoma uteri; pregnancy; puerperium; pulmonary embolus; sepsis
18.  Virtual Reality Uterine Resectoscopic Simulator: Face and Construct Validation and Comparative Evaluation in an Educational Environment 
This pilot study suggests that virtual reality resectoscopic systems have the potential to measure and improve the technical skills of novices before they operate on human patients.
Background and Objectives:
Recognizing that resectoscopic simulation may have an educational role, this pilot study was designed to evaluate the face validity and educational utility of a virtual reality uterine resectoscope training system.
A pilot prospective comparative study of novice and expert hysteroscopists' performance on a targeting exercise and myomectomy with the virtual loop electrode. At baseline, expert and novice resectoscopists each performed both exercises. Following instruction, novices practiced each exercise a total of 9 times with the 10th recorded as the training outcome. Results were compared both to baseline and to those of the experts. Data were analyzed with the paired t and Wilcoxon rank sum tests as appropriate.
At baseline, all experts touched 4 targets in a mean of 33 seconds with no perforations, compared to a mean of 2 for the 11 novices in a mean of 57 seconds (P=0.0034) with one perforation. In 3 minutes, the experts removed a mean of 97.3% of the virtual myoma, compared to 66.1% for the novices (P=0.0153). On the 10th “run,” novices touched a mean of 4 targets in a mean of 23 seconds, an improvement from baseline (P=0.0004) and improved to 89% on the myoma resection exercise (P=0.0515) 36.3% over baseline.
Although this pilot study has a relatively small sample size and represents the results at one institution, it demonstrates that virtual reality resectoscopic systems have the potential to measure and improve the technical skills of novices before they operate on human patients.
PMCID: PMC3148859  PMID: 21902963
Resectoscope; Hysteroscope; Virtual reality; Simulator
19.  Laparoscopic Radiofrequency Fibroid Ablation: Phase II and Phase III Results 
Background and Objectives:
To review phase II and phase III treatments of symptomatic uterine fibroids (myomas) using laparoscopic radiofrequency volumetric thermal ablation (RFVTA).
We performed a retrospective, multicenter clinical analysis of 206 consecutive cases of ultrasound-guided laparoscopic RFVTA of symptomatic myomas conducted on an outpatient basis under two phase II studies at 2 sites (n = 69) and one phase III study at 11 sites (n = 137). Descriptive and exploratory, general trend, and matched-pair analyses were applied.
From baseline to 12 months in the phase II study, the mean transformed symptom severity scores improved from 53.9 to 8.8 (P < .001) (n = 57), health-related quality-of-life scores improved from 48.5 to 92.0 (P < .001) (n = 57), and mean uterine volume decreased from 204.4 cm3 to 151.4 cm3 (P = .008) (n = 58). Patients missed a median of 4 days of work (range, 2–10 days). The rate of possible device-related adverse events was 1.4% (1 of 69). In the phase III study, approximately 98% of patients were assessed at 12 months, and their transformed symptom severity scores, health-related quality-of-life scores, mean decrease in uterine volume, and mean menstrual bleeding reduction were also significant. Patients in phase III missed a median of 5 days of work (range, 1–29 days). The rate of periprocedural device-related adverse events was 3.5% (5 of 137). Despite the enrollment requirement for patients in both phases to have completed childbearing, 4 pregnancies occurred within the first year after treatment.
RFVTA does not require any uterine incisions and provides a uterine-sparing procedure with rapid recovery, significant reduction in uterine size, significant reduction or elimination of myoma symptoms, and significant improvement in quality of life.
