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Minimally invasive techniques for myomectomy are based on the rationale of preserving the myometrial integrity, in order to spare muscular and fibro-neurovascular myometrial fibers and ensure complete and bloodless myoma removal. Post-operative myometrial vascularization is crucial in injured muscle regeneration. The post-surgical myometrial healing is needful for uterine reproductive function. Neurotransmitters and neurofibers were analyzed in the myoma pseudocapsule surrounding fibroid. They activate signaling molecule synthesis and release which, in turn, promote cell activation and induce muscle regeneration and growth. Pseudocapsule damage during myomectomy may lead to a reduction of neuropeptides and neurofibers at the hysterotomic site, to a poor physiological myometrial healing, with more fibrosis due to hypoxia, ischemia and necrosis. These pathophysiological events cause deficit in myometrial neurotransmission, muscular impulse and contractility, with ultimately impaired uterine muscle function during pregnancy, labor and delivery. Hence, during myomectomy, all manipulations should be performed as precisely and bloodlessly as possible, avoiding extensive, high wattage diathermocoagulation or excessive tissue manipulation or muscular trauma. Any iatrogenic pseudocapsule damage may alter neurotransmitter function during successive myometrial healing, impacting negatively on uterine repair and on eventual pregnancies. Hence the reasoned myomectomy on a biological basis, the "intracapsular myomectomy", satisfied these surgical and physiological requirements. It was described precisely and firstly by the hysteroscopy, with the image magnification of the preservation of the myoma pseudocapsule. The "intracapsular hysteroscopic myomectomy" demonstrated the safe and effective removal of submucous myomas with intramural development. It allowed to completely remove the myoma in one or two surgical steps, saving the pseudocapsule and the surrounding healthy myometrium. The respect of the myometrium and the reduced thermal injury, a part the excellent outcomes in terms of surgical complications prevention, post-surgical fibrosis and intrauterine synechiae reduction, highlighted the physiological development of a successive pregnancy, without any myometrial complications during pregnancy, labor and delivery., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: To test whether variations in apparent diffusion coefficient (ADC) values of uterine leiomyomas after uterine artery embolization (UAE) may correlate with outcome and assess the effects of UAE on leiomyomas and normal myometrium with magnetic resonance imaging (MRI)., Methods: Data of 49 women who underwent pelvic MRI before and after UAE were retrospectively reviewed. Uterine and leiomyoma volumes, ADC values of leiomyomas, and normal myometrium were calculated before and after UAE., Results: By comparison with baseline ADC values, a significant drop in leiomyoma ADC was found at 6-month post-UAE (1.096 × 10(-3) mm(2)/s vs. 0.712 × 10(-3) mm(2)/s, respectively; p < 0.0001), but not at 48-h post-UAE. Leiomyoma devascularization was complete in 40/49 women (82 %) at 48 h and in 37/49 women (76 %) at 6 months. Volume reduction and leiomyoma ADC values at 6 months correlated with the degree of devascularization. There was a significant drop in myometrium ADC after UAE. Perfusion defect of the myometrium was observed at 48 h in 14/49 women (28.5 %) in association with higher degrees of leiomyoma devascularization., Conclusion: Six months after UAE, drop in leiomyoma ADC values and volume reduction correlate with the degree of leiomyoma devascularization. UAE affects the myometrium as evidenced by a drop in ADC values and initial myometrial perfusion defect., Key Points: • A drop in leiomyoma ADC values is observed 6 months after UAE. • Drop in leiomyoma ADC value is associated with leiomyoma devascularizarion after UAE. • MR 48 h post-UAE allows assessing leiomyoma devascularization. • Myometrium perfusion defect occurs more often in women with a smaller uterus.

Uterine leiomyomata present major problem for females. Although they are benign tumors their frequency is associated with many symptoms like infertility, abdominal pain, menorrhagia. Authors based on their own morphological studies and review of the literature try to indicate main factors causing angiogenesis within leiomyomata and its influence on tumor growth. The strongest proangiogenic factor seems to be hypoxia, which stimulates up- and down-regulation of numerous genetically determined substances. Also mechanical pressure acting upon newly growing vessels is one of the factors which may determine formation of so called "vascular pseudocapsule" around the lesion.

