The use of super-selective uterine artery branch embolization and methotrexate in cervical pregnancy - case reports and literature review.

Cervical ectopic pregnancy (CEP) is one of the rarest types of ectopic pregnancy. Early detection of such cases increases the chances of conservative treatment and fertility preservation. Within 6 weeks of each other, 2 women were admitted to the OB/GYN Department with cervical ectopic pregnancies. They were successfully treated with a double dose of methotrexate and super-selective uterine artery branch embolization (SUABE). Taking into account health and economic considerations, for instance the optimal recovery time, and lower costs of operating theater time, laboratory testing and outpatient observation, it seems that safe, minimally invasive, fertility-saving, effective systemic administration of MTX in combination with SUABE, can be a rational alternative to cervical ectopic pregnancy treatment.

Pessary for Management of Cervical Varices Complicating Pregnancy.

BACKGROUND: Cervical varices complicating pregnancy are rare but can cause significant maternal and perinatal morbidity. There is limited evidence regarding the optimal management of bleeding caused by cervical varices during pregnancy. CASE: A 38-year-old woman was admitted to the hospital at 16 weeks of gestation due to vaginal hemorrhage in the setting of cervical varices accompanied by placenta previa. A cervical pessary was placed at 21 weeks of gestation without further bleeding. Magnetic resonance imaging demonstrated variceal reduction after pessary placement, and a cesarean delivery was performed at 36 weeks of gestation without complications. CONCLUSION: Cervical pessary should be considered as conservative option to control the bleeding associated with cervical varices during pregnancy.

The role of semiquantitative evaluation of lympho-vascular space invasion in early stage cervical cancer patients.

OBJECTIVE: Lymph vascular space involvement (LVSI) is one of the most important prognostic factors in early stage cervical cancer. Its qualitative evaluation represents a milestone for patient risk stratification and treatment choice, but a semi-quantitative analysis of LVSI may offer a more truthful risk model, as already demonstrated for endometrial cancer. The present study aims to investigate the performances of a semi-quantitative evaluation of LVSI in terms of patient risk assessment. METHODS: In this retrospective study were enrolled patients underwent surgical treatment for early cervical cancer from January 2009 to October 2018. A semi-quantitative evaluation such as the "three-tiered approach" was used to classify the LVSI pathway: negative vs. focal vs. diffuse. RESULTS: Diffuse LVSI was found to be a risk factor for lymph node metastasis (OR: 9.844, p < 0.001), and parametrial involvement (OR: 5.566, p < 0.001). Lymph nodal recurrences were more frequent in diffuse LVSI group (LVSI negative vs. focal LVSI p = 0.369; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.214); and so distant recurrences (LVSI negative vs. focal LVSI p = 0.623; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.026). Patients with diffuse LVSI showed a worse disease-free survival (DFS) than patients with focal or absent involvement (DFS LVSI negative vs. focal LVSI p = 0.938; LVSI negative vs. diffuse LVSI p < 0.001; focal LVSI vs. diffuse LVSI p = 0.036). CONCLUSION: Semi-quantitative evaluation of LVSI may be useful to identify risk patients for shorter disease-free survival and lymphatic and distant recurrences in patients with early stage.

Noninvasive, in vivo assessment of the cervical microcirculation using incident dark field imaging.

