RESUMEN
Fibroids are benign uterine tumors characterized by the proliferation of uterine smooth muscle cells, embedded in an abundant extracellular matrix. Their prevalence is estimated to be >50% in women aged >45 years. Fibroids represent a considerable health burden. It is time to acquire a deeper mechanistic understanding of uterine fibroid-related etiology and pathogenesis, which may help pinpoint new strategies and an individualized approach. There is a need to gather prospective data and conduct studies to compare alternative approaches and assess long-term outcomes with respect to quality of life, recurrence of symptoms (bleeding and bulk symptoms), fertility, and even complications The goal of this review was to evaluate the widely accepted pathogenesis and identify risks factors and future directions for clinical and basic research into fibroids.
Asunto(s)
Leiomioma , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/patología , Leiomioma/epidemiología , Neoplasias Uterinas/patología , Neoplasias Uterinas/epidemiología , Neoplasias Uterinas/etiología , Factores de Riesgo , AnimalesRESUMEN
BACKGROUND: Outdoor air pollution is a ubiquitous exposure that includes endocrine-disrupting and carcinogenic compounds that may contribute to the risk of hormone-sensitive outcomes such as uterine cancer. However, there is limited evidence about the relationship between outdoor air pollution and uterine cancer incidence. METHODS: We investigated the associations of residential exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2) with uterine cancer among 33â417 Sister Study participants with an intact uterus at baseline (2003-2009). Annual average air pollutant concentrations were estimated at participants' geocoded primary residential addresses using validated spatiotemporal models. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association between time-varying 12-month PM2.5 (µg/m3) and NO2 (parts per billion; ppb) averages and uterine cancer incidence. RESULTS: Over a median follow-up period of 9.8 years, 319 incident uterine cancer cases were identified. A 5-ppb increase in NO2 was associated with a 23% higher incidence of uterine cancer (hazard ratio = 1.23, 95% confidence interval = 1.04 to 1.46), especially among participants living in urban areas (hazard ratio = 1.53, 95% confidence interval = 1.13 to 2.07), but PM2.5 was not associated with increased uterine cancer incidence. CONCLUSION: In this large US cohort, NO2, a marker of vehicular traffic exposure, was associated with a higher incidence of uterine cancer. These findings expand the scope of health effects associated with air pollution, supporting the need for policy and other interventions designed to reduce air pollutant exposure.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Exposición a Riesgos Ambientales , Dióxido de Nitrógeno , Material Particulado , Neoplasias Uterinas , Humanos , Femenino , Persona de Mediana Edad , Incidencia , Neoplasias Uterinas/epidemiología , Neoplasias Uterinas/etiología , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Anciano , Modelos de Riesgos Proporcionales , Adulto , Estados Unidos/epidemiologíaRESUMEN
Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs for the health care system and the substantial impact on women's quality of life, they are a significant public health concern. Previous literature on the impact of diet on the occurrence, growth and symptoms of fibroids is limited. Recently, many papers have been written on this topic. A scoping review of PubMed and Cochrane databases was performed using the following keywords: uterine fibroids, antioxidants, diet, diet, vegetarian, vegetables, fruits, meat and soy foods, dairy products, tea, vitamin D, vitamin C, ascorbic acid. Preliminary research has shown a beneficial effect of vegetable and fruit consumption on the occurrence of fibroids. A relationship between hypovitaminosis D and an increased risk of fibroids has also been demonstrated. Studies on epigallocatechin gallate showed its apoptosis-promoting and antifibrinolytic effect in fibroid cells. Initial results are promising, but further randomized trials are needed to draw firm conclusions about the effects of diet and nutrients on uterine fibroids.