PMCID: PMC4035627  PMID: 24960480
Radiofrequency ablation; Laparoscopy; Laparoscopic ultrasound; Fibroid; Myoma
20.  Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors: Correlation to Mucin-1 and Galectin-3 Expression 
Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has been described. Tyrosine phosphorylation is a key mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study was to evaluate the phosphorylation of epithelial growth factor-receptor (EGFR) in normal myometrium, uterine myomas and uterine leiomyosarcomas. Formalin-fixed paraffin-embedded tissue samples from normal myometrium, leiomyomas and leiomyosarcomas were studied. Samples were immunohistochemically (IHC) assessed using the anti-EGFR phosphorylation of Y845 (pEGFR-Y845) and anti-pEGFR-Y1173 phosphorylation-specific antibodies. IHC staining was evaluated using a semiquantitative score. The expression of pEGFR-Y845 was significantly upregulated in leiomyosarcomas (p < 0.001) compared to leiomyomas and normal myometrium. In contrast, pEGFR-Y1173 did not differ significantly between the three groups of the study. Correlation analysis revealed an overall positive correlation between pEGFR Y845 and mucin 1 (MUC1). Further subgroup analysis within the tumoral group (myomas and leiomyosarcomas) revealed an additional negative correlation between pEGFR Y845 and galectin-3 (gal-3) staining. On the contrary no significant correlation was noted within the non-tumoral group. An upregulated EGFR phosphorylation of Y845 in leiomyosarcomas compared to leiomyomas implicates EGFR activation at this special receptor site. Due to these pEGFR-Y845 variations, it can be postulated that MUC1 interacts with it, whereas gal-3 seems to be cleaved from Y845 phosphorylated EGFR. Further research on this field could focus on differences in EGFR pathways as a potentially advantageous diagnostic tool for investigation of benign and malignant signal transduction processes.
PMCID: PMC3634430  PMID: 23449029
myometrium; leiomyoma; leiomyosarcoma; phosphorylation; EGFR; tyrosine kinase
21.  Developments in Techniques for Laparoscopic Myomectomy 
Conflicting opinions about laparoscopic myomectomy (LM) are still present regarding indications and risks related to reproductive outcome. We reviewed our 13-year experience (1) to identify risk factors or changes in methods that have improved our myomectomy technique and (2) to evaluate how the learning curve and improved surgical devices influenced our procedures, and (3) to study the myomectomy scar with a power color Doppler ultrasound (US).
From January 1991 to December 2003, we studied 332 patients who underwent laparoscopic myomectomy. We analyzed, as the learning curve, how the introduction of the Steiner morcellator, the use of vasoconstrictive agents, and different techniques of suturing have influenced parameters such as operating time and blood loss.
We performed 332 single or multiple myomectomies for symptomatic myomas. Most patients (47%) had more than one myoma, with a maximum of 8 per patient (average myomas removed for patients: 2.23, range 1 to 8). Myoma size ranged from 1cm to 20 cm (mean, 60.20±SD27.1 mm). Myomas <4cm were removed during myomectomy for larger ones. The conversion rate to laparotomy was 1.51%. The average drop in hemoglobin concentration was 1.06±SD0.86 g/100 mL (range, 0.7 to 2.2 g/100 mL). No blood transfusions were required. No major intraoperative complications occurred. The duration of the procedure ranged from 30 minutes to 360 minutes (mean, 124±SD52.6). The dimensions of the myomas removed increased with experience (4.91±SD2.2 cm of the earlier cases to 6.76±SD2.7 of the latest group, P<0.000). The learning curve positively influenced the length of the procedures in the first cases. The introduction of electromechanical morcellation in 1996 reduced the procedure time. Data showed significantly reduced Hb drop after the introduction in 1998 of vasoconstrictive agents (ΔHb 1.62 g/100 mL versus 0.95; P<0.001). The running suture offered few advantages in terms of procedure time. However, the drop in hemoglobin was advantageous (ΔHb 1.1 g/100mL vs 0.61, P<0.01). The overall rate of intrauterine pregnancy following LM was 65.5%. No uterine ruptures occurred. We had 2 serious postoperative complications:
With increased experience, the technical improvements and clinical results have changed our approach and decision making regarding laparoscopic myomectomy. Our results and extremely low conversion rate suggest that laparoscopic myomectomy is a safe and reliable procedure even in the presence of multiple or enlarged myomas.
PMCID: PMC3015797  PMID: 17651554
Laparoscopic myomectomy; Morcellator; Learning curve; Vasoconstrictive agents
22.  Laparoscopic Management of Adnexal Masses 
Background and Objective:
Although laparoscopic surgery for removal of adnexal masses is common, controversy exists about the safety and efficacy of this procedure for patients with malignancies. The aim of this study was to evaluate the effectiveness and safety of laparoscopic surgical treatment for patients with adnexal masses.
