Transvaginal pulsed and color Doppler sonography for the evaluation of adenomyosis

In an earlier paper, we reported our scoring system for the diagnosis of adenomyosis by gray scale transvaginal sonography. In this study we evaluated 44 benign uterine masses (adenomyosis and myomas) and seven uterine malignancies. We used transvaginal color and pulsed Doppler imaging to determine whether this technique is useful to differentiate adenomyosis from uterine malignancies. The peak systolic velocity and the resistive index of intratumoral vessels were studied. The differences in these parameters for adenomyosis and uterine malignancies were statistically significant. Our results suggest that this technique is useful to differentiate adenomyosis from uterine malignancies.     

Use of colour and spectral Doppler ultrasound examination in gynaecology

Objective: To review and sum up the published literature on gynecological Doppler ultrasound examination. Methods: Publications on gynecological Doppler ultrasound examination already known by the author, publications found in the bibliographic database Medline, and publications found in the reference lists of available studies were read, and relevant information was extracted and summarized. Results: Reference data representative of normal findings at transvaginal color and spectral Doppler ultrasound examination of the uterine and ovarian arteries have been established in healthy pre- and post-menopausal women and in normal early pregnancies. Blood flow velocities in the uterine and ovarian arteries change during the normal menstrual cycle and are very different in pre- and post-menopausal women. Lower blood flow velocities and higher pulsatility index (PI) values have been recorded in the ovarian arteries after the menopause. Uterine artery blood flow velocities increase and uterine artery PI values and resistance index (RI) values decrease with gestational age in the first trimester. There is not yet an established role of the gynecological Doppler ultrasound examination in clinical practice. It remains unclear whether the gynecological Doppler ultrasound examination contributes substantially to the clinical management of early pregnancy complications or infertility problems, to the differential diagnosis of pelvic masses or uterine pathology. Conclusions: Large prospective studies-preferably randomized controled trials-are needed to determine the clinical value of the gynecological Doppler ultrasound examination. Copyright 1997 Elsevier Science Ireland Ltd.     

T cell responses to Mycobacterium bovis in red deer, a large animal model for tuberculosis

Uterine morphology assessed by transvaginal ultrasound and the hemodynamics of intratumoral vessels assessed by color Doppler ultrasound were prospectively correlated with the clinical outcome of 25 patients with trophoblastic tumors. Twenty patients were followed without treatment (observation group) and 16 achieved complete local resolution. The four subjects with local persistence were combined with five patients referred from other institutions and received chemotherapy (treatment group). In the observation group both techniques had 100% accuracy in predicting local resolution or local persistence. Persistence was predicted 1-3 weeks before the increase of beta-human chorionic gonadotropin (beta-hCG) levels, whereas resolution was observed up to 8 weeks before the disappearance of beta-hCG. In one patient normal uterine morphology and vascularization in the presence of elevated hCG levels was associated with extrauterine spread. In the treatment group, normal uterine ultrasound morphology and negative color Doppler results had 100% negative predictive value. False-positive results were observed in two cases. We conclude that ultrasound evidence of abnormal uterine morphology or persistent vascularization on color Doppler examination with persistent hCG levels is indicative of local persistence. Normal uterine morphology with negative color Doppler results may be associated with extrauterine spread.     

Intratumoral blood flow analysis in ovarian cancer: what does it mean?

The objective of this study is to evaluate the significance of intratumoral blood flow in ovarian cancer. Forty-seven patients with histologically proved ovarian cancer underwent transvaginal gray scale sonography, and color and Doppler sonography before surgery. Intratumoral blood flow velocity waveforms obtained from architecture within the tumor were recorded, and resistive index and peak systolic velocity were calculated. Neither resistive index values nor peak systolic velocity values differed significantly among the histological diagnoses, regardless of stage (including metastatic tumor) or morphologic classification of tumor. These results suggest that intratumoral blood flow analysis in ovarian cancer cannot provide information on individual tumor characteristics.     

Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma

Vascular endothelial growth factor (VEGF) expression, vascularisation and tumour cell proliferation were analysed in 91 human epidermoid lung carcinomas using immunohistochemistry. A polyclonal anti-VEGF antibody was used for VEGF expression, a polyclonal antibody directed against human von Willebrand factor (factor VIII) to identify blood vessels and the proliferating cell nuclear antigen (PCNA) as a marker for proliferating cells. Positive staining for VEGF was obtained in 54 out of 91 cases (59%), the number of blood vessels varied from zero to 64 counts (mean 9.4) and the proportion of PCNA-positive cells varied from 1.3% to 72.1% (mean 25.2%). The mean PCNA labelling index and mean microvessel count in VEGF-positive tumours were significantly higher than those in VEGF-negative tumours (Wilcoxon rank sum test, P<0.0001; p<0.05). In addition, PCNA labelling index significantly increased with increasing VEGF expression (Jonckheere test, P<0.0001). In contrast, no association was found between PCNA labelling index and tumour vascularity (r=0.07, P=0.48). The close correlation of VEGF expression with tumour cell proliferation and microvessel density suggests that VEGF acts both as an autocrine growth factor and as stimulator for angiogenesis. However, tumour cell proliferation and microvessel growth and/or density may be regulated by separate mechanisms.     

Percutaneous ethanol injection under general anesthesia for hepatocellular carcinoma: 3 year survival in 112 patients

OBJECTIVE: The aim of this study was to determine whether the expression of thymidine phosphorylase by ovarian cancer cells correlates with the density of microvessels within the tumor, and with ultrasound-derived indices of blood flow. METHODS: Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were positive or negative for thymidine phosphorylase, the microvessel count and the peak systolic velocity (PSV). RESULTS: Forty-two tumors were studied (three of low malignant potential, 29 epithelial, four granulosa cell, two germ cell and four metastatic); 18 were stage I, six stage II, 11 stage III and three stage IV. Twenty-seven tumors (64%) were classified as thymidine phosphorylase-positive. The proportion of stage I tumors that was thymidine phosphorylase-positive (44%) was significantly lower (p = 0.022) than the corresponding value for stages II-IV (85%), but the values for microvessel count and PSV were similar. The microvessel count in thymidine phosphorylase-positive tumors was significantly higher than in thymidine phosphorylase-negative tumors (p = 0.005). Similarly, the PSV was significantly higher in thymidine phosphorylase-positive tumors (p = 0.009). There was a significant correlation between the microvessel count and the PSV (r = 0.354, p = 0.022). CONCLUSIONS: The expression of thymidine phosphorylase by malignant tumor cells is associated with an increase in microvessel density and PSV in patients with ovarian cancer.     

Interaction of dexamethasone and Salmonella enteritidis immune lymphokines on Salmonella enteritidis organ invasion and in vitro polymorphonuclear leukocyte function

OBJECTIVE: To evaluate the effects of gemeprost on utero-placental and luteal circulation and on the embryo/fetus in normal first trimester pregnancies. STUDY DESIGN: Sixty-seven women with a normal first trimester pregnancy requesting termination of pregnancy for psychosocial reasons were randomly allocated to pre-operative treatment with vaginal suppositories containing placebo or gemeprost. The women underwent transvaginal color and spectral Doppler ultrasound examination before the application of the suppository, 4 h after the application of the suppository but before the abortion, and on the seventh post-operative day. Blood flow velocities in the uterine and subchorionic arteries, the intrachorionic area and arteries in the wall of the corpus luteum and the embryonic/fetal heart rate were measured. RESULTS: The median value for pulsatility index (PI) in the dominant uterine artery was 2.4 before treatment with gemeprost and 8.5 4 h after treatment (P = 0.0006); the corresponding values for time-averaged maximum velocity (TAMXV) being 27 cm/s and 10 cm/s (P = 0.0006). Four (14%) of 28 embryos/fetuses in the gemeprost group were dead 4 h after treatment with gemeprost and the median heart rate of those still alive was significantly lower than before treatment (130 vs. 163 bpm; P = 0.003). In the placebo group, the results for the uterine arteries and the embryonic/fetal heart rate did not differ significantly between the first and second ultrasound examinations. The median values for PI and TAMXV in the arteries of the corpus luteum wall at the first ultrasound examination were 0.71 and 18 cm/s, respectively, in the placebo group and 0.71 and 20 cm/s, respectively, in the gemeprost group. These values remained almost unchanged at the second and third ultrasound examinations in both groups. CONCLUSION: Gemeprost has profound effects on utero-placental circulation in the first trimester and can induce embryonic/fetal bradycardia and sometimes embryonic/fetal demise. It has no unequivocal effect on luteal circulation.     