AIM: This study evaluates the feasibility of handheld vital microscopy for noninvasive, objective assessment of the microcirculation of the human uterine cervix. We qualitatively and quantitatively describe the microcirculation in healthy subjects in order to provide a basis for its application in cervical pathology. METHODS: Incident dark field imaging was used to image the microcirculation in four quadrants of the uterine ectocervix in ten healthy participants. If the squamocolumnar junction was visible, measurements were repeated on the endocervical columnar epithelium as well. Image acquisition time was recorded and participants scored the experienced level of discomfort. Angioarchitecture was classified according to Weber's classification. Quantitative parameters included capillary density (CD), total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI). RESULTS: Image acquisition was easy, fast and well tolerated. Angioarchitecture was characterized by two distinctive and organized patterns; capillary loops underneath the squamous epithelium of the ectocervix and vascular networks underneath the columnar epithelium. In the image sequences containing capillary loops, mean CD was 33.2 cpll/mm2 (95% CI 28.2-38.2 cpll/mm2). In the image sequences with vascular networks, mean TVD was 12.5 mm/mm2 (95% CI 11.2-13.77 mm/mm2), mean PVD was 12.2 (95% CI 11.0-13.5 mm/mm2), MFI was 3 and PPV was 100%. CONCLUSIONS: Incident dark field imaging allows for noninvasive, real time visualization and objective evaluation and quantification of the microcirculation of the uterine cervix. The organized vascular patterns and optimal perfusion observed in healthy subjects allow for comparison with cervical pathology, for example in patients with cervical dysplasia or cervical cancer.

Assessment of cervical volume and spectral Doppler parameters in tumour dominant vessel of patients with locally advanced squamous cell cervical carcinoma.

We evaluated cervical volume and spectral Doppler parameters: peak systolic velocity (PSV), resistance index (RI) and pulsatility index (PI) in the tumour dominant vessel of 50 patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB and their changes during treatment. The patients underwent transvaginal Doppler ultrasonography prior to treatment, after external beam radiation therapy (EBRT) and 6 weeks after brachytherapy. Radiotherapy decreased cervical volume and PSV values of the tumour dominant vessel. The PSV values before EBRT in G1 + G2 tumours were higher than in G3 tumours. No correlations between cervical volume, PSV, RI and PI values with disease-free survival (DFS) and overall survival (OS) were found. We concluded, that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results. Spectral Doppler parameters PSV, RI and PI of tumour dominant vessel did not predict prognosis for these patients.Impact StatementWhat is already known on this subject? Transvaginal Doppler sonography is considered as a useful diagnostic method in patients with cervical carcinoma. However, despite numerous studies, the value of spectral Doppler parameters in tumour dominant vessel and cervical volume of patients with locally advanced cervical SCC is still not well defined.What the results of this study add? In our prospective study, we found that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results and spectral Doppler parameters of tumour dominant vessel did not predict prognosis for these patients.What the implications are of these findings for clinical practice and/or further research? Our study underlines the limited value of spectral Doppler technique in patients with cervical carcinoma. Further research should be focussed on identifying and validating novel prognostic and predictive factors.

A new non-invasive procedure for refractory PPH after vaginal delivery and caesarean section.

Worldwide, the incidence of postpartum haemorrhage (PPH) is ∼6% and it is the leading cause of maternal mortality. The present study introduces a non-invasive procedure called bilateral cervix apex clamping (BCAC) as a new treatment for refractory PPH. A total of 13 vaginal deliveries and 5 caesarean section patients received the BCAC procedure to stop bleeding. During the procedure, the anterior and posterior walls of the cervical apex were clamped using toothless ovum forceps from the left and right side. The procedure was terminated when the bleeding had nearly stopped without clamping. The success rate of the procedure was 94.4% (17/18) overall, and 92.3% for vaginal delivery and 100% in caesarean section patients. Only one case of vaginal delivery did we resort to exploratory laparotomy and hysterectomy as amniotic fluid embolism occurred. The time spent on the procedure was 2-4 min for vaginal delivery cases and 5-7 min for caesarean section patients. The blood loss reduced significantly after the procedure, before the BCAC and after it was 875(450) ml versus 100(80)ml (p < .0001). There was a reduction in the need for UAE (uterine artery embolisation) from 13 in 22,817 deliveries (2013-2015) to 0 in 18,212 deliveries (2016-2017 (p < .001). But no change in the rate of hysterectomy (5/22817 versus 5/18212) (p = .76). BCAC is a simple, easy, safe, effective and non-invasive procedure that can decrease bleeding in patients with PPH.Impact statementWhat is already known on this subject? The BCAC clamping procedure was first described in Russia 80 years ago as the Genkel-Tikanadze method. But a PUBMED search did not identify and previous studies published on use of the technique.What do the results of this study add? The results of this study show that the BCAC clamping procedure can reduce bleeding significantly in refractory postpartum haemorrhage, when the uterine body is well contracted. The procedure can be performed after both in vaginal delivery and caesarean section. It can also reduce the necessity for UAE and balloon tamponade.What are the implications of these findings for clinical practice and/or further research? BCAC can be used after the failure of regular first line therapy for postpartum haemorrhage.

