Identifcation of up-regulated genes in human uterine leiomyoma by sup-pression subtractive hybridization

In searching for differentially expressed genes in human uterine leiomyomas (ULs), suppression sub-tractive hybridization was used to construct an UL up-regulated library, which turned out to represent 88genes. After two rounds of screening by reverse Northern analysis, twenty genes were proved to be up-regulated, including seventeen known genes and three genes with unknown function. All these genes werefirstly associated with UL. Three genes with notable difference were selected for Northern confirmationOur results proved the authenticity of the twenty genes. One gene named Phospholipase A2 (PLA2) showedup-regulation in 4/6 of the patients and investigation of tissue distribution indicated that it had obviousexpression in prostate, testis, liver, heart and skeletal muscle.

Uterine artery embolization combined with percutaneous microwave ablation for the treatment of prolapsed uterine submucosal leiomyoma:A case report

BACKGROUND Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia.However,an alternative treatment approach is needed for patients who cannot tolerate general anesthesia.We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia.CASE SUMMARY A 46-year-old female suffered from abnormal uterine bleeding,severe anemia,and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma.She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency.A new individualized combined treatment,consisting uterine artery embolization(UAE),percutaneous microwave ablation(PMWA)of the pedicle and the endometrium,and transvaginal removal of the leiomyoma by twisting,was performed.The lesion was completely removed successfully under local anesthesia without any major complications.The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life.CONCLUSION UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.

Cystic Degeneration of Uterine Leiomyoma Misdiagnosed as Ovarian Malignancy: A Case Report

Background: Massive cystic degeneration of the uterine myoma might mimic an ovarian tumor, especially a malignant ovarian tumor, causing misdiagnosis. We present a case of a woman with marked cystic degeneration of a uterine leiomyoma mimicking an ovarian neoplasm. Case: A 65-year-old woman (gravida 6, para 6) visited us due to an abdominal tumor. Clinical examination and radiology exploration suggested the presence of an ovarian tumour. The patient underwent a total abdominal hysterectomy with bilateral adnexectomy. Histopathology confirmed a final diagnosis of a degenerated leiomyoma. The patient’s postoperative course was uneventful and she was discharged on her 5th post-operative day. Conclusions: When a patient has a huge abdomino-pelvic mass, mimicking an ovarian tumor, cystic degeneration of uterine myoma should be considered as a differential diagnosis.

Effects of curcumin on uterine leiomyoma in a rat model by inhibiting β-catenin/Wnt signaling pathway

Background:Women with uterine leiomyomas may suffer severe symptoms.To avoid risks of side effects,it is necessary to develop an optimal agent to shrink leiomyomas with fewer side effects and a lower recurrence rate.Curcumin may have a lower side effect in uterine leiomyoma treatment.Methods:We established the estrogen-and-progesterone-induced murine model of uterine leiomyoma.Next,we determined the expression of related genes of the β-catenin/Wnt signaling pathway by western blot,reverse transcription-polymerase chain reaction,and immunohistochemistry.We also noticed the morphological changes in uterine tissues by hematoxylin-eosin staining.Results:Curcumin plays an important role in Wnt/β-catenin signaling pathway-related expression including β-catenin,adenomatous polyposis coli,glycogen synthase kinase-3β,Wnt-11,and serum hormone concentrations.Conclusions:Curcumin could the down-regulation of serum hormone concentrations and inhibition of the β-catenin/Wnt signaling pathway in the treatment of uterine leiomyoma.