This was a retrospective chart review of one surgeon's experience in managing patients diagnosed with adnexal masses at 2 urban referral teaching hospitals in New York City. We reviewed the charts for 100 consecutive patients who underwent operative laparoscopy for management of adnexal masses between March 4, 1996 and November 9, 1998. Conversion to laparotomy, malignancy rate, complications, length of stay, and blood loss were recorded for each patient.
Laparoscopic management was successfully completed for 81 of the 100 patients in this study; however, 19 required conversion to laparotomy. All 81 patients managed laparoscopically had a benign diagnosis, whereas 7 of the 19 patients who underwent laparotomy were diagnosed with malignancy. The median length of stay, estimated blood loss, and operating room time were significantly lower for those treated by laparoscopy alone compared with those converted to laparotomy (2 vs. 7 days; 100 vs. 500 ccs; 130 vs. 235 minutes, respectively; P < 0.05). Though few patients were in the laparotomy group, that data are presented for completeness. A total of 10 complications occurred, 4 in the group of patients managed laparoscopically (2 enterotomies, 1 pneumothorax, and 1 vaginal cuff cellulitis). Six complications occurred in those managed with laparotomy (2 enterotomies, 2 wound infections, 1 pneumonia, and 1 postoperative fever). The indications for conversion to laparotomy were: 7 malignancies (5 ovarian cancers and 2 uterine cancers), 7 dense adhesions, 2 small bowel enterotomies, 1 intraoperative bleeding, 1 secondary to a large uterus (880 grams), and 1 secondary to a large myoma (13 cm x 14.5 cm x 6 cm).
The laparoscopic approach is effective and safe for managing patients with adnexal masses of unknown pathology. Malignancies can be diagnosed accurately, converted to laparotomy, and staged appropriately. Adequate surgical skills along with timely use of frozen sections are required for successful operative management.
PMCID: PMC3015439  PMID: 11394427
Adnexal diseases-diagnosis-surgery; Laparoscopy; Adnexal mass; Ovarian carcinoma
23.  Factors Influencing Endometrial Thickness in Postmenopausal Women 
Cut-off values for endometrial thickness (ET) in asymptomatic postmenopausal woman have been standardized. However, there are no comprehensive studies to document how various factors can influence the ET after the age of menopause.
To study the various factors influencing the ET in postmenopausal women.
Subjects and Methods:
This was a prospective observational study. A total of 110 postmenopausal women underwent detailed history taking, clinical examination, and transvaginal scan for uterine volume and ovarian volume. The volumes were calculated by using ellipsoid formula: Width × thickness × height × 0.523. The variation in ET with respect to the influencing factors such as age, duration of menopause, parity, body mass index (BMI), medical illness like diabetes/hypertension, drugs like tamoxifen, presence of myoma, uterine volume, ovarian volume, and serum estradiol (in selected patients) were measured. Descriptive analysis was performed using SPSS software (version 16, Chicago II, USA) to obtain mean, standard deviation (SD), 95% confidence intervals (CIs) and inter quartile ranges. Comparison of means was carried out using analysis of variance.
The mean (SD) age of the patients was 55.4 (6.91) years (95% CI, 54.1, 56.7). The mean (SD) age at menopause was 47.95 (3.90) years (95% CI, 47.2, 48.7) and the mean (SD) duration of menopause was 7.27 (6.65) years (95% CI, 6.01, 8.53). The mean (SD) ET was 3.8 (2.3) mm (95% CI, 3.36, 4.23). Medical illness like diabetes and hypertension did not alter the ET. ET increased as BMI increased and it was statistically significant. The presence of myoma increased uterine volume significantly and was associated with thick endometrial stripe. Similarly, whenever the ovaries were visualized and as the ovarian volume increased, there was an increase in ET. When ET was > 4 mm (n = 37), they were offered endocel, of which 16 agreed to undergo the procedure. None were found to have endometrial cancer.
This study suggests that parity, BMI, presence of myoma, tamoxifen usage, uterine volume, ovarian volume and serum estradiol influence the ET in postmenopausal women.