Objective: The principal objective of this study was to use contrast-enhanced ultrasonography to describe the characteristics of fibroid microvascularization before and after embolization., Study Design: Forty women had contrast-enhanced ultrasonography with Sonovue(®) injections before uterine artery embolization, the day afterwards, and at 6-12 months afterwards. An MRI was also performed before and after the procedure., Results: Two thirds of the fibroids took up the contrast product before the myometrium did, and 45.8% were vascularized along the peripheral rim of the fibroid, compared with 41.6% with a principal pedicle and from the center in three (12.6%). After embolization at day one (D1), the myometrium was fully enhanced, that is, perfusion of the myometrium was plainly visible, in 25 cases (69.4%; n=36), partially enhanced in eight (22.2%), and totally avascular in three (8.4%). Analysis of the failures according to imaging criteria the day after embolization (D1) showed failure in seven women, with partial enhancement for six, and total for one. In the imaging at 6 months (M6), contrast ultrasonography showed failure for three women, with enhancement of the largest fibroid. This enhancement was total in two cases and partial (40%) in one. There were five failures according to MRI at M6, with partial enhancement. Only two of these failures were simultaneously failures according to the contrast-enhanced ultrasonography. There were five clinical failures, two consistent with the imaging at 6 months and four predictable on D1., Conclusion: Contrast-enhanced ultrasonography is feasible and useful to understand fibroid vascularization and for monitoring embolization; its correlation with MRI is good, its concordance less so., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The pseudocapsule (PC) of the uterine leiomyoma (UL) is an anatomic entity that surrounds the myoma separating it from the myometrium (UM). Although a number of microarray experiments have identified differences in gene expression profile in the UL when compared with the UM, there is a lack of systematic studies on the PC. In this study, quantitative RT-PCR analysis was performed on 18 matched PC, UL and UM specimens and results showed that the PC displays a specific gene expression profile. The low expression level of insulin-like growth factor (IGF-2), a fibroid specific marker, that we found in the PC and the UM when compared with the UL, clearly indicates that the PC is in structural continuity with the UM. However, the significant increase in endoglin expression level in PC with respect to the UL and UM indicates that an active neoangiogenesis is present in PC. Conversely, other angiogenic factors such as von Willebrand factor (vWF) and vascular endothelial growth factor A (VEGF-A) seem to have little influence on the PC angiogenesis. Because the endoglin is preferentially expressed in proliferating endothelial cells, whereas the vWF and VEGF-A are preferentially expressed in preexisting endothelial cells, our idea is that the angiogenic activity in the PC is linked to wound healing. The angiogenic activity is also sustained by intermediate expression level of cystein-rich angiogenesis inducer 61, connective tissue growth factor and collagen 4α2 genes all involved in the neoangiogenesis, that we detected in the PC. Taken together our data demonstrate that the specific expression pattern observed in the PC could be the response of the uterine wall's smooth cells to the tension imposed by the tumor. As a consequence, a neovascular structure is generated involving regenerative processes. For these reasons, we suggest that the laparoscopic intracapsular myomectomy (LIM), a new surgical technique that preserves the PC during the UL removal, should always be preferred, to favor a faster and proper uterine healing.

Aim: The main goal of this study was assessment of vascular structure of uterine leiomyomata localized between outer myometrium and endometrium., Materials and Methods: The study was carried out on thirty two human uteri collected upon autopsy. Vessels were injected with synthetic resin, next corroded and coated with gold, finally observed using scanning electron microscope. Next ten uteri were injected with acrylic emulsion and studies using immunohistochemical staining for von Willebrandt's factor., Results: Vascular structure of outer myometrial leiomyomata was quite similar to those observed in the middle of muscular layer of uterus, characterized by relatively dense 'vascular capsule', consisted of flattened vein, arterioles and capillaries., Conclusions: Structure of outer myometrial uterine leiomyomata was similar to those observed during growth within myometrium.