Diffuse uterine leiomyomatosis: A case report and review of literature

BACKGROUND Diffuse uterine leiomyomatosis(DUL)is a benign uterine smooth muscle neoplasm with unknown etiology.Since DUL is rarely reported,knowledge regarding it is limited.The rate of early diagnosis is low,and DUL is often misdiagnosed as common multiple uterine leiomyomas before surgery.CASE SUMMARY A 27-year-old patient with no sexual activity presented to the Emergency Department of our hospital complaining of heavy vaginal bleeding.She had a history of uterine fibroids and menorrhagia.Pelvic examination showed a regularly enlarged uterus,similar in size to that associated with a 4-mo pregnancy.Pelvic magnetic resonance imaging(MRI)revealed numerous multiple uterine fibroids,and a transabdominal myomectomy(TM)was performed.Intraoperative exploration revealed that the myometrium was full of myoma nodules of variable sizes.Over 50 leiomyomas were removed.The pathology report confirmed leiomyoma.The patient was discharged and received a gonadotropin-releasing hormone analog(3.75 mg)for 6 mo.Ten months after surgery,the patient presented to the hospital again for abnormal uterine bleeding.MRI showed an irregular mass with a diameter of 5.2 cm without sharp demarcation in the uterine cavity.Submucosal leiomyoma was considered first,and the patient underwent a hysteroscopic myomectomy plus hymen repair.Intraoperative exploration showed that there were several leiomyomatosis masses in the cavity.Postoperative pathological exam-ination confirmed submucosal leiomyoma and necrotic and generative tissue.Although the menstrual cycle was still irregular,the patient did not have symptoms of menorrhagia for a period of 28 mo after the second surgery.CONCLUSION Individuals with DUL are easily misdiagnosed due to the lack of specific manifestations of this disease.MRI is helpful for early identification and preoperative evaluation.There is currently no unified method of diagnosis.For women who want to preserve fertility,conservative surgery should be made an option.When TM is chosen,a modified new myomectomy should be considered to avoid the drawbacks of traditional TM.

A Case Report on Pulmonary Benign Metastasizing Leiomyoma with Recurrent Uterine Fibroids

Pulmonary benign metastasizing leiomyoma(PBML)is a type of benign metastasizing leiomyoma(BML),which metastasizes to lungs.In view of the rarity and nonspecific imaging characteristics of PBML,this condition is easily misdiagnosed as malignant lung cancer.This is a case report of a 39-year-old lady in whom multiple bilateral lung nodules were found during a health checkup and was diagnosed with PBML.The patient had recurrent uterine fibroids and underwent myomectomy twice,7 years and 3 years ago,respectively,before the diagnosis of PBML was made.This patient was asymptomatic,and regular examinations were normal.Her laboratory investigations were all within normal range.Computed tomography(CT)showed multiple nodules in bilateral lungs.In order to confirm the disease,thoracoscopic nodule resection and tissue biopsy were performed.Hematoxylin eosin(HE)staining showed spindle-shaped cells,while immunohistochemical staining revealed positive for desmin,smooth muscle actin(SMA),estrogen receptor(ER),and progesterone receptor(PR),which are all PBML markers.The patient was followed-up without any further treatment.After 8 months of follow-up,CT scan revealed an increased number of nodules.This is unique case because of the recurrence of uterine fibroids,which means that the patient is susceptible to it.Our report may give a new insight to the relationship between the susceptibility of uterine fibroids and the onset and progression of PBML.

Role of epidermal growth factor in pathogenesis of uterine leiomyomas

Objective:To investigate the role of epidermal growth factor(EGF) in the pathogenesis of uterine leiomyomas.Methods:Human myometrial smooth muscle cells(HM-SMCs) and smooth muscle cells of human uterine leiomyomas(HL-SMCs) were separated from patients' specimens and cultured.After processed by EGF or PD98059(inhibitor of MKK/MEK) +EGF,the proliferation rate of both SMCs was detected by BrdU method and the phosphorylation level of p44/42 mitogen-activated protein kinase(MAPK) was determined by Western-blot.After different processing time by EGF,the phosphorylation levels of p44/42 MAPK and AKT and p27 expression level in both SMCs were detected by Western-blot.Results:EGF could significantly promote HL-SMCs proliferation and PD98059 could inhibit this effect(P<0.05);besides,PD98059 could inhibit the increase of the phosphorylation level of p44/42 MAPK in both SMCs induced by EGF.When the processing time by EGF was over 15 min,the phosphorylation levels of p44/42 MAPK and AKT in both SMCs decreased sharply and were close to zero:p27 expression in HM-SMCs raised significantly while the upregulation in HL-SMCs was little.Conclusions:EGF could not cause activation of EGFR because of the dephosphorylation of p44/42 MAPK and AKT in HL-SMCs,which caused p27 expression insufficiently and cell cycle dysregulation.