Asunto(s)
Leiomioma , Neoplasias Uterinas , Femenino , Humanos , Neoplasias Uterinas/etiología , Neoplasias Uterinas/patología , Calidad de Vida , Leiomioma/epidemiología , Vitaminas , Dieta/efectos adversos , Verduras , Ácido AscórbicoRESUMEN
PURPOSE: To study whether it is better to perform or not a myomectomy, in terms of surgical and reproductive outcomes in patients of advanced reproductive age, by an observational prospective study in university-affiliated and Community Hospitals. MATERIALS AND METHODS: 40 years and older patients affected by non-submucous symptomatic uterine fibroids and desiring future fertility were enrolled and treated by laparoscopic intracapsular myomectomy by (LIM) or by open laparotomy (OIM), or by a non-surgical management as control group, while attempting to conceive. The primary outcome measures were fibroid characteristics, pre- and post-surgical parameters, pregnancy achievement; the secondary outcome measures were the spontaneous or ART pregnancy outcomes, eventual week of abortion and type of delivery. Propensity scores have been calculated with logistic regression for binary and continuous variables. RESULTS: 202 patients completed the study: 112 operated by LIM, 40 by OIM and 50 patients as control group. Patients undergoing OIM have a worse surgical outcome than LIM. No difference was seen in pregnancy either after myomectomy or control group during follow-up. In the LIM group, there were 44 pregnancies (39.2%), and in the OIM group, there were 9 (22.5%) and 16 in the control group (32%). The weeks of delivery were statistically greater for the control group versus the surgical groups, with no difference in Apgar score between the 3 groups. CONCLUSION: Patients aged over 40 years did not show substantial differences in reproductive outcome, whether operated or not. Myomectomy in over 40-year-old patients has no detrimental effect on future pregnancy rates and over when compared to expectant management.
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Laparoscopía , Miomectomía Uterina , Neoplasias Uterinas , Embarazo , Humanos , Adulto , Femenino , Persona de Mediana Edad , Miomectomía Uterina/efectos adversos , Índice de Embarazo , Neoplasias Uterinas/etiología , Estudios Prospectivos , Puntaje de Propensión , Laparoscopía/efectos adversosRESUMEN
OBJECTIVE: To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia. METHODS: The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed. RESULTS: A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD. CONCLUSION: The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy.
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Hiperplasia Endometrial , Dispositivos Intrauterinos Medicados , Dispositivos Intrauterinos , Neoplasias Uterinas , Tromboembolia Venosa , Embarazo , Femenino , Humanos , Progestinas/uso terapéutico , Levonorgestrel/uso terapéutico , Tromboembolia Venosa/etiología , Hiperplasia Endometrial/etiología , Neoplasias Uterinas/etiología , Dispositivos Intrauterinos Medicados/efectos adversosRESUMEN
BACKGROUND: Pituitrin injection solution is an indispensable hemostatic utilized in clinical practice and is widely used in myomectomy. However, there have been reports of adverse reactions leading to gastrointestinal injury, hyponatremia and hypokalemia, anaphylaxis, cardiac arrest, etc. Thus, the safety of pituitrin should be taken seriously. CASE PRESENTATION: In the present study, three cases of cardiac arrest caused by pituitrin injection during laparoscopic myomectomy, who were successfully resuscitated in our hospital, are reported. CONCLUSION: The clinical data and surgical procedures in the patient should be analyzed to find the causes of cardiac arrest. Medication and resuscitation should be summarized to ensure the safety of the patient.
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Paro Cardíaco , Laparoscopía , Hormonas Neurohipofisarias , Miomectomía Uterina , Neoplasias Uterinas , Femenino , Humanos , Miomectomía Uterina/efectos adversos , Miomectomía Uterina/métodos , Paro Cardíaco/inducido químicamente , Inyecciones , Laparoscopía/efectos adversos , Laparoscopía/métodos , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/etiologíaRESUMEN
PURPOSE: Uterine myomas are the most common gynecological disease. In these cases, a myomectomy is performed traditionally laparotomically. However, alternatives have been widely used, including laparoscopic, endoscopic, and robotic surgery. During these techniques, diffuse parenchymatous bleeding remains one of the main intraoperative and postoperative complications and sometimes requires unplanned hysterectomies. Recently, hemostatic agents and sealants have been used to prevent excessive blood loss during surgical repair. METHODS: We propose a prospective case-control study on the use of a sealing hemostat patch (HEMOPATCH®) on uterine sutures in laparotomic myomectomy. In the period between July 2016 and April 2017, 46 patients with symptomatic uterine fibromatosis underwent surgery. They were divided into two groups of 23 patients, with different treatments in the hemostatic phase of oozing bleeding. HEMOPATCH® is applied in group A, and spray electrocoagulation is applied in group B. RESULTS: In group A, we achieve faster hemostasis (p < 0.05), than in group B. We report a significantly lower C-reactive protein value on the second and third days after surgery for group A compared to group B. CONCLUSIONS: HEMOPATCH®, during laparotomic myomectomy, is a valid alternative solution for obtaining rapid hemostasis and consequently intraoperative and postoperative bleeding. Furthermore, we suggest that a lower inflammatory peritoneal state is probably correlated with the barrier effect of the patch on the suture.
