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Gynecologic and Obstetric Investigation 2019Ulipristal acetate ([UPA], Esmya®) is an orally active selective progesterone-receptor modulator that has been approved as preoperative treatment for uterine myomas....
BACKGROUND/AIMS
Ulipristal acetate ([UPA], Esmya®) is an orally active selective progesterone-receptor modulator that has been approved as preoperative treatment for uterine myomas. This systematic review aims to summarize the available data on surgical outcomes of patients undergoing myomectomy by hysteroscopy or by laparoscopy after preoperative treatment with UPA.
METHODS
this review was performed following PRISMA guidelines and was registered in PROSPERO (CRD42018092201). PubMed, EMBASE, and Medline databases were systematically searched electronically until March 2018 for keywords concerning this topic. There were included only peer-reviewed, English language journal articles.
RESULTS
two prospective studies and 4 retrospective studies were included. The effect of UPA on the endometrium does not increase the technical difficulty during hysteroscopic myomectomy, but it increases the chance of complete primary resection in complex hysteroscopic myomectomies. Moreover, UPA does not increase the overall technical difficulty of laparoscopic myomectomy. Contradictory results have been reported on the impact of UPA on the separation of the myoma from the myometrium and on the consistency of the myomas.
CONCLUSION
current results support the use of UPA prior to both surgical procedures. Further studies should confirm these preliminary findings and to assess the long-term outcomes of myomectomies following UPA treatment.
Topics: Adult; Endometrium; Female; Humans; Hysteroscopy; Laparoscopy; Leiomyoma; Middle Aged; Norpregnadienes; Preoperative Period; Prospective Studies; Retrospective Studies; Treatment Outcome; Uterine Myomectomy; Uterine Neoplasms
PubMed: 30554215
DOI: 10.1159/000495347 -
Turk Patoloji Dergisi 2018The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine...
OBJECTIVE
The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine clinical-pathological characteristics, treatment options and outcome.
MATERIAL AND METHOD
An electronic literature search was conducted from 1976 to 2018. After the comprehensive evaluation and conjunction with our case, the study included 79 cases.
RESULTS
The median age at initial diagnosis was 49 years (range; 16-86 years). The age was under 40 years in 21 (26.6%) patients. Whereas 68 patients underwent at least hysterectomy, 9 patients had organ sparing surgery. There was necrosis in 4 (5.1%) patients, atypia in 16 (20.3%) patients, and infiltrative tumor border in 34 (43%) patients. At least one mitosis per 10 high power fields was determined in 36 (45.5%) patients. The tumor involved at least part of the myometrium in 54 (68.3%) patients. Median follow-up time was 30 months (range; 3-296 months). Recurrence was determined in 5 (6.3%) patients. The disease free survival (DFS) was significantly related only to surgery type. None of the pathologic features were associated with DFS. The 5-year DFS was 86% and 96% in patients who underwent organ sparing surgery or not, respectively (p=0.038).
CONCLUSION
The accurate pathologic diagnosis of UTROSCT has great value in shaping surgical management and management during the follow-up period. Organ sparing surgery was related to poor DFS. Although recurrence is rare, it should be kept in mind for patients with UTROSCT.
Topics: Disease-Free Survival; Female; Humans; Hysterectomy; Middle Aged; Neoplasm Recurrence, Local; Organ Sparing Treatments; Sex Cord-Gonadal Stromal Tumors; Uterine Neoplasms
PubMed: 30421416
DOI: 10.5146/tjpath.2018.01429 -
European Journal of Obstetrics,... Nov 2018Microcystic, elongated, fragmented (MELF) pattern of myometrial invasion has been proposed as a prognostic marker in patients with endometrial carcinoma (EC). Its...