Investigation of amyloid deposition in uterine leiomyoma patients

Objects: To investigate the pathogenesis of amyloid presented in uterine leiomyoma. Methods: 36 uterine leiomyoma patients were recruited and divided into two groups according to Congo red staining results. 6 cases are Congo red staining-positive, and 30 cases Congo red staining-negative which represented amyloid positive and amyloid negative respectively. All patients’ serum total protein (TP), albumin (Alb) and prealbumin (PA) levels were measured as well as blood hemoglobin (Hb), cell counts of white blood cell (WBC), neutrophils (NEU) and lymphocyte (LYM). Glycogen in tissue was compared between amyloid accumulated and amyloid negative sections with periodic acid schiff staining (PAS) in leiomyoma patients. Results: All of blood Hb concentration, WBC, NEU and LYM have not been found significant differences between two groups. Also no obvious infiltration of inflammatory cells was observed in tissue with amyloid deposition in uterine leiomyoma patients. And levels of TP, Alb and prealbumin have not been found significant differences between two groups. The amyloid was negative in leiomyoma entity cells range by Congo red staining, while small blood vessels in myoma tissues were positively detected with high rate. Amyloid was found in normal tissue around myoma as well as in blood vessel of pseudo-capsule. Increased PAS-positive material induced by leiomyoma was not correlated with amyloid deposition. Conclusions: Metabolic changes in the setting of functional alterations of cell in local microenvironment with uterine leiomyoma, may be related to the amyloid deposition.

Study of 41 Cases of Pregnancy after Uterine Leiomyoma Treatment by Uterine Artery Embolization (UAE)

Uterine leiomyoma, a benign tumor, may be treated with hormone therapy, conventional surgical resection and uterine artery embolization (UAE): this paper reports the study on safety after UAE treatment. Pregnancy processes and prognoses of a total of 41 cases from 39 patients (two women were pregnant twice) who succeeded to pregnancy after UAE treatment in our clinic were studied. The average age of patients was 34.5 (29 - 40). Patients included 24 cases of multiple uterine leiomyoma and 14 cases of solitary leiomyoma;the average size of leiomyoma was 388.3 cm3 (15 - 1059 cm3) and the average period between UAE operation and pregnancy was 26.5 months (1 - 120). Causes of pregnancy were 29 cases of natural pregnancy and 12 cases of infertility treatment: 28 cases succeeded in delivery, 7 cases resulted in spontaneous abortion, and 6 cases are ongoing. Premature birth, placental abnormality and low-weight babies were observed in 3, 3, and 1 cases, respectively;the latter 1 case was of triplets. Although the incidence of placental abnormality was a little high, no other serious complications were observed, suggesting that pregnancy after UAE has no problem from the obstetric point of view. In the future, UAE is considered to be worthwhile if carefully done for cases who want to become pregnant.

Birth outcomes and pregnancy complications of women with uterine leiomyoma—a population-based case-control study

Objective Uterine leiomyoma is not a rare pathological condition in pregnant women;thus the aim of the study was to evaluate the recent progress in the treatment of these pregnant women on the basis of the association of leiomyoma in pregnancy (LP) with pregnancy complications and birth outcomes including structural birth defects, i.e. congenital abnormalities (CA) in the offspring. Design Cases with CA and matched controls without CA in the population-based Hungarian Case-Control Surveillan- ce System of Congenital Abnormalities (HCC SCA) were evaluated. Only women with prospectively and medically recorded LP in prenatal maternity logbook and medically recorded birth outcomes (gestational age, birth weight, CA) were included to the study. Setting the HCCSCA, 1980-1996 contained 22,843 cases with CA and 38,151 matched controls without CA. Population Hungarian pregnant women and their informative offspring: live births, stillbirths and prenatally diagnosed malformed fetuses. Methods Comparison of birth outcomes of ca- ses with matched controls and pregnancy com- plications of pregnant women with or without LP. Main outcome measures Pregnancy complications, mean gestational age at delivery and birth weight, rate of preterm birth, low birthweight, CA. Results A total of 34 (0.15%) cases had mothers with LP compared to 71 (0.19%) controls. There was a higher incidence of threatened abortion, placental disorders, mainly abruption placentae and anaemia in mothers with LP. There was no significantly higher rate of preterm birth in the newborns of women with LP but their mean birth weight was higher and it associated with a higher rate of large birthweight newborns. A higher risk of total CA was not found in cases born to mothers with LP (adjusted OR with 95% CI = 0.7, 0.5-1.1), the spe- cified groups of CAs were also assessed versus controls, but a higher occurrence of women with LP was not revealed in any CA group. Con- clusions Women with LP have a higher risk of threatened abortion, placental disorders and anaemia, but a higher rate of adverse birth outcomes including CAs was not found in their offspring.