Asunto(s)
Hemostáticos , Laparoscopía , Leiomioma , Miomectomía Uterina , Neoplasias Uterinas , Femenino , Humanos , Miomectomía Uterina/métodos , Pérdida de Sangre Quirúrgica/prevención & control , Estudios de Casos y Controles , Leiomioma/cirugía , Leiomioma/etiología , Hemostáticos/uso terapéutico , Laparoscopía/métodos , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/etiologíaRESUMEN
OBJECTIVE: To assess comparative rates of further uterine-preserving procedures (UPP) or hysterectomy reintervention, after myomectomy or uterine artery embolisation (UAE). DESIGN: Population-based, retrospective cohort study. SETTING: England. POPULATION: Women who underwent myomectomy or UAE between 2010 and 2015 under the NHS. METHODS: Data was abstracted from NHS Health Episode Statistics datasets. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional-hazards regression. MAIN OUTCOMES MEASURES: 30-day readmission, UPP and hysterectomy reintervention rates. RESULTS: 9443 and 6224 women underwent elective myomectomy or UAE, respectively. After 118 136 total person-years of follow-up, the rate of hysterectomy was 8.34 and 20.98 per 1000 patient years for myomectomy or UAE, respectively. There was a 2.4-fold increased risk of undergoing hysterectomy after UAE when compared with myomectomy in adjusted models (HR 2.38 [95% CI 2.10-2.66]) [adjusted for age, ethnicity, multiple deprivation index, geographical region and comorbidities]. The HR for undergoing a UPP reintervention was 1.44 (95% CI 1.29-1.60) in favour of myomectomy. The rate of hysterectomy was increased 22% following UAE compared with laparoscopic myomectomy (0.97-1.52). Age may influence reintervention rates, and there was variation in hysterectomy risk when stratified by geographical region. CONCLUSIONS: After a median of 7 years of follow-up, there is a 2.4-fold increased rate of hysterectomy and 44% increased risk of UPPs as reintervention after UAE, relative to myomectomy. These findings will aid pre-procedure counselling for women with fibroids. Future work should investigate the effect of other outcome modifiers, such as fertility intentions and fibroid anatomical characteristics.