Objective: To allow a morphological evaluation of pseudocapsule vasculature of uterine leiomyomas (ULs)., Design: Preliminary prospective study., Setting: University-affiliated hospitals., Patients: Ten women with symptomatic myomas warranting laparotomic hysterectomies., Methods: Pseudocapsules of ULs were isolated from the surrounding myometrium, for a digital reconstruction of pseudocapsule vessels and analysis by three-dimensional structure applying the Allen-Cahn mathematical model. The images were converted in a matrix and an appropriate created software elaborated the images. The "nonlocal" Allen-Cahn mathematical model was applied to reduce the image noise and to regulate vessel outlines obtaining a "clean" image., Main Outcome Measures: The geometrical characteristics and morphology of vessel pseudocapsule network of ULs., Results: The disarray in vascular architecture was evident from the absence of vessel parallelism and variable intervascular distances. An abnormal vascular branching of pseudocapsule was indicated by the different density of vessels per space and some vascular walls without interruption indicated vessel tortuosity. There were vascular spaces, which did not communicate with other vessels ("cul-de-sac" vessels)., Conclusions: Pseudocapsule vasculature showed increase of tortuosity, disarray, abnormal branching and the presence of "cul-de-sac" vessels. Three-dimensional reconstruction of leiomyoma pseudocapsule vasculature network, despite the benign nature of ULs, showed geometrical characteristics of malignant neoplasm vessels., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Purpose: To document immediate and short-term changes in uterine perfusion after uterine artery embolization (UAE)., Materials and Methods: Fifteen patients (median age, 42 years) underwent UAE with tris-acryl gelatin microspheres and a limited embolization protocol. Contrast-enhanced magnetic resonance imaging was performed before therapy and 1 hour (immediate), 48-72 hours (subacute), and a median of 5 months (short-term follow-up) after UAE to determine uterine and leiomyoma perfusion. Leiomyomas with a minimum diameter of 10 mm were included. Changes in regional (ie, fundus/body/cervix), zonal (ie, endometrium/inner/middle and outer myometrial layer), and leiomyoma perfusion were documented., Results: UAE was technically successful in all patients. Immediate contrast-enhanced MR imaging revealed ischemia of the uterine body and fundus. The endometrium and inner myometrial layer was involved in all 15 patients; the middle layer was also involved in 13. Ischemic defects were seen in the outer layer in one patient but never in the cervix. Subacute follow-up showed reperfusion of the myometrium in 73% of patients. Ischemic defects occurred in the endometrial and junctional zone in four patients and in the middle zone in one. Five-month follow-up showed perfusion of all uterine layers in all patients. Ten patients had complete infarction of all leiomyomas; five presented with 11 partially perfused leiomyomas., Conclusions: Limited bilateral UAE leads to transient uterine ischemia, particularly involving the endometrium and inner and middle zone of the myometrium of the uterine body and fundus. The cervix and subserosal layer are spared. Complete reperfusion of myometrial tissue is observed within 48-72 hours in most cases, whereas ischemic leiomyomas undergo irreversible infarction., (Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.)

The purpose of the study was to evaluate uterine ischaemia after uterine artery embolisation (UAE) using magnetic resonance imaging and the role of myometrial and fibroid ischaemia in the pathogenesis of post-procedural pain. T1-weighted gradient echo imaging before and after contrast agent was performed on 62 women before and 24 h after UAE. We assessed the severity (mild, moderate, severe) of myometrial ischaemia, and the percentage and volume of ischaemic tissue in myometrium and fibroids. The Verbal Rating Scale was used to assess in-hospital post-procedural pain (1-3 mild, 4-6 moderate, 7-10 severe). Mean maximal pain was 7.7. Myometrial ischaemia was mild, moderate and severe in 29, 23 and 10 patients, respectively. Moderate or severe myometrial ischaemia (p = 0.041), the percentage (p = 0.037) and volume (p = 0.012) of ischaemic tissue in the myometrium, and a large volume of embolic material (p = 0.038) correlated with severe pain. In summary, pain following UAE is common and partly explained by myometrial ischaemia.