Efficacy of Surface-Modified PLGA Nanoparticles as a Function of Cervical Cancer Type.

PURPOSE: Hypovascularization of cervical tumors, coupled with intrinsic and acquired drug resistance, has contributed to marginal therapeutic outcomes by hindering chemotherapeutic transport and efficacy. Recently, the heterogeneous penetration and distribution of cell penetrating peptide (CPP, here MPG) and polyethylene glycol (PEG) modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were evaluated as a function of tumor type and morphology in cervical cancer spheroids modeling hypovascularized tumor nodules. Building upon this work, this study investigates the efficacy imparted by surface-modified Doxorubicin-loaded NPs transported into hypovascularized tissue. METHODS: NP efficacy was measured in HeLa, CaSki, and SiHa cells. NP internalization and association, and associated cell viability, were determined in monolayer and spheroid models. RESULTS: MPG and PEG-NP co-treatment was most efficacious in HeLa cells, while PEG NPs were most efficacious in CaSki cells. NP surface-modifications were unable to improve efficacy, relative to unmodified NPs, in SiHa cells. CONCLUSIONS: The results highlight the dependence of efficacy on tumor type and the associated microenvironment. The results further relate previous NP transport studies to efficacy, as a function of surface-modification and cell type. Longer-term, this information may help guide the design of NP-mediated strategies to maximize efficacy based on patient-specific cervical tumor origin and characteristics.

Cervical artery dissection: fibromuscular dysplasia versus vascular Ehlers-Danlos syndrome.

We report the case of a 42-year-old patient referred for suspicion of fibromuscular dysplasia in the context of a carotid artery dissection occurring after a minor trauma. Initial complaints included left hemicrania, lateral diplopia with left 6th cranial nerve palsy and pulsatile tinnitus. The work-up disclosed a large left carotid-cavernous fistula, as well as more proximal carotid lesions compatible with multifocal fibromuscular dysplasia. Personal history included colonic and uterine perforation. Family history disclosed a fatal hemorrhage due to rupture of a splenic artery aneurysm in the father and an iliac dissection in the sister. Genetic screening revealed a mutation in exon 6 of the COL3A1 gene in the index patient and her sister, confirming the diagnosis of vascular Ehlers-Danlos syndrome (vEDS). This case report shows that images suggestive of fibromuscular dysplasia may be found in patients with demonstrated vEDS. Furthermore, it reminds that in case of cervical artery dissection occurring in a young patient, all efforts should be made to diagnose the underlying condition. In particular, the existence of a family history of arterial dissection, the occurrence of a carotid-cavernous fistula and coexistence with other complications suggestive of a connective tissue disease should prompt physicians to consider the diagnosis of vEDS.

Cervical varices unrelated to placenta previa as an unusual cause of antepartum hemorrhage: A case report and literature review.

OBJECTIVE: Ruptured cervical varicose veins can cause significant vaginal bleeding during the third trimester of pregnancy. The etiology is not uncommon, yet receives little discussion in current literature. We here report such a case with complete evaluations, managements and follow ups; while analyzing similar cases published. CASE REPORT: A 34-year-old pregnant woman, gravida 1, presented with sudden onset of painless antepartum hemorrhage at 31+5 weeks of gestation. Speculum examination revealed ruptured cervical varicose veins; further evaluations with transvaginal sonography and magnetic resonance imaging were done to study the extensiveness and characteristics of the lesion. The cervical varices spontaneously regressed by postpartum day 4 and no recurrence was observed in the immediate postpartum follow-up period or in the subsequent pregnancy. CONCLUSION: The case is unique for the lack of association with placenta previa. Cervical varicose veins rupture should be considered for painless vaginal bleeding during the third trimester pregnancy.