Asunto(s)
Leiomioma , Embolización de la Arteria Uterina , Miomectomía Uterina , Neoplasias Uterinas , Femenino , Humanos , Miomectomía Uterina/efectos adversos , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/etiología , Estudios Retrospectivos , Histerectomía , Leiomioma/cirugía , Leiomioma/etiología , Resultado del TratamientoRESUMEN
OBJECTIVES: This study intended to compare the safety and clinical efficacy between two treatments of uterine fibroids: laparoscopic myomectomy (LM) and high intensity focused ultrasound (HIFU). MATERIAL AND METHODS: Clinical data were collected from 587 uterine fibroid patients who were treated in The People's Hospital of Nanchuan, Chongqing from January 1, 2018 to December 31, 2019. Among the patients, 287 cases were treated with HIFU (observation group), and 300 cases were treated with LM (control group). The progression-free survival (PFS) was taken as the primary endpoint. The secondary endpoints included operation results (including operative time, intraoperative blood loss, and intraoperative fluid replacement), complications, hemoglobin level one month after surgery and clinical efficacy. In addition, the fibroid volume of the observation group before treatment and 3, 6, and 12 months after treatment were also analyzed. RESULTS: The operative time of observation group was evidently shortened compared to the control group, and the intraoperative blood loss and intraoperative fluid replacement of observation group were also considerably reduced (all p < 0.05), but there was no significant difference in the hemoglobin level between the two groups one month after surgery (p > 0.05). In terms of curative effect, the total effective rate of HIFU group and LM group was 98.6% (283/287) and 95.3% (286/300) respectively, with statistically significant difference (p < 0.05). In terms of complications, the incidence of bleeding and infection in HIFU group was obviously lower than that in LM group (both p < 0.05), while no significant differences were observed in the remaining complications (all p > 0.05). Fibroid volume comparisons before treatment and 3, 6 and 12 months after operation in observation group showed that fibroid volume decreased significantly (all p < 0.05). The median follow-up time was 30.6 months. The mean PFS of patients in the observation group and control group was 29.71 months (95% CI 28.24-29.75) and 26.74 months (95% CI 26.49-28.33), respectively (HR 0.47; 95% CI, 0.29 to 0.76; Log-rank p = 0.0019). CONCLUSIONS: HIFU could improve the intraoperative efficacy and reduce the complications of patients with uterine fibroids and has excellent performance in improving clinical efficacy and prolonging PFS. HIFU can be used as an alternative to surgical treatment.
Asunto(s)
Leiomioma , Miomectomía Uterina , Neoplasias Uterinas , Femenino , Humanos , Miomectomía Uterina/efectos adversos , Miomectomía Uterina/métodos , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/etiología , Pérdida de Sangre Quirúrgica , Leiomioma/diagnóstico por imagen , Leiomioma/cirugía , Resultado del Tratamiento , HemoglobinasRESUMEN
OBJECTIVE: Mode of delivery has long-term implications on the mother, including recent data regarding the level of transmission of fetal microchimeric cells (FMc) and their possible effect on cancer development. We aimed to evaluate the association between cesarean section (CS) and future risk for neoplasms. STUDY DESIGN: A population-based cohort analysis comparing the long-term risk for neoplasms between patients that delivered only by CS to those that delivered only vaginally (VD). Neoplasms were pre-defined based on ICD-9 codes. Deliveries occurred between the years 1991-2017 in a tertiary medical center. Kaplan-Meier survival curves were used to compare the cumulative incidence of neoplasms and Cox proportional hazards models were constructed to control for confounders. RESULTS: During the study period 105,992 patients met the inclusion criteria; 14150 (13.4%) of patients had only CS and 91842 (86.6%) had VD (comparison group). The CS group had significantly higher incidence of benign and malignant neoplasms (4.73 per 1000 patient-years versus 3.88 per 1000 patient-years, OR = 1.26, 95% CI 1.16-1.37; p = 0.001; 2.19 per 1000 patient-years of follow up versus 1.93 per 1000 patient-years, OR = 1.16, 95% CI 1.03-1.31; p = 0.013). Specifically, the CS group had higher incidence of uterine cancer (1.2 versus 0.06 per 1000 patient-years, OR = 1.97, 95% CI 1.14-3.39; p = 0.013). The cumulative incidence of benign, malignant and uterine neoplasms was significantly higher in the CS group (Log rank test p = 0.001; 0.036 and 0.014; respectively). Importantly, no significant association was found with breast and ovarian malignancies." When performing a Cox regression model controlling for confounders, the risk for malignancy-related hospitalizations remained significant (adjusted HR = 1.22, 95% CI 1.01-1.48; p = 0.031) but not for uterine cancer (adjusted HR = 1.6, 95% CI 0.9-2.8; p = 0.103). CONCLUSION: Our findings provide support to linkage between delivery by cesarean section and future maternal malignancy.