PMCID: PMC4160690  PMID: 25221714
Diabetes; Endometrial thickness; Hypertension; Ovarian and uterine volume; Postmenopause
24.  Caveolin-1 accumulation in the tongue cancer tumor microenvironment is significantly associated with poor prognosis: an in-vivo and in-vitro study 
BMC Cancer  2015;15:25.
Caveolin-1 (CAV1) may be upregulated by hypoxia and acts in a tumor-dependent manner. We investigated CAV1 in tongue squamous cell carcinoma (TSCC) and its association with clinical outcomes, and studied in vitro possible ways for CAV1 accumulation in the tumor microenvironment (TME).
TSCC cases (N = 64) were immunohistochemically stained for CAV1. Scores were separately assessed in the tumor and TME and plotted for association with recurrence and survival (univariate analysis with log-rank test). In vitro studies were performed on a 3D myoma organotypic model, a mimicker of TME. Prior to monoculturing HSC-3 tongue cancer cells, the model underwent modifications in oxygenation level (1%O2 hypoxia to upregulate CAV1) and/or in the amount of natural soluble factors [deleted by 14-day rinsing (rinsed myoma, RM), to allow only HSC-3-derived factors to act]. Controls included normoxia (21%O2) and naturally occurring soluble factors (intact myoma, IM). HSC-3 cells were also co-cultured with CaDEC12 cells (fibroblasts exposed to human tongue cancer). CAV1 expression and cellular distribution were examined in different cellular components in hypoxic and rinsed myoma assays. Twist served as a marker for the process of epithelial-mesenchymal transition (EMT). Exosomes isolated from HSC-3 media were investigated for containing CAV1.
Expression of CAV1 in TSCC had a higher score in TME than in the tumor cells and a negative impact on recurrence (p = 0.01) and survival (p = 0.003). Monocultures of HSC-3 revealed expression of CAV1 mainly in the TME-like myoma assay, similar to TSCC. CAV1+, alpha-smooth muscle actin (αSMA) + and Twist + CAF-like cells were observed surrounding the invading HSC-3, possibly reflecting EMT. RM findings were similar to IM, inferring action of HSC-3 derived factors, and no differences were seen when hypoxia was induced. HSC-3-CaDEC12 co-cultures revealed CAV1+, αSMA+ and cytokeratin-negative CAF-like cells, raising the possibility of CaDEC12 cells gaining a CAF phenotype. HSC-3-derived exosomes were loaded with CAV1.
Accumulation of CAV1-TME in TSCC had a negative prognostic value. In vitro studies showed the presence of CAV1 in cancer cells undergoing EMT and in fibroblasts undergoing trans-differentiation to CAFs. CAV1 delivery to the TME involved cancer cell-derived exosomes.
PMCID: PMC4318139  PMID: 25633184
Tongue cancer; Caveolin-1; Survival; Myoma organotypic model; Tumor microenvironment; Cancer-associated fibroblasts; Exosomes; Epithelial-mesenchymal transition
25.  Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas 
BioMed Research International  2014;2014:521313.
In this study the expression of GnRH, FSH, LH, ER-α, ER-β, and PR receptors was examined in uterine myomas of women in reproductive and perimenopausal age. In cases of GnRH and tropic hormones a membranous and cytoplasmic immunohistochemical reaction was detected, in cases of ER-α and PR the reaction was located in cell nucleus, and in the case of ER-β it manifested also a cytoplasmic location. In some of the examined cases the expression was detected in endometrium, myocytes, and endothelium of blood vessels, in uterine glands and myoma cells. In myometrium the level of GnRH and LH receptors increases with age, whereas the level of progesterone and both estrogen receptors decreases. In myomas of women in reproductive age, independently of their size, expression of GnRH, FSH, and LH receptors was more pronounced than in myometrium. In women of perimenopausal age, independently of myoma size, expression of LH and estrogen α receptors was higher while expression of GnRH receptors was lower than in myometrium. FSH receptor expression was not observed. Expression of estrogen receptor β was not affected by age of the woman or size of myoma. Analysis of obtained results indicates on existing in small myomas local feedback axis between GnRH-LH-progesterone.
PMCID: PMC4090522  PMID: 25050358

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