Cervical varices: An unusual source of first-trimester hemorrhage.

Endocervical varices are a rare cause of obstetrical hemorrhage. Usually presenting in the second and third trimesters, bleeding varices often require pregnancy termination or indicated preterm birth via cesarean delivery. Our patient experienced variceal hemorrhage at 12 weeks' gestation in a dichorionic twin pregnancy conceived through in vitro fertilization. A low-lying placenta resolved at 19 weeks followed by variceal regression at 22 weeks' gestation. Endocervical varices causing first-trimester hemorrhage may regress with resolution of a coexisting low placental implantation, permitting planned vaginal delivery, despite progressive hemodynamic changes of pregnancy. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:218-221, 2018.

A study on uterine lymphatic anatomy for standardization of pelvic sentinel lymph node detection in endometrial cancer.

OBJECTIVE: To describe the anatomy of uterine lymphatic drainage following cervical or fundal tracer injection to enable standardization of a pelvic sentinel lymph node (SLN) concept in endometrial cancer (EC). METHODS: A prospective consecutive study of women with EC was conducted. A fluorescent dye (Indocyanine green) was injected into the cervix (n=60) or the uterine fundus (n=30). A systematic trans- and retroperitoneal mapping of uterine lymphatic drainage was performed. Positions of the pelvic SLNs, defined by afferent lymph vessels, and lymph node metastases were compared. RESULTS: Two consistent lymphatic pathways with pelvic SLNs were identified irrespective of injection site; an upper paracervical pathway (UPP) with draining medial external and/or obturator lymph nodes and a lower paracervical pathway (LPP) with draining internal iliac and/or presacral lymph nodes. Bilateral display of at least one pelvic pathway following cervical and fundal injection occurred in 98% and 80% respectively (p=0.005). Bilateral display of both pelvic pathways occurred in 30% and 20% respectively (p=0.6) as the LPP was less often displayed. Nearly one third of the 19% node positive patients had metastases along the LPP. No false negative SLNs were identified. CONCLUSIONS: Based on uterine lymphatic anatomy a bilateral detection of at least one SLN in both the UPP and LPP should be aimed for. Absence of display of the LPP may warrant a full presacral lymphadenectomy. Although pelvic pathways and positions of SLNs are independent of the tracer injection site, cervical injection is preferable due to a higher technical success rate.

Spectral CT imaging in cervical computed tomography angiography: comparison of spectral CT monochromatic imaging and conventional CT polychromatic imaging.

OBJECTIVE: To compare the image quality of spectral CT monochromatic imaging and conventional CT polychromatic imaging for analysing CTAs in patients with cervical cancer. METHODS: In this IRB approved prospective study, 60 patients who had been diagnosed with cervical cancer underwent pelvic arterial CTA between May 2013 and July 2013. They were randomly divided into two groups; one group (30 patients) received 120 kVp polychromatic imaging (conventional CT group) and the other group (30 patients) received spectral CT imaging (spectral CT group), while all patients in both the groups received injections of 1 ml/kg of contrast agent. A total of 101 sets of monochromatic images (40-140 keV) were obtained via data reconstruction in the spectral CT group, and the monochromatic images with the best contrast-to-noise ratio (CNR) between the common iliac artery and pelvic fat (i.e. the best monochromatic energy) were selected. The best monochromatic images for the spectral CT group and the polychromatic images for the conventional CT group were postprocessed and visualised in MIP, VR and CPR mode. The CT attenuation value, noise and CNR of bilateral common iliac arteries were measured with the best monochromatic energy, as well as with 70 keV, in the spectral CT group and in the conventional CT group. The quality of the CT images was evaluated with a 5-point scale. The CTDIvol and the dose-length product (DLP) of the two groups were measured, and the results were statistically analysed. RESULTS: When images were at 50±1 keV, the common iliac artery and pelvic fat had the highest CNR, which was 72.00% higher than the images at 70 keV (P=.001) in the spectral group, and thus, the images at 50±1 keV were considered to have the best monochromatic energy. The average CT value of the internal iliac artery, which had the best monochromatic energy from the spectral CT group, was higher than that of the images from the conventional CT group (603.96±62.68 vs 251.24±28.77; P<.001), and the differences in the CNR (73.97±11.83 vs 45.21±16.63) and the subjective score (3.10±1.73 vs 2.80±1.63) were statistically significant (both P<.05). There were no significant differences in the CTDIvol (10.48±2.86 vs 12.38±1.88 mGy) or the DLP (317.76±95.50 vs 332.25±21.25 mGy cm) between the spectral and the conventional CT groups. CONCLUSION: Monochromatic spectral CT imaging has excellent soft tissue contrast and good spatial resolution and can visualise the arteries and branches supplying the tumours more clearly in patients with cervical cancer. Compared with polychromatic images, monochromatic spectral CT images are higher quality, which helps the treatment of patients with cervical cancer.