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Neoplasias Ováricas , Neoplasias Uterinas , Humanos , Embarazo , Femenino , Cesárea/efectos adversos , Estudios de Cohortes , Factores de Riesgo , Neoplasias Ováricas/etiología , Hospitalización , Modelos de Riesgos Proporcionales , Neoplasias Uterinas/etiología , Estudios RetrospectivosRESUMEN
According to recent studies and observations in clinical practice, uterine fibroids increase the risk of preterm birth. There are several theories on the pathogenesis of preterm birth in the presence of fibroids. One theory proclaims that fibroid necrosis leads to preterm birth, though pathophysiological mechanisms have not been described. Necrotic tissue secretes specific cytokines and proteins and we suggest these to be comparable to the inflammatory response leading to spontaneous preterm birth. We hypothesize that fibroid necrosis could induce preterm parturition through a similar inflammatory response. This new hypothesis generates novel perspectives for future research and the development of preventative strategies for preterm birth. Moreover, we emphasize the importance of the recognition of fibroids and especially fibroid necrosis by clinicians during pregnancy.
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Leiomioma , Nacimiento Prematuro , Neoplasias Uterinas , Femenino , Humanos , Recién Nacido , Inflamación/complicaciones , Leiomioma/etiología , Necrosis , Embarazo , Nacimiento Prematuro/etiología , Neoplasias Uterinas/etiología , Neoplasias Uterinas/patologíaRESUMEN
OBJECTIVES: The goal of this study was to examine the safety, feasibility, and effectiveness of the use of a microsurgical temporary vascular clip system to facilitate the laparoscopic enucleation of very large intramural uterine fibroids. METHODS: In this retrospective study, the surgical outcomes of 26 patients who underwent laparoscopic myomectomy with temporary uterine vessel clipping for very large (the largest measured diameter ≥ 9 cm) symptomatic intramural uterine fibroids in two tertiary referral hospitals between September 2017 and March 2020 were examined. Titan-made vascular clips (YASARGIL® Aneurysm Clip System) were used to temporarily occlude the bilateral uterine arteries and utero-ovarian vessels. Main outcomes included operating time, blood loss, number of leiomyomas and weight, conversion rate, intra- and postoperative complication rates, and length of hospital stay. RESULTS: Twenty six patients were included. Dominant intramural uterine fibroid diameters were 9-22 cm. The general characteristics of the patients were similar. The mean surgery duration and intraoperative blood loss were 175.3 ± 32.7 (range 120-250) min and 241.1 ± 103 (range 100-450) ml, respectively. The median postoperative drop in hemoglobin was 0.89 ± 0.75 g/dL. No patient required blood transfusion. No procedure was converted to laparotomy. No major intra- or postoperative complication occurred. CONCLUSIONS: Laparoscopic myomectomy for very large intramural uterine fibroids can be performed safely and effectively, with less intraoperative blood loss, using vascular clips for temporary clamping of the bilateral uterine vessels.
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Laparoscopía , Leiomioma , Miomectomía Uterina , Neoplasias Uterinas , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Laparoscopía/métodos , Leiomioma/etiología , Leiomioma/cirugía , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Instrumentos Quirúrgicos , Miomectomía Uterina/métodos , Neoplasias Uterinas/etiología , Neoplasias Uterinas/cirugíaRESUMEN
STUDY OBJECTIVE: To assess rates of and factors associated with complications and reoperation after myomectomy. DESIGN: Population-based cohort study. SETTING: All non-Veterans Affairs facilities in the state of California from January 1, 2005, to December 31, 2018. PARTICIPANTS: Women undergoing abdominal or laparoscopic myomectomy for myoma disease were identified from the Office of Statewide Health Planning and Development datasets using appropriate International Classification of Diseases, Ninth and Tenth Revision and Current Procedural Terminology codes. INTERVENTIONS: Demographics, surgery facility type, facility surgical volume, and surgical approach were identified. Primary outcomes included complications occurring within 60 days of surgery and reoperations for myomas. Patients were followed up for over an average of 7.3 years. Univariate and multivariable associations were explored between the above factors and rates of complications and reoperation. All odds ratios (ORs) are adjusted ORs. MEASUREMENTS AND MAIN RESULTS: Of the 66 012 patients undergoing myomectomy, 5265 had at least one complication (8.0%). Advanced age, black, Asian race, MediCal and Medicare payor status, academic facility, and medical comorbidities were associated with increased odds of a complication. Minimally invasive myomectomy (MIM) was associated with decreased complications compared with abdominal myomectomy (AM) (OR, 0.29; 95% confidence interval [CI], 0.25-0.33; p <.001). Overall, 17 377 patients (26.3%) underwent reoperation. Medicare and MediCal payor status and medical comorbidities were associated with increased odds of a repeat surgery. Reoperation rates were higher in the MIM group over the entire study period (OR, 2.33; 95% CI, 1.95-2.79; p <.001). However, the odds of reoperation after MIM decreased each year (OR, 0.93; 95% CI 0.92-0.95; p <.001), with the odds of reoperation after AM surpassing MIM in 2015. CONCLUSION: This study identifies outcome disparities in the surgical management of myomas and describes important differences in the rates of complications and reoperations, which can be used to counsel patients on surgical approach. These findings suggest that MIM can be considered a lasting and safe approach in properly selected patients.