Microcystic, elongated, fragmented (MELF) pattern of myometrial invasion has been proposed as a prognostic marker in patients with endometrial carcinoma (EC). Its prognostic and predictive effect still remains elusive. The aim of the present study is to accumulate the current knowledge on the role of MELF pattern in the prognosis and survival of patients with EC. Medline, Scopus, Google Scholar, and Clinicaltrials.gov databases were searched for articles published up to May 2018, along with the references of all articles. Prospective and retrospective trials reporting outcomes of cases with EC who were examined for MELF pattern were considered eligible for inclusion in the present systematic review. Of the 196 records screened, 14 were considered eligible. A total of 14 studies which comprised 588 women were finally included in the present systematic review. All the included patients were evaluated for presence of MELF pattern of myometrial invasion. MELF positive (+) patients were more likely to present with larger and higher grade tumors, lymph node metastasis, lymphovascular invasion and >50% myometrial invasion. No difference was reported in disease free survival (DFS) and disease specific survival (DSS) as well as in vaginal recurrence rates. MELF (+) was reported as a significant indicator of survival. In conclusion, MELF pattern of myometrial invasion plays a critical role in lymphovascular space invasion and lymph node metastasis in patients with EC. Regardless, its implication in survival and recurrences is ill determined.
Topics: Aged; Carcinoma; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Myometrium; Neoplasm Invasiveness; Prognosis; Prospective Studies; Retrospective Studies; Risk Factors
PubMed: 30286364
DOI: 10.1016/j.ejogrb.2018.09.036 -
The Journal of Maternal-fetal &... Jun 2020Multiple factors and pathways have been reported as critical machineries for cell differentiation and survival during pregnancy; a number of them involve glycogen...
Multiple factors and pathways have been reported as critical machineries for cell differentiation and survival during pregnancy; a number of them involve glycogen synthase kinase (GSK) 3a/β. Several reports on GSK3's functional role exist; however, the specific role of GSK3 in reproductive tissues and its contribution to normal or abnormal parturition are still unclear. To fill this knowledge gap, a systematic review of literature was conducted to better understand the functional role of GSK3 in various intrauterine tissues during implantation, pregnancy, and parturition. We conducted a systematic review of literature on GSK3's expression and function reported between 1980 and 2017 in reproductive tissues during pregnancy using three electronic databases (Web of Science, Medline, and ClinicalTrials.gov). Study selection, data extraction, quality assessment and analyses were performed in duplicate by two independent reviewers. A total of 738 citations were identified; 80 were selected for full text evaluation and 25 were included for final review. GSK3's regulation and function were mostly studied in tissues and cells from placentas (12), fetuses (8), uteruses (6), and ovaries (2). GSK3 is primarily reported as a downstream responder of protein kinase B (AKT)-, Wnt-, and reactive oxygen species (ROS)-related pathways where it plays a critical role in cell survival and growth in reproductive tissues. Though GSK3 has been functionally linked to a number of biological processes in reproductive tissues, it has primarily been studied as a secondary signaler of various conserved cell signaling pathways. Lack of scientific rigor in studying GSK3's role in reproductive tissues makes this molecule's function still obscure. No studies have reported GSK3 in the cervix, and very few reports exist in myometrium and decidua. This systematic review suggests more functional and mechanistic studies focusing on GSK3 need to be conducted in reproductive biology.
Topics: Biomarkers; Female; Glycogen Synthase Kinase 3; Humans; Parturition; Pregnancy
PubMed: 30278798
DOI: 10.1080/14767058.2018.1531843 -
American Journal of Reproductive... Dec 2018Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is...
Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is unknown. Therefore, we conducted a systematic review of literature on p38 MAPK expression, activation, and function in reproductive tissues throughout pregnancy and parturition, published between January 1980 and August 2017, using four electronic databases (Web of Science, PubMed, Medline, and CoCHRANE). We identified 418 reports; 108 were selected for full-text evaluation and 74 were included in final review. p38 MAPK was investigated using feto-maternal primary or immortalized cells, tissue explants, and animal models. Western blot was most commonly used to report phosphorylated (active) p38 MAPK. Human placenta (27), chorioamniotic membranes (14), myometrium (13), decidua (8), and cervix (1) were the studied tissues. p38 MAPK's functions were tissue and gestational age dependent. Isoform specificity was hardly reported. p38 MAPK activity was induced by ROS or proinflammatory cytokines to promote cell signaling linked to cell fate, primed uterus, ripened cervix, and proinflammatory cytokine/chemokine production. In 35 years, reports on p38 MAPK's role during pregnancy and parturition are scarce and current literature is insufficient to provide a comprehensive description of p38 MAPK's mechanistic role during pregnancy and parturition.