Objective: Myoma therapy by uterine artery occlusion using laparoscopic ligation (UAOL) has been performed for many years and has proven effective, but limited information is available on its therapeutic mechanism. To examine this issue, we conducted this study to investigate the morphological change and apoptosis occurring in myomal and adjacent myometrial tissues shortly after UAOL., Study Design: In total, 16 myomas and adjacent myometrium were obtained from 7 cases before and at various points after artery ligation. The tissues were stained using hematoxylin and eosin for morphological observation. To investigate the existence of apoptosis, in situ immunostaining of Caspase 3 and TUNEL assay were performed. Cytochrome C released from mitochondria was also detected by immunohistochemistry., Results: Microscopic observation found that after UAOL, both myometrial and myomal tissues were edematous and apoptotic cells were widespread in both tissues. TUNEL assays showed that before UAOL, numbers of apoptotic cells in myomal and myometrial tissues had no significant differences (P=0.866). After ischemia of (36.69+/-18.53) min, apoptosis was significantly more elevated in myoma than in myometrium ((6.43+/-4.38)/10 HPF vs. (2.74+/-1.95)/10 HPF, P=0.003). Caspase 3 stain shared similar features with the TUNEL assay. In both groups cytochrome C was released from mitochondria after UAOL, and more was detected in the myoma., Conclusion: UAOL is an alternative method to treat symptomatic uterine myomas. Apoptosis via mitochondrial pathways may lead to reduction of the volume of myoma and myometrium and eventual relief of symptoms.

Objective: The objective of the study was to quantify markers of myometrial ischemia, necrosis, and inflammation in women undergoing uterine artery embolization (UAE)., Study Design: Women with symptomatic fibroids were randomized to treatment with UAE (n = 14) or abdominal myomectomy (n = 11). Peripheral venous blood samples were taken before and after the procedure, at 24 hours and 6 weeks. Creatine kinase (CK) and ischemia-modified albumin (IMA) were measured as markers of necrosis and ischemia. Inflammation was assessed by measurement of C-reactive protein (CRP)., Outcome Measures: Changes in the markers following UAE and myomectomy were measured., Results: Following UAE, no change was seen in CK or IMA, but CRP was raised only at 6 weeks. At 24 hours after myomectomy, there were significant rises in all 3 markers, with a return to normal by 6 weeks., Conclusion: No significant ischemia or necrosis occurs in the myometrium following UAE, whereas the delayed rise in CRP is likely to reflect necrosis in fibroids.

Background: The human uterine vasculature is highly structured, exhibiting circumferential and radial branching. Previously published angiograms of the arterial network describe a system of regular coils. Uterine fibroids lack this structured vasculature. In this study, we make a comparison between the vasculature in normal myometrium and in fibroids using robust stereological methods thus far lacking in the literature., Methods: Stereological and morphometric analysis of the vascular system was carried out on 15 normal and 27 small fibroid (5-40 mm) uteri taken from women suffering menorrhagia. Projected images of published angiograms were also re-examined, measuring tortuosity., Results: A decreasing gradient of vascular smooth muscle from outer to inner myometrium was found in normal uteri, with no corresponding gradient in capillary tissue fraction. An association between vascular luminal size, amplitude and frequency of vessel bending was also established. Conversely, fibroids were found to lack structured or muscularized vasculature., Conclusions: A quantitative gradient within the myometrial vascular system, which is absent in fibroids, has been demonstrated. These structural differences between diseased and healthy tissues are probably because of differing expression of angiogenic growth factors and may explain the distribution of particles seen after uterine artery embolization.