Asunto(s)
Laparoscopía , Leiomioma , Mioma , Miomectomía Uterina , Neoplasias Uterinas , Anciano , Femenino , Humanos , Estudios de Cohortes , Electrólitos , Laparoscopía/efectos adversos , Leiomioma/etiología , Leiomioma/cirugía , Medicare , Mioma/cirugía , Reoperación , Estudios Retrospectivos , Estados Unidos , Miomectomía Uterina/efectos adversos , Neoplasias Uterinas/etiología , Neoplasias Uterinas/cirugíaRESUMEN
STUDY OBJECTIVE: To analyze the frequency and risk factors of postsurgical intrauterine adhesions (IUAs) using second-look hysteroscopy (SLH) in patients undergoing hysteroscopic myomectomy performed using the myoma pseudocapsule preservation technique for submucosal myoma. DESIGN: Retrospective cohort study. SETTING: University hospital from January 2017 to December 2019. PATIENTS: A total of 124 patients underwent hysteroscopic myomectomy and SLH. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Surgical duration, intraoperative blood loss, number of enucleated myomas, volume of specimen, and postsurgical IUA evaluated by SLH. Postsurgical IUA were found in 5 of 124 cases (4.0%) at SLH. There were no cases of IUA formation in cases in which a single myomas was resected (0 of 83 cases, 0%); all cases were multiple myomas (5 of 41 cases, 12.2%), and IUA significantly occurred more frequently in cases of multiple myoma (p = .003). Univariate analyses showed that the IUA group contained a significantly larger number of enucleated uterine myoma (p <.001), required a longer operation (p = .003), and displayed an increased volume of intraoperative bleeding (p = .007), and the heavier the specimen, the greater the number of patients that had inserted an intrauterine device than the group that did not display postsurgical IUA. Multivariate logistic regression analysis of the risk factors of postsurgical IUA showed that the number of enucleated myomas was strongly associated with IUA (odds ratio, 1.45; 95% confidence interval, 1.06-1.97). CONCLUSION: The frequency of postsurgical IUA after hysteroscopic myomectomy was high in cases of multiple myoma and may be a risk factor. SLH should be actively pursued in cases where the patient desires to bear children, and an informed consent should be attained before performing surgery.
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Mioma , Enfermedades Uterinas , Miomectomía Uterina , Neoplasias Uterinas , Femenino , Humanos , Histeroscopía/efectos adversos , Histeroscopía/métodos , Embarazo , Estudios Retrospectivos , Adherencias Tisulares/etiología , Enfermedades Uterinas/etiología , Miomectomía Uterina/efectos adversos , Miomectomía Uterina/métodos , Neoplasias Uterinas/etiología , Neoplasias Uterinas/cirugíaRESUMEN
Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids. This paper comprehensively summarizes the recent research advances on uterine fibroids, focusing on risk factors, development origin, pathogenetic mechanisms, and treatment options. Additionally, we describe the current treatment interventions for uterine fibroids. Finally, future perspectives on uterine fibroids studies are summarized. Deeper mechanistic insights into tumor etiology and the complexity of uterine fibroids can contribute to the progress of newer targeted therapies.