Intravoxel incoherent motion diffusion weighted MRI of cervical cancer - Correlated with tumor differentiation and perfusion.

OBJECTIVES: To investigate the value of parameters derived from IVIM model in grading of uterine cervical cancer and the relationship between perfusion parameters derived from IVIM and that from DCE-MRI. METHODS: Parameters of DWI (ADC, D, f, D*) and semi-quantitative parameters of DCE-MRI (Slop, Maxslop, CER, Washout, AUC90) were assessed in 24 female with cervical cancers. Except for ROIs encompassed all of the area of tumors in axial plane (A_all), ROIs on tumor edge (A_peri) and tumor center (A_central) were drawn. All of the parameters were compared among three pathology grades. Perfusion parameters derived from IVIM were correlated with that from DCE-MRI. RESULTS: For G1, G2 and G3 tumors, on tumor edge ADC=(1.03±0.11), (1.05±0.10), (0.90±0.05)×10(-3)mm(2)/s, D=(0.80±0.11), (0.78±0.07), (0.69±0.06)×10(-3)mm(2)/s, and f=(0.19±0.03), (0.22±0.02), (0.24±0.03). The differences among groups were significant (P<0.05). On tumor center, ADC=(0.90±0.10), (0.85±0.03), (0.80±0.07)×10(-3)mm(2)/s with significant differences (P=0.027). The other parameter, D and f of tumor center, as well as D* of all tumor areas, were of no statistic significance. Most of the DCE-MRI parameters negatively correlated with tumor volume. Although the correlation between f and slop was statistic significant, R=0.277 meant a negligible correlation. f had week correlation with Maxslop, CER and AUC90 (R=0.361, 0.400 and 0.405; P<0.001). D* showed no statistic significant correlation with all of the DCE parameters. CONCLUSION: IVIM model could possibly be used to evaluate tumor differentiation and perfusion, providing an alternative for DCE-MRI.

Assessment of uterine enhancement rate after abdominal radical trachelectomy using dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: The purpose of this study was to assess uterine enhancement rate after abdominal radical trachelectomy (ART) using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging. METHODS: Ten patients with early uterine cervical cancer, who were treated by ART, were included in this study. Each patient underwent DCE MR imaging using a 3 T unit to assess uterine enhancement rate at three times (before surgery and 1 and 3 months after surgery). The radiologist calculated mean signal intensities of the anterior and posterior myometrium and also measured the signal intensities of the urine in the bladder on the same image, which was expressed as the myometrium-to-urine signal intensity ratio. In the time-intensity ratio curve, enhancement parameters (peak signal intensity ratio and peak time) of the uterine body were compared across the three MR examinations. RESULTS: The peak signal intensity ratio was 6.96 ± 0.98 on MR examinations before surgery, 6.14 ± 0.81 1 month after surgery, and 6.26 ± 0.63 3 months after surgery (p = 0.069). The peak time was 57.6 ± 3.4 s on MR examinations before surgery, 56.4 ± 4.4 s 1 month after surgery, and 53.2 ± 8.0 s 3 months after surgery (p = 0.304). No significant differences were found in either the peak signal intensity ratio or peak time across the three MR examinations. CONCLUSIONS: That no significant decrease of uterine enhancement rate was found after surgery suggests the uterine function and fertility may be preserved after ART.