Hypertensive intra-arterial chemotherapy for endometrial carcinoma assessed by transvaginal Doppler ultrasound and magnetic resonance imaging

We examined the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using transvaginal Doppler ultrasound and magnetic resonance imaging. Angiotensin II, 100 mg cisplatin, and 40 mg doxorubicin were prescribed for 8 patients with endometrial carcinoma (3 stage Ia; 3 stage Ib; 2 stage II). The resistance index (RI) was obtained for intratumoral blood flow velocity waveforms by transvaginal Doppler ultrasound and changes in RI (delta RI: differences before and after chemotherapy) were calculated. The tumor volume (TV) was also evaluated, based on the T2-weighted image of magnetic resonance imaging (MRI). The decrease in tumor size [DR-T: (TV before chemotherapy--TV after chemotherapy)/TV before chemotherapy x 100] was determined. RI measurements did not correlate with TV, either before or after chemotherapy. The delta RI varied from 0.007 to 0.615 (mean: 0.207) and DR-T varied from 20.1% to 65.0% (mean: 45.5%). The correlation between delta RI and DR-T [DR-T = 23.5 + 167.2 (delta RI)-165.6 (delta RI)2; R2 = 0.772, p < 0.05] was significant. Therefore, we confirmed the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using both transvaginal Doppler ultrasound and MRI.     

Bacterial translocation and T-lymphocyte populations in experimental short-bowel syndrome

Ten patients with ovarian bleeding, who were surgically treated, had been preoperatively evaluated using transvaginal color Doppler ultrasound. The blood-flow velocity waveforms of the bleeding also were analyzed. The bleeding artery of the ovary was clearly detected in 9 of 10 (90%) patients by transvaginal color Doppler ultrasound and was later confirmed by either a laparotomy or laparoscopic surgery. Either a corpus luteum cyst or a ruptured corpus luteum was associated with the bleeding in the 9 of the 10 patients. The resistance-index value in each bleeding artery examined in the 9 cases was relatively low, ranging from 0.46 to 0.59 (mean: 0.51). Based on our findings, transvaginal color Doppler ultrasound is useful for preoperatively detecting bleeding arteries in clinically severe cases of ovarian bleeding.     

Septate uterus: detection and prediction of obstetrical complications by different forms of ultrasonography

The aims of the study were to compare the accuracy of transvaginal ultrasonography, transvaginal color Doppler sonography, hysterosonography, and three-dimensional ultrasonography in detection of septate uterus and to evaluate the occurrence of obstetrical complications in relation to septal dimension and vascularity. Each patient underwent transvaginal ultrasonography and color Doppler examination, whereas hysterosonography and three-dimensional ultrasonography were carried out in 76 and 86 patients, respectively. The sensitivity of different sonographic imaging modalities ranges between 95.21% and 99.29%. Color and pulsed Doppler sonographic studies of the septal area revealed vascularity in 71.22%. Patients with vascularized septa had a higher prevalence of obstetrical complications than those with avascularized septa (P < 0.05). Three-dimensional ultrasonography and hysterosonography are highly accurate diagnostic tools for detection of uterine septa. We found no correlation between septal dimension and rate of obstetrical complications, although pregnancy loss was most likely to occur in patients with vascularized septa.     

Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis

PURPOSE: To compare qualitative and quantitative magnetic resonance (MR) mammographic features of breast lesions with histopathologic findings, especially tumor angiogenesis. MATERIALS AND METHODS: Seventy-three patients (72 women, one man; aged 30-78 years; mean age, 51.0 years) with suspicious breast lesions underwent MR imaging. Noncontrast medium-enhanced localization imaging and then gadolinium-enhanced dynamic fast spoiled gradient-recalled-echo (SPGR) imaging were performed in all patients. In selected patients, subtraction fast SPGR images were obtained. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between enhancement parameters and microvessel determinations. RESULTS: Time intensity curve type correlated with microvessel density grade (Spearman rank correlation test: r = .90, P < .001). The steepest slope of contrast medium uptake correlated with microvessel counts (Pearson correlation test; r = .83, P < .001). Peripheral enhancement in invasive carcinomas (n = 9) correlated with high peripheral and low central microvessel densities, which were associated with desmoplasia and/or necrosis. Internal septations (n = 2) were seen only in fibroadenomas. CONCLUSION: The density and distribution of microvessels may play major roles in the determination of the initial rate of contrast medium uptake and the heterogeneity of tumor enhancement.     