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Leiomioma , Neoplasias Uterinas , Femenino , Humanos , Leiomioma/etiología , Leiomioma/terapia , Miometrio/patología , Factores de Riesgo , Neoplasias Uterinas/etiología , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapiaRESUMEN
Uterine leiomyosarcoma (ULMS) is a malignancy, which arises from the uterine smooth muscle. Because of its rarity, aggressive nature, and extremely poor prognosis, the molecular mechanisms driving ULMS remain elusive. To identify candidate cancer genes (CCG) driving ULMS, we conducted an in vivo Sleeping Beauty (SB) transposon mutagenesis screen in uterine myometrium-specific, PTEN knockout, KRAS mutant (PTEN KO/KRAS) mice. ULMS quickly developed in SB PTEN KO/KRAS mice, but not in PTEN KO/KRAS mice, demonstrating the critical importance of SB mutagenesis for driving ULMS in this model. Subsequent sequencing of SB insertion sites in these tumors identified 19 ULMS CCGs that were significantly enriched in known cancer genes. Among them, Zfp217 and Sfmbt2 functioned at early stages of tumor initiation and appeared to be oncogenes. Expression of ZNF217, the human homolog of ZFP217, was shown to be elevated in human ULMS compared with paired normal uterine smooth muscle, where it negatively correlated with patient prognosis. Inhibition of ZNF217 suppressed, whereas overexpression induced, proliferation, survival, migration, and stemness of human ULMS. In a second ex vivo ULMS SB metastasis screen, three CCGs were identified that may drive ULMS metastasis to the lung. One of these CCGs, Nrd1 (NRDC in humans), showed stronger expression in human metastatic tumors compared with primary ULMS and negatively associated with patient survival. NRDC knockdown impaired migration and adhesion without affecting cell proliferation, whereas overexpression had the opposite effect. Together, these results reveal novel mechanism driving ULMS tumorigenesis and metastasis and identify ZNF217 and NRDC as potential targets for ULMS therapy. SIGNIFICANCE: An in vivo Sleeping Beauty transposon mutagenesis screen identifies candidate cancer genes that drive initiation and progression of uterine leiomyosarcoma and may serve as therapeutic targets.
Asunto(s)
Biomarcadores de Tumor/genética , Elementos Transponibles de ADN , Leiomiosarcoma/patología , Neoplasias Pulmonares/secundario , Mutagénesis Insercional , Mutación , Neoplasias Uterinas/patología , Animales , Femenino , Humanos , Leiomiosarcoma/etiología , Leiomiosarcoma/metabolismo , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fosfohidrolasa PTEN/fisiología , Proteínas Proto-Oncogénicas p21(ras)/fisiología , Transposasas/genética , Transposasas/metabolismo , Neoplasias Uterinas/etiología , Neoplasias Uterinas/metabolismoRESUMEN
Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found.
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Aberraciones Cromosómicas , Reparación del ADN , Leiomioma/genética , Complejo Mediador/genética , Paridad , Neoplasias Uterinas/genética , Adulto , Fenómenos Biomecánicos , Roturas del ADN de Doble Cadena , Femenino , Expresión Génica , Humanos , Histerectomía , Cariotipo , Leiomioma/etiología , Leiomioma/patología , Leiomioma/cirugía , Mutación , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Miometrio/metabolismo , Miometrio/patología , Embarazo , Cultivo Primario de Células , Estudios Prospectivos , Neoplasias Uterinas/etiología , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugíaRESUMEN
Uterine leiomyomas represent the most common benign gynecologic tumor. These hormone-dependent smooth-muscle formations occur with an estimated prevalence of ~70% among women of reproductive age and cause symptoms including pain, abnormal uterine bleeding, infertility, and recurrent abortion. Despite the prevalence and public health impact of uterine leiomyomas, available treatments remain limited. Among the potential causes of leiomyomas, early hormonal exposure during periods of development may result in developmental reprogramming via epigenetic changes that persist in adulthood, leading to disease onset or progression. Recent developments in unbiased high-throughput sequencing technology enable powerful approaches to detect driver mutations, yielding new insights into the genomic instability of leiomyomas. Current data also suggest that each leiomyoma originates from the clonal expansion of a single transformed somatic stem cell of the myometrium. In this review, we propose an integrated cellular and molecular view of the origins of leiomyomas, as well as paradigm-shifting studies that will lead to better understanding and the future development of non-surgical treatments for these highly frequent tumors.