Spontaneous Uterine Perforation Secondary to Leiomyosarcoma Arising in a Uterine Leiomyoma

Histogenesis of uterine leiomyosarcoma has been controversial. It is generally believed that uterine leiomyosarcomas arise de novo, rather than from any precursor lesions. We report an unusual case of spontaneous rupture of leiomyosarcoma arising in pre-existing calcified uterine leiomyoma, which has been monitored over the years after menopause. This case also suggests that spontaneous intraperitoneal hemorrhage associated with malignant transformation of uterine leiomyoma, although rare, should be considered in postmenopausal women presenting with rapid growing uterine mass.

Recurrent atypical leiomyoma in bladder trigone,confused with uterine fibroids:A case report

BACKGROUND Tumors originating from the posterior bladder wall can be challenging to diagnose because they may mimic a mass from the uterine cervix.Atypical leiomyoma of the bladder trigone is extremely rare,with few reported cases,and requires caution during surgery to avoid damage to the adjacent ureter.Diagnostic surgery and confirmational pathology are essential to assess whether the tumor is malignant and relieve clinical symptoms.Herein,we describe a case of recurrent leiomyoma with focal atypia in the bladder trigone.CASE SUMMARY A 29-year-old woman with a uterine fibroid incidentally found at a regular checkup was referred to our hospital.Based on magnetic resonance imaging,either urinary bladder leiomyoma or protrusion of pedunculated uterine cervical fibroid into the bladder was suspected.This leiomyoma in the trigone of the bladder was completely excised by laparotomy,and the patient was discharged without complication.Follow-up outpatient ultrasonography identified tumor recurrence after four years.As focal atypia was identified previously,laparotomy was performed to confirm the pathology.A round solid mass was resected from the posterior bladder wall without injuring either ureteric orifice.This tumor was pathologically diagnosed as a leiomyoma without atypia.Three-year follow-up ultrasonography has revealed no recurrence.CONCLUSION Atypical leiomyoma in bladder trigone is rare and could be easily mistaken for fibroid in the uterine cervix.To confirm histopathology,surgical excision is mandatory and regular follow-up is necessary to detect recurrence.

A Systematic Review on Efficacy and Safety of Gasless Laparoscopy in the Management of Uterine Leiomyoma

Uterine leiomyoma causes considerable morbidity in women. This study systematically reviewed the efficacy and safety of gasless laparoscopic myomectomy(GLM) in the management of uterine leiomyoma by comparing GLM with other minimally invasive procedures. Cochrane Library, PubMed, EMBASE, Web of Science, WANFANG database and China National Knowledge Infrastructure(CNKI) were searched for studies published in English or Chinese between January 1995 and May 2015, and related references were traced. Study outcomes from randomized controlled trials and retrospective cohort studies were presented as mean difference(MD) or odds ratio(OR) with a 95% confidence interval(CI). Seventeen studies(including 1862 patients) meeting the inclusion criteria, including 934 treated with GLM and 928 treated with other minimally invasive procedures were reviewed. The results of meta-analysis revealed that GLM resulted in significantly shorter operating time [MD=–10.34, 95% CI(–18.12, –2.56), P<0.00001], shorter hospital stay [MD=–0.47, 95% CI(–0.88, –0.06)], less time to flatus [MD=–2.04, 95% CI(–2.59, –1.48)], less postoperative complications [OR=0.20, 95% CI(0.06, 0.62)] and less blood loss [MD =–30.74, 95% CI(–47.50, –13.98)]. On the other hand, there were no significant differences in duration of post-operative fever [MD=–0.52, 95% CI(–1.46, 0.42)] between the two groups. Additionally, GLM was associated with lower febrile morbidity, lower postoperative abdominal pain, and higher postoperative hemoglobin than other minimally invasive procedures for the treatment of uterine leiomyoma. In conclusion, GLM and other minimally invasive procedures are feasible, safe, and reliable for uterine leiomyoma treatment. However, available studies show that GLM is more effective and safer than other minimally invasive approaches.