Objectives: To quantitatively examine differences in microvascular density between fibroid and myometrial tissue from fibroid uteri removed at hysterectomy, both before and after the menopause, and with hormone replacement therapy., Methods: Factor VIII immunostaining of formalin fixed tissues was used to identify blood vessels, and the vessels counted by an investigator blinded to tissue type or menopausal status., Results: The mean myometrial: fibroid MVD ratio was 2.38 higher in the post-menopausal group (95% CI: 0.12, 4.65, p=0.0474) than in the pre-menopausal group, with the hormone therapy (HT)-using post-menopausal group lying in between. An increase in microvascular density in the myometrium after the menopause was responsible for most of the change in ratios seen between the pre and post-menopausal pairs. There was a trend to increasing myometrial MVD with increasing number of years post-menopause., Conclusions: Myometrial microvascular density increases markedly after the menopause, while fibroid microvascular density does not alter. Thus, the difference between myometrial and fibroid vasculature becomes greater after the menopause. The implications of this for the treatment of fibroids in post-menopausal women is discussed.

This study aimed to compare vascular parameters between fibroid and myometrium. From 10 uteri, specimens were taken from small fibroids (<0.5 cm), from the inner and outer parts of large fibroids (>3 cm), and from myometrium. Antibodies to endothelial cell markers CD31, CD34, factor VIII-related antigen (FVIII), and Ulex europaeus lectin were used in routine immuno- and lectin chemistry protocols. Parameters calculated were vascular area (VA), microvascular density (MD) and vascular luminal diameter. VA measures showed that myometrium had a greater area stained than small fibroids (P = 0.03) using CD31 and both inner (P = 0.04) and outer (P = 0.01) regions of large fibroids using FVIII, and than all groups (small, P = 0.02; inner, P = 0.02; outer, P = 0.006) using the lectin U. europaeus. MD was higher in myometrium than all uterine fibroid groups (small, P = 0.009; inner, P = 0.01; outer, P = 0.01) using U. europaeus lectin, than both regions of large (inner, P = 0.04; outer, P = 0.02) fibroids using FVIII, and than outer regions of large fibroids using CD31 (P < 0.05). There were significantly larger diameter vessels in myometrium and large fibroids compared with small fibroids using CD34, FVIII and the lectin U. europaeus (P

With scanning and transmission electron microscopy characteristic changes in the endothelial lining of myometrial vessels of uterus affected with myoma were revealed. In the presence of longitudinally oriented folds and microgrowths on the luminal surface in a healthy myometrial part, a number of changes were observed in the myoma vessels. These included the disappearance of cell surface derivatives, disturbance of tight junction of endothelial cells borders, the rise of cells over the endothelial monolayer and formation of crateriform pits. The partition of the endothelial cells on myoma vessels was accompanied by the disturbance of the microvesicular transendothelial transport.

Histological, morphometric and histochemical examination of uterine samples was carried out in 33 cases of intramural myoma (aged 26-45) and 32 autopsied controls with unaltered uterus (20-45 years). Peripheral areas of myomas showed a polymeric-homonomous structure of the blood microcirculatory bed. However, it was characterized by higher specific volumes of all components as compared to controls. This, perhaps, may account for local circulatory hyperestrogenism which supports myoma progression. Pronounced changes in the structure of microvessels of the central areas were matched by a 2-4-fold decrease in their specific volumes. The degree of said alteration in other areas of the myometrium was found to be in direct correlation with the size of myoma.

Regional blood flow in the myometrium and myomata has been measured during laparotomy in 11 patients using locally injected 133Xenon. Blood flow was calculated from the wash-out curves using both initial slope technique and compartment analysis. Assuming equal partition coefficients in myometrium and myomata the following values in ml-min-1-100 g-1 are seen: initial slope technique-myometrium 15.6 +/- 2.29, myomata 5.1 +/- 0.95, compartment analysis-myometrium 20.01 +/- 3.21, myomata 5.5 +/- 1.16. The blood flow was always lower in myomata than in myometrium of the same uterus. The main reason for the reduction of blood flow per unit weight of uterus in patients with myomata previously reported thus seems to be low blood flow in the myomata. A slight reduction of blood flow in the surrounding myometrium, however, also seems probable.