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Leiomioma/patología , Neoplasias Uterinas/patología , Útero/patología , Animales , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Leiomioma/etiología , Leiomioma/genética , Mutación , Neoplasias Uterinas/etiología , Neoplasias Uterinas/genética , Útero/metabolismoRESUMEN
Many women apply powder to the genital area as a drying agent. Talc, an inert mineral with a high capacity to absorb water, has historically been a major component of body powders. Due to its similarity and co-occurrence with asbestos, the association of body powder/talc use and gynecological cancer risk, specifically ovarian cancer risk, has been a long-standing research question. Retrospective case-control studies have shown associations between genital powder use and ovarian cancer risk, with summary relative risk estimates from meta-analyses and pooled analyses ranging from 1.24 to 1.35 for ever versus never use. In contrast, prospective cohort studies have not shown a statistically significant association until recently, when a pooled analysis of four large cohorts demonstrated a weak, but statistically significant association among women with patent reproductive tracts (hazard ratio 1.13). Taken together, the epidemiological data from case-control studies and cohort studies suggest that there may be a small, positive association between genital powder use and ovarian cancer. The causal factors underlying this association are not clear. Proposed factors include talc, other minerals, such as asbestos or quartz, that are known carcinogens and may contaminate talc products, or other powder ingredients that could cause inflammation of the reproductive tracts. Given the rarity of ovarian cancer in the general population, the small increase in relative risk translates to a very low increase in absolute risk. Further research is needed to understand the underpinnings of the observed association between genital powder use and ovarian cancer risk.
Asunto(s)
Neoplasias Ováricas/etiología , Talco/efectos adversos , Femenino , Humanos , Histerectomía/efectos adversos , Neoplasias Ováricas/epidemiología , Polvos , Riesgo , Esterilización Tubaria/efectos adversos , Factores de Tiempo , Neoplasias Uterinas/etiologíaRESUMEN
INTRODUCTION: Gestational trophoblastic neoplasia (GTN) include a group of malignant neoplasms that originate from the trophoblasts of placental tissue in molar or nonmolar pregnancy. Currently, it is unclear whether the prognosis of high-risk GTN or gestational choriocarcinoma succeeding molar pregnancy or that following a nonmolar one is better. Comparison of the genetic short tandem repeat (STR) patterns of the DNA extracted from the tumor, patient, and her partner allows the genetic origins of the choriocarcinoma to be distinguished - whether it is gestational or non-gestational and whether it is derived from a molar or nonmolar pregnancy in the event it is gestational. This study aimed to investigate the causative pregnancy of patients with high-risk GTN, especially those with poor outcomes, and assess the impact of the causative pregnancy on patient outcome. METHODS: We evaluated 24 patients who were diagnosed with high-risk GTN between January 2000 and October 2019, including 15 cases of pathologically proven gestational choriocarcinomas and the causative pregnancy was investigated by STR analysis in which tumor DNA could be extracted. RESULTS: In high-risk GTN without history of anteceding molar pregnancies, nonmolar pregnancy was the causative pregnancy, which was confirmed in three cases. Molar pregnancy appeared be the causative pregnancy of high-risk GTN in patients with a history of antecedent molar pregnancies either with or without interruption by subsequent nonmolar pregnancies prior to developing high-risk GTN. High-risk GTN in most of the evaluated deceased cases (three of four) was due to nonmolar pregnancy, while all but one case with molar pregnancy as the causative pregnancy survived. DISCUSSION: STR analysis can distinguish the causative pregnancy of high-risk GTN, and nonmolar pregnancy as the causative pregnancy might have negative effects on the outcome of the disease.