Color Doppler ultrasound pulsatile flow signals of thoracic lesions: comparison of lung cancers and benign lesions

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p < 0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p < 0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p < 0.01; for PI, all p< or =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p > 0.05 for RI and PI), and even a significant difference from SCC (p < 0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.     

Placenta accreta: evaluation with color Doppler US, power Doppler US, and MR imaging

PURPOSE: To determine the value of transabdominal ultrasound (US), transvaginal US, color Doppler US, power Doppler US, and magnetic resonance (MR) imaging in the diagnosis of placenta accreta. MATERIALS AND METHODS: Nineteen patients in the third trimester of pregnancy who were at risk for placenta accreta underwent color Doppler and power Doppler US; 18 patients also underwent MR imaging. Images were interpreted prospectively for signs of accreta by two reviewers. The reviewers' confidence in their diagnosis was graded on a five-point scale. RESULTS: Outcomes at delivery were as follows: normal placenta (n = 11), hysterectomy owing to uncontrollable bleeding (n = 1), and placenta accreta (n = 7). Five cases of lower-uterine-segment placenta accreta were diagnosed with a high level of confidence with vaginal and power Doppler US. In one patient with a posterior placenta who had previously undergone myomectomy, MR imaging enabled the diagnosis of placenta accreta, which was not well depicted at US. CONCLUSION: In patients with a history of uterine scars, vaginal US with power Doppler US performed well in the evaluation of lower-uterine-segment placenta accreta. MR imaging depicts posterior placenta accreta.     

Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer

Vascular endothelial growth factor (VEGF) is a cytokine that is involved in tumor angiogenesis. Wild-type p53 (wt-p53) protein has been shown in cell lines to suppress angiogenesis through thrombospondin regulation. In this study, we immunohistochemically examined the expression of VEGF, nuclear and wild-type cytoplasmic p53, bcl-2, epidermal growth factor receptor, and c-erbB-2 oncoprotein; vascular grade; proliferation index; and extent of necrosis in non-small cell lung cancer (NSCLC). We analyzed 120 cases of early-stage NSCLCs (81 squamous cell carcinomas and 39 adenocarcinomas) treated with surgery alone (median follow-up, 63 months; range, 45-74 months). VEGF expression showed a positive association with high vascular grade (microvessel score of >75 per x250 field; P = 0.008), although about half of the LVG cases also expressed VEGF. None of the p53 antibodies examined correlated with angiogenesis. However, wt-p53 expression was inversely associated with VEGF expression, suggesting that wt-p53 is involved in the suppression of the VEGF gene. Combined analysis of VEGF, wt-p53, and microvessel counting showed that, although wt-p53 loss associates with VEGF switch-on, p53 protein may not be involved in the regulation of the angiogenic events downstream of VEGF expression. Moreover, no significant association of bcl-2 and c-erbB-2 oncoprotein expression with VEGF expression was observed. T/N stage, grade, Ki67 proliferation index, and extent of necrosis were not correlated with VEGF expression. Survival analysis showed that VEGF correlated with poor survival (P = 0.04) and was significant in node-negative cases (P = 0.03). We conclude that VEGF is an important angiogenic factor in NSCLC, its expression being dependent on wt-p53 loss.     