Bleeding after laparoscopic supracervical hysterectomy managed with cervical artery embolization. A case report.

BACKGROUND: Postoperative bleeding is a known complication after laparoscopic supracervical hysterectomy (LASH), and trachelectomy is the traditional management of significant bleeding. CASE: We present the case of a patient with significant postoperative bleeding 1 month after LASH, resulting in symptomatic anemia requiring blood transfusion. Gelfoam embolization of the bilateral cervical arteries was successful in stopping the bleeding. The patient had no further bleeding and had resolution of anemia at 6 months postprocedure. CONCLUSION: Our case demonstrates a successful multidisciplinary and minimally invasive approach to management of postoperative bleeding with bilateral cervical artery embolization and should be considered as a potential treatment option.

STRUCTURAL BASIS OF THE VASCULAR HEMOSTATIC MECHANISM IN THE UTERINE CERVIX.

The objective of the study was to investigate the angioarchitectonics and the functional morphology of the vessels of the cervix and to clarify the role of structural features of these vessels in preventing hemorrhaging in parturition during cervical dilatation. Cervixes uteri were obtained from corpses of 30 women of various ages and 5 ablated at labor. Series of histotopographical specimens of the cervixes were processed using histological and histochemical methods. Peculiar features of the angioarchitectonics, histotopography and structure of cervical vessels were encountered. Arteries penetrating the cervix are surrounded by tight muffs of anastomizing veins that are closely adjacent to the arteries. In other cases, the arteries are located within the lumen of veins--"vessels within vessels". Cervical arteries make up subendocervical convolutions. During pregnancy, smooth muscle "cushions" develop in the vessels. The cervix is pierced by a network of veins that divide the cervical tissue into separate stromal "lobules". This peculiar vascular architecture might be important structural basis of the vascular hemostatic mechanism in the neck of the uterus triggered by labor. It prevents vessel rupture, hemorrhaging and amniotic fluid and air embolism during cervical dilatation. The venous network that passes through the cervix makes it easy for the separate stromal "lobules" of the cervix to move relative to each other during cervical dilatation.

FSH receptor (FSHR) expression in human extragonadal reproductive tissues and the developing placenta, and the impact of its deletion on pregnancy in mice.

Expression and function of the follicle-stimulating hormone receptor (FSHR) in females were long thought to be limited to the ovary. Here, however, we identify extragonadal FSHR in both the human female reproductive tract and the placenta, and test its physiological relevance in mice. We show that in nonpregnant women FSHR is present on: endothelial cells of blood vessels in the endometrium, myometrium, and cervix; endometrial glands of the proliferative and secretory endometrium; cervical glands and the cervical stroma; and (at low levels) stromal cells and muscle fibers of the myometrium. In pregnant women, placental FSHR was detected as early as 8-10 wk of gestation and continued through term. It was expressed on: endothelial cells in fetal portions of the placenta and the umbilical cord; epithelial cells of the amnion; decidualized cells surrounding the maternal arteries in the maternal decidua; and the stromal cells and muscle fibers of the myometrium, with particularly strong expression at term. These findings suggest that FSHR expression is upregulated during decidualization and upregulated in myometrium as a function of pregnancy. The presence of FSHR in the placental vasculature suggests a role in placental angiogenesis. Analysis of genetically modified mice in which Fshr is lacking in fetal portions of the placenta revealed adverse effects on fetoplacental development. Our data further demonstrate FSHB and CGA mRNAs in placenta and uterus, consistent with potential local sources of FSH. Collectively, our data suggest heretofore unappreciated roles of extragonadal FSHR in female reproductive physiology.

DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase.

