Number Of Intratumoral Vessels Research Articles

Peliminary exploration on the differential diagnosis between meningioma and schwannoma using contrast-enhanced T1WI flow-sensitive black-blood sequence.

Contrast-enhanced T1WI flow-sensitive black-blood (CE-T1WI FSBB) is a newly developed sequence which had not been widely used for differential diagnosis of brain tumors. To quantify the pre-operative imaging features of intratumoral microbleeds and intratumoral vessels using CE-T1WI FSBB scan and study the differences in biological behavior of meningiomas and schwannomas underlying the imaging features. Seventy-three cases of meningiomas and 24 cases of schwannomas confirmed by postoperative pathology were included. Two neuroradiologists independently counted intratumoral vessels and intratumoral microbleeds based on CE-T1WI FSBB images. The vessel density index (VDI) and microbleed density index (MDI) were the number of intratumoral vessels and the number of intratumoral microbleeds divided by the tumor volume, respectively. The consistency test of intratumoral vessel count and intratumoral microbleed count based on CE