Angiogenic activity of cervical carcinoma: assessment by functional magnetic resonance imaging-based parameters and a histomorphological approach in correlation with disease outcome

Angiogenesis plays a fundamental role in tumor growth and metastasis. What is needed is a quantitative, noninvasive, and repeatable assay to estimate functional angiogenic activity of the entire tumor. The aims of the present study were to: (a) examine the relationship between functional magnetic resonance imaging (MRI)-based parameters with established histomorphological markers of tumor angiogenesis [histological microvessel density (HMVD) and vascular endothelial growth factor expression (VEGF)]; and (b) determine the ultimate value of both approaches to assess functional angiogenic active hotspots as markers of disease outcome in patients with cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, tissue exchange rate constant k21) were calculated from contrast-enhanced dynamic MRI series in 57 patients (mean age, 49 +/- 14 years) with biopsy proven uterine cervical cancer. Both pharmacokinetic parameters were correlated to histomorphologically determined areas of high HMVD and VEGF expression obtained from the operative specimens after radical surgery. In addition, the functional MRI and histomorphological data were used to assess disease outcome. A significant association was found between HMVD and the amplitude A (P < 0.001) and a less pronounced association with k21, (P < 0.05), respectively. No significant associations were found between the pharmacokinetic parameters (A, k21) and VEGF expression. When stratified into high and low median k21 groups, median k21 values >5.4 min(-1) were the only significant (P < 0.05) factors in predicting poor patient survival. None of the histomorphological markers of angiogenesis (HMVD or VEGF expression) showed any predictive power. We have found that: (a) focal hotspots of HMVD are the pathophysiological basis for differences in functional MRI; (b) areas of high microvessel density and microvessel permeability do not necessarily coincide, as demonstrated by the histomorphological and functional MRI findings; (c) the functional angiogenic activity of a tumor may not be sufficiently characterized by a histomorphological approach but rather by a functional MRI-based approach; and (d) functional MRI-based analysis may assess tumor angiogenic activity in terms of disease outcome more comprehensively than the histomorphological approach.     

Neo-angiogenesis in locally advanced squamous cell head and neck cancer correlates with thymidine phosphorylase expression and p53 nuclear oncoprotein accumulation

Thymidine phosphorylase (Th.P) is an angiogenic factor shown to induce endothelial cell migration and proliferation. On the other hand, loss of wild type p53 function leads to down-regulation of thrombospondin-1, an inhibitor of angiogenesis. In this immunohistochemical study we investigated the intratumoural angiogenesis and thymidine phosphorylase (Th.P) expression in paraffin-embedded bioptical material from 104 locally advanced squamous cell head and neck cancers. The nuclear accumulation of mutant p53 protein and the cytoplasmic expression of bcl-2 protein was also assessed. High vascular grade was observed in 56% and high Th.P tumour cell reactivity in 48% of cases. High microvessel score was associated with an increased percentage of cancer cells expressing thymidine phosphorylase (P = 0.001). Increased p53 nuclear accumulation also correlated with high vascular grade (P = 0.001). High histological grade and absence of bcl-2 overexpression were associated with lymph node involvement (P = 0.002 and P = 0.02 respectively). No correlation of clinically detected lymphadenopathy with angiogenesis and p53 was observed. We conclude that intense neo-angiogenesis in locally advanced squamous cell head neck cancer is a frequent event, which is associated with nuclear p53 accumulation and thymidine phosphorylase overexpression.     

Transvaginal color Doppler in early pregnancy: rational and clinical potential

Remarkable hemodynamics changes that occur in the maternal circulation, the continuous growth and development of the feto-placental circulation is now studied by transvaginal Doppler. This seems to give more light in understanding of the early pregnancy pathophysiology. For the first time, it seems that ultrasound might be able to distinguish different forms of gestational trophoblastic disease. Due to its non-invasiveness and relatively simple and easily performed technique, transvaginal color Doppler might be of considerable clinical value. The other important point is that study results are available immediately for clinical judgement. From our study, we can conclude that transvaginal ultrasound with color and pulsed Doppler is potentially valuable diagnostic tool to differentiate forms of the gestational trophoblastic diseases. On the basis of Doppler findings, the complete mole can be reliably distinguish from the invasive mole or choriocarcinoma. The degree of myometrial invasion can be also assessed. This can be an objective foundation for therapeutical approach. There is no doubt that studies of maternal-fetal circulation in early pregnancy may help for better understanding of physiological and pathophysiological hemodynamic changes. Investigation of maternal (main uterine, arcuate, radial and spiral) arteries; placental (umbilical, chorionic arterioles) vessels and fetal (aorta and intracranial circulation) arteries flow patterns may help in order to diagnose abnormal implantation. More studies are necessary in order the Doppler technique to be used for clinical judgment in early pregnancy. Safety aspects should also be considered. However, potentials of these technique are more then obvious.     