BACKGROUND: DUSP3 phosphatase, also known as Vaccinia-H1 Related (VHR) phosphatase, encoded by DUSP3/Dusp3 gene, is a relatively small member of the dual-specificity protein phosphatases. In vitro studies showed that DUSP3 is a negative regulator of ERK and JNK pathways in several cell lines. On the other hand, DUSP3 is implicated in human cancer. It has been alternatively described as having tumor suppressive and oncogenic properties. Thus, the available data suggest that DUSP3 plays complex and contradictory roles in tumorigenesis that could be cell type-dependent. Since most of these studies were performed using recombinant proteins or in cell-transfection based assays, the physiological function of DUSP3 has remained elusive. RESULTS: Using immunohistochemistry on human cervical sections, we observed a strong expression of DUSP3 in endothelial cells (EC) suggesting a contribution for this phosphatase to EC functions. DUSP3 downregulation, using RNA interference, in human EC reduced significantly in vitro tube formation on Matrigel and spheroid angiogenic sprouting. However, this defect was not associated with an altered phosphorylation of the documented in vitro DUSP3 substrates, ERK1/2, JNK1/2 and EGFR but was associated with an increased PKC phosphorylation. To investigate the physiological function of DUSP3, we generated Dusp3-deficient mice by homologous recombination. The obtained DUSP3-/- mice were healthy, fertile, with no spontaneous phenotype and no vascular defect. However, DUSP3 deficiency prevented neo-vascularization of transplanted b-FGF containing Matrigel and LLC xenograft tumors as evidenced by hemoglobin (Hb) and FITC-dextran quantifications. Furthermore, we found that DUSP3 is required for b-FGF-induced microvessel outgrowth in the aortic ring assay. CONCLUSIONS: All together, our data identify DUSP3 as a new important player in angiogenesis.

Normal reference of cervical blood perfusion in pregnancy.

OBJECTIVE: To develop normal reference of cervical blood perfusion in pregnancy by using 3D power Doppler-derived FMBV at 16 to 24 weeks gestation. MATERIAL AND METHOD: The present prospective cohort study recruited the normal singleton pregnant women at 16 to 24 weeks gestation who had antenatal care and midtrimester ultrasound screening at Ramathibodi Hospital between June and September 2012. Transvaginal ultrasound (TVU) measurements of cervical length (CL), cervical volume (CV), vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were performed. The pregnant women with multifetuses, severe fetal anomalies, unknown delivery status, abortion, stillbirth, and preterm birth were excluded from the present study. RESULTS: The authors recruited 168 cases but 25 cases were excluded. Only 143 cases were included into the study. The mean of gestational age at ultrasound examination and delivery was 21 and 39 weeks respectively. There were no perinatal morbidity and mortality in the present study. The average values of cervical profiles of CL, CV VI, FI, and VFI were 4.2 cm, 31.6 cm3, 6.4, 38.9, and 2.6 respectively. CONCLUSION: The normal reference of cervical blood perfusion in Thai pregnant women was established. The VI, FI, and VFI of the normal term singleton pregnancy at 16 to 24 weeks gestation were 6.4, 38.9, and 2.6 respectively.

Hemoglobin parameters from diffuse reflectance data.

Tissue vasculature is altered when cancer develops. Consequently, noninvasive methods of monitoring blood vessel size, density, and oxygenation would be valuable. Simple spectroscopy employing fiber optic probes to measure backscattering can potentially determine hemoglobin parameters. However, heterogeneity of blood distribution, the dependence of the tissue-volume-sampled on scattering and absorption, and the potential compression of tissue all hinder the accurate determination of hemoglobin parameters. We address each of these issues. A simple derivation of a correction factor for the absorption coefficient, µa, is presented. This correction factor depends not only on the vessel size, as others have shown, but also on the density of blood vessels. Monte Carlo simulations were used to determine the dependence of an effective pathlength of light through tissue which is parameterized as a ninth-order polynomial function of µa. The hemoglobin bands of backscattering spectra of cervical tissue are fit using these expressions to obtain effective blood vessel size and density, tissue hemoglobin concentration, and oxygenation. Hemoglobin concentration and vessel density were found to depend on the pressure applied during in vivo acquisition of the spectra. It is also shown that determined vessel size depends on the blood hemoglobin concentration used.