Identifcation of up-regulated genes in human uterine leiomyoma by sup-pression subtractive hybridization

In searching for differentially expressed genes in human uterine leiomyomas (ULs), suppression sub-tractive hybridization was used to construct an UL up-regulated library, which turned out to represent 88genes. After two rounds of screening by reverse Northern analysis, twenty genes were proved to be up-regulated, including seventeen known genes and three genes with unknown function. All these genes werefirstly associated with UL. Three genes with notable difference were selected for Northern confirmationOur results proved the authenticity of the twenty genes. One gene named Phospholipase A2 (PLA2) showedup-regulation in 4/6 of the patients and investigation of tissue distribution indicated that it had obviousexpression in prostate, testis, liver, heart and skeletal muscle.

Identification of differentially expressed genes in human uterine leiomyomas using differential display

In searching of differentially expressed genes in human uterine leiomyomas, differential display was used with twelve pairs of primers to compare human uterine leiomyomas with matched myometrium. False positives were eliminated by reverse Northern analysis. Positives were confirmed by Northern blot analysis. RESULTS: [1] Four of 69 cDNA fragments (3 up-regulated named L1, L2 and L3 and 1 down-regulated named Mi in leiomyoma) were confirmed by Northern analysis. [2] Sequence comparison and Northern analysis proved that Li is exactly the human ribosomal protein Si9. [3] It was present ubiquitously in i3 tissues tested but in various levels and even in different size. [4] Li was highly expressed in parotidean cystadenocarcinoma, pancreatic cancer and breast cancer examined. [5] No mutations have been found in human uterine leiomyomas (n=6). CONCLUSIONS: hRPSi9 overexpression might be a universal signal in rapid cell growth tissues.

IDENTIFICATION OF DIFFERENTIAL PROTEINS IN UTERINE LEIOMYOMA BY TWO-DIMENSIONAL ELECTROPHORESIS

Objective: To establish and optimize the two-demensional electrophoresis maps of uterine leiomyoma and to study the difference of global protein patterns between uterine leiomyoma and normal myometrium. Methods: Using Two-dimensional electrophoresis followed by computer-assisted image analysis, the differential proteins between uterine leiomyoma and normal myometrium were compared. Results: The well-resolved and reproducible two-dimensional gel electrophoresis patterns of uterine leiomyoma and normal myometrium were established. Totally 1085±108 and 1103±151 protein spots were obtained by using the pH 4-7 IPG strips in uterine leiomyoma and normal myometrium map, respectively, of which 7 spots increased and 15 spots decreased in quantity in uterine leiomyoma compared with normal myometrium. Conclusion: The differentially expressed proteins are useful for studying the mechanism of the cause of uterine leiomyoma.

Guinea Pig Model of Uterine Leiomyoma Established by Intragastric Administration of Estrogen

[Objective] The paper was to establish the guinea pig model of uterine leiomyoma by intragastric administration of estrogen and to dis-cuss the effect of different doses and administration cycles on formation of uterine leiomyoma. [Method] Mature female guinea pigs were divided into short term model group and long term model group, and intragastrically administrated with estradiol valerate at the dose of 0.1 mg/100 g body weight twice a week for 6 and 8 weeks respectively. Guinea pigs intragastrically administrated with equal volume of normal saline were set as con-trol. After 6 or 8 weeks, the guinea pigs were sacrificed. The serum levels of estrogen and progesterone were measured by ELISA and the leiomyoma formation rate was measured. Histological changes were compared between treatment group and control group with HE staining. [Results] The leiomyoma formation rate was 30% in short term model group and 40% in long term model group. The overall leiomyoma formation rate was 35%.The serum level of estrogen in model animals increased significantly and the progesterone level decreased in long term model group. Histopathologi-cal examination confirmed that the guinea pig model of uterine leiomyoma was established successfully. [Conclusions] Intragastric administration of estrogen is a simple and effective method for establishing guinea pigs model of uterine leiomyoma.