Angiogenesis in squamous cell carcinoma in situ and microinvasive carcinoma of the uterine cervix

OBJECTIVE: To evaluate angiogenesis in squamous cell carcinoma in situ (CIS) and microinvasive squamous cell carcinoma of the uterine cervix and to investigate the relations among angiogenesis, stromal inflammation, and depth of invasion. METHODS: Three groups of women were studied: 22 controls who had undergone hysterectomy for benign conditions; 18 with squamous cell CIS of the cervix who underwent cone biopsy, hysterectomy, or both; and 14 with microinvasive squamous cell carcinoma who underwent conization of the cervix and subsequent surgical management according to depth of invasion. All specimens were stained immunohistochemically for factor VIII-related antigen. Areas below the basement membrane with the highest angiogenic density were selected. The degree of stromal inflammatory reaction was assessed. Statistical analyses included Kruskal-Wallis, analyses of variance and covariance, Scheffe and Bonferroni-Dunn post hoc procedures, and Pearson correlation analysis. P < .05 was considered statistically significant. RESULTS: Microvessel counts per high-power field (x 400) of microinvasive squamous cell carcinoma of the cervix differed significantly from those of controls and squamous cell CIS (median 34.5 per high-power field, range 9-76 versus median 17, range 7-47, and median 19, range 8-39, respectively; P < .005). Microvessel counts per high-power field in squamous cell CIS did not differ significantly from those of controls (P = .91). Among patients with microinvasive squamous cell carcinoma of the cervix, no significant correlation was found between microvessel counts per high-power field and the depth of invasion (r = 0.19, P = .51). Stromal inflammatory reaction (graded 0-3) differed significantly among controls, squamous cell CIS, and microinvasive carcinoma (mean 0.40, 0.83, and 1.64, respectively; P < .005). CONCLUSIONS: Microinvasive squamous cell carcinoma of the uterine cervix is angiogenic, but depth of invasion is not associated with increased angiogenicity. Squamous cell CIS is not angiogenic.     

Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma

Intratumoral proteases are known to be involved in not only tumor cell invasion but also a variety of stromal reactions including neovascularization. In this study, we have examined the expression of matrix metalloproteinases (MMPs) by gelatin gel zymography and compared its expression with angiogenesis activities including the expression of several endothelial growth regulators and intratumoral microvessel density (MVD) in human breast cancer tissues. There was a significant correlation between activated MMP-2 expression and vascular endothelial growth factor (VEGF) expression (p=0.045). In addition, the expression of activated MMP-9 expression was significantly correlated with thymidine phosphorylase (TP) expression (p=0.0044). Pro MMP-9 expression tended to correlated with the increment of MVD (p=0.063). MMP-2 and MMP-9 expressions were frequently co-upregulated with endothelial growth regulators in human breast cancer tissues, which underlines the cooperative function of MMPs in neovascularization.     

Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro

A total of 96 women undergoing in-vitro fertilization (IVF) treatment were examined by transvaginal ultrasonography with colour and pulsed Doppler ultrasound on the 22nd day of the menstrual cycle preceding IVF. We assessed endometrial thickness, endometrial morphology, myometrial echogenicity, subendometrial vascularization, the uterine artery pulsatility index, protodiastolic notch and end diastolic blood flow in order to define a uterine score which could be correlated with the pregnancy rate. The overall pregnancy rate was 30.2%, and there was no difference between the pregnant and non-pregnant groups with regard to any of the ultrasonographic and Doppler parameters when examined separately. However, the uterine score was significantly higher in the pregnant group (15.9 +/- 2.81 versus 12.7 +/- 5.3, P = 0.002; t-test). No pregnancy occurred if the score was between 0 and 10. With a score of 11-15 there was a 34.7% chance of pregnancy, and scores >16 had a 42% chance of pregnancy. In conclusion, individual ultrasonographic and Doppler parameters are not of sufficient accuracy to predict uterine receptivity. The uterine score calculated prior to IVF cycles appears to be a useful predictor of implantation.