Topics: Animals; Disease Models, Animal; Female; Gene Expression Regulation; Genitalia, Female; Humans; Inflammation; Oxidative Stress; Parturition; Pregnancy; Reproduction; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 30178469
DOI: 10.1111/aji.13047 -
International Journal of Molecular... Aug 2018Growing evidence supports a role of vitamin D (VD) in reproductive health. Vitamin D receptor (VDR) is expressed in the ovary, endometrium, and myometrium. The... (Review)
Review
Growing evidence supports a role of vitamin D (VD) in reproductive health. Vitamin D receptor (VDR) is expressed in the ovary, endometrium, and myometrium. The biological actions of VD in fertility and reproductive tissues have been investigated but mainly using animal models. Conversely, the molecular data addressing the mechanisms underlying VD action in the physiologic endometrium and in endometrial pathologies are still scant. Levels of VDR expression according to the menstrual cycle are yet to be definitively clarified, possibly being lower in the proliferative compared to the secretory phase and in mid-secretory compared to early secretory phase. Endometrial tissue also expresses the enzymes involved in the metabolism of VD. The potential anti-proliferative and anti-inflammatory effects of VD for the treatment of endometriosis have been investigated in recent years. Treatment of ectopic endometrial cells with 1,25(OH)₂D₃ could significantly reduce cytokine-mediated inflammatory responses. An alteration of VD metabolism in terms of increased 24-hydroxylase mRNA and protein expression has been demonstrated in endometrial cancer, albeit not consistently. The effect of the active form of the vitamin as an anti-proliferative, pro-apoptotic, anti-inflammatory, and differentiation-inducing agent has been demonstrated in various endometrial cancer cell lines.
Topics: Endometriosis; Endometrium; Female; Fertility; Humans; Menstrual Cycle; Myometrium; Receptors, Calcitriol; Signal Transduction; Vitamin D
PubMed: 30096760
DOI: 10.3390/ijms19082320 -
BJOG : An International Journal of... Aug 2018Caesarean section (CS) rates are rising globally. Long-term adverse outcomes after CS might be reduced when the optimal uterine closure technique becomes evident. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Caesarean section (CS) rates are rising globally. Long-term adverse outcomes after CS might be reduced when the optimal uterine closure technique becomes evident.
OBJECTIVE
To determine the effect of uterine closure techniques after CS on maternal and ultrasound outcomes.
SEARCH STRATEGY
Literature search in electronic databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or prospective cohort studies that evaluated uterine closure techniques and reported on ultrasound findings, perioperative or long-term outcomes.
DATA COLLECTION AND ANALYSIS
Twenty studies (15 053 women) were included in our meta-analyses for various outcomes. We calculated pooled risk ratios (RR) and weighted mean differences (WMD) with 95% CI through random-effect analysis.
MAIN RESULTS
Residual myometrium thickness (RMT), reported in eight studies (508 women), decreased by 1.26 mm after single- compared with double-layer closure (95% CI -1.93 to -0.58), particularly when locked sutures were used. Healing ratio [RMT/adjacent myometrium thickness (AMT)] decreased after single-layer closure (WMD -7.74%, 95% CI -13.31 to -2.17), particularly in the case of locked sutures. Niche prevalence increased (RR 1.71, 95% CI 1.11-2.62) when the decidua was excluded. Dysmenorrhea occurred more often in the single-layer group (RR 1.23, 95% CI 1.01-1.48), whereas incidence of uterine rupture was similar (RR 1.91, 95% CI 0.63-5.74).
CONCLUSION
Double-layer unlocked sutures are preferable to single-layer locked sutures regarding RMT, healing ratio and dysmenorrhoea. Excluding the decidua seems to result in higher niche prevalence. As thin residual myometrium or niches may serve as intermediates for gynaecological and reproductive outcomes, future studies should focus on these outcomes. TWEETABLE ABSTRACT: #Uterineclosuretechniques after #caesarean affect #longtermoutcomes.