CLINICAL STUDY ON EFFECT OF TRIPTERYGIUM WILFORDII HOOK. F. GLYCOSIDES ON UTERINE LEIOMYOMA

To observe the therapeutic effect and side reactions of Tripterygium wilfordii Hook.f (GTW) glycosides on patients with uterine leiomyomas. Methods 65 normally cycling women with symptomatic uterine leiomyomas received 40mg daily dose GTW for 3 to 6 months. Baseline ultrasound tests were obtained to evaluate the sizes of myomas and uterus, then repeated three and six months after treatment. Blood samples were collected to determine the hormonal levels of in the mid-follicular and mid-luteal phases of the menstrual cycles before GTW therapy and at 3～4 months and 5～6 months after treatment. Results Significant decrease in leiomyoma volume was shown in 39 of 65 (60%) and 28 of 40 ( 70% ) patients after 3～4 months and 5～6 months of treatment, respectively. The decrease of the volume of leiomyoma was time-dependent as while 27. 84% and 51.60% in 3～4 months and 5～6months, respectively. 25 of 65 patients had amenorrhea during the course of treatment. Tripterygium wilfordii glycosides treatment induced a significant increase in LH and FSH levels (P <0. O1 ) as compared with pretreatment values, hi contrary, a significant decrease in E2 and P levels ( P <0. 05) was found, but no changes were observed in T and PRL levels after treatment. Conclusion Tripterygium wilfordii might serve as an effective therapeutic agent for leiomyomas with fewer side effects. A reversible inhibitory, effect on the ovary by Tripterygium wilfordii glycosides may be one of the mechanisms of Tripterygium wilfordii in decreasing leiomyoma volume.

Metastasis to a uterine leiomyoma originating from lung cancer: a case report

The uterus is an uncommon site of metastasis especially from a primary lung adenocarcinoma. More frequently, extragenital primary tumours, including lung cancer, metastasize to the ovaries. In the literature, lung cancer metastasizing to the uterus is rare and has been reported to involve the endometrium and uterine serosa. Here, we report an unusual case of a 58-yearold woman who had a history of lung adenocarcinoma with subsequent metastasis to a single uterine fibroid only. The patient was known to have a long history of asymptomatic fibroids. In 2008, she was diagnosed with lung adenocarcinoma which was treated with primary surgery and adjuvant chemotherapy. Four years later, a routine abdominal computerised tomography scan showed an enlargement of the fibroid and she underwent a hysterectomy and bilateral salpingooophorectomy. Pathology reported a lung adenocarcinoma metastatic to the uterine leiomyoma with a similar morphology to the original pulmonary malignancyand this was confirmed with immunohistochemical staining. She had no evidence of metastatic disease elsewhere. The final diagnosis was metastasis of a primary lung adenocarcinoma confined to a uterine leiomyoma. Our patient also fulfilled the criteria for a phenomenon called tumour-to-tumour metastasis in this case a primary malignancy having metastasized to a benign tumour. In conclusion, metastasis of a primary lung cancer to the female reproductive tract has been documented, but clinicians should also be aware that metastasis to benign gynaecological tumours such as fibroids can also occur, especially in the setting of tumour-to-tumour metastasis. In addition, the clinical history and use of immunohistochemistry are invaluable in reaching a diagnosis.

Evaluation of the Efficacy and Effectiveness of Hysteroscopic Electroresection in the Treatment of Submucosal Uterine Fibroids

Objective:To evaluate the effect of hysteroscopic electroresection in treating submucosal uterine fibroids.Methods:Using the random number table method,70 patients with submucosal uterine fibroids were divided into two groups,35 cases/group.The control group underwent laparoscopic myomectomy,and the observation group underwent hysteroscopic electroresection.Surgical indicators,sex hormone indicators,inflammation indicators,and treatment effects were compared between the two groups.Results:The surgical indicators,sex hormone indicators,and inflammatory indicators three months after operation in the observation group were all more ideal than those of the control group.The total effective rate of the observation group(97.14%)was higher than that of the control group(P<0.05).Conclusion:Hysteroscopic electroresection for the treatment of submucosal uterine fibroids was less invasive,accelerates recovery,and is more effective.