Topics: Abdominal Wound Closure Techniques; Cesarean Section; Dysmenorrhea; Female; Humans; Myometrium; Postoperative Complications; Pregnancy; Prospective Studies; Randomized Controlled Trials as Topic; Suture Techniques; Treatment Outcome; Ultrasonography; Uterine Rupture; Uterus; Wound Healing
PubMed: 29215795
DOI: 10.1111/1471-0528.15048 -
The Cochrane Database of Systematic... Nov 2017Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive.Fibroid growth is stimulated by oestrogen. Gonadotropin-hormone releasing analogues (GnRHa) induce a state of hypo-oestrogenism that shrinks fibroids , but has unacceptable side effects if used long-term. Other potential hormonal treatments, include progestins and selective progesterone-receptor modulators (SPRMs).This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments.
OBJECTIVES
To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials.
SELECTION CRITERIA
We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low-quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD -175 mL, 95% CI -219.0 to -131.7; 13 studies; 858 participants; I² = 67%; low-quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate-quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate-quality evidence).Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (-9.59 minutes, 95% CI 15.9 to -3.28; 6 studies; 617 participants; I² = 57%; low-quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate-quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low-quality evidence).GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low-quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low-quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (-47% with GnRHa compared to -20% and -22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low-quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate-quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate-quality evidence) or haemoglobin levels (MD -0.2, 95% CI -0.6 to 0.2; 188 participants; moderate-quality evidence).There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI -5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low-quality evidence).The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB-2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high-quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low-quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low-quality evidence; asoprisnil: MD -166.9 mL; 95% CI -277.6 to -56.2; 1 study; 22 participants; low-quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured.
AUTHORS' CONCLUSIONS
A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid-related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost-effectiveness and distinguish between groups of women with fibroids who would most benefit.
Topics: Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Chemotherapy, Adjuvant; Dopamine Agonists; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Myometrium; Operative Time; Preoperative Care; Progestins; Randomized Controlled Trials as Topic; Uterine Neoplasms
PubMed: 29139105
DOI: 10.1002/14651858.CD000547.pub2 -
American Journal of Reproductive... Feb 2018Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory... (Review)
Review
Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1β, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.
Topics: Animals; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Cyclooxygenase 2; Female; Humans; Inflammation; Inflammation Mediators; Metalloporphyrins; Parturition; Pregnancy; Uterus
PubMed: 29076197
DOI: 10.1111/aji.12776 -
Journal of Gynecologic Oncology Nov 2017To compare the diagnostic accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration (MI) in endometrial... (Comparative Study)
Comparative Study Meta-Analysis Review
Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with endometrial cancer: a systematic review and meta-analysis.
OBJECTIVE
To compare the diagnostic accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration (MI) in endometrial carcinoma.
METHODS
An extensive search of papers comparing TVS and MRI in assessing MI in endometrial cancer was performed in MEDLINE (PubMed), Web of Science, and Cochrane Database from January 1989 to January 2017. Quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
RESULTS
Our extended search identified 747 citations but after exclusions we finally included in the meta-analysis 8 articles. The risk of bias for most studies was low for most 4 domains assessed in QUADAS-2. Overall, pooled estimated sensitivity and specificity for diagnosing deep MI were 75% (95% confidence interval [CI]=67%-82%) and 82% (95% CI=75%-93%) for TVS, and 83% (95% CI=76%-89%) and 82% (95% CI=72%-89%) for MRI, respectively. No statistical differences were found when comparing both methods (p=0.314). Heterogeneity was low for sensitivity and high for specificity for TVS and MRI.
CONCLUSION
MRI showed a better sensitivity than TVS for detecting deep MI in women with endometrial cancer. However, the difference observed was not statistically significant.
Topics: Endometrial Neoplasms; Female; Humans; Magnetic Resonance Imaging; Myometrium; Neoplasm Invasiveness; Preoperative Care; Sensitivity and Specificity; Ultrasonography; Vagina
PubMed: 29027404
DOI: 10.3802/jgo.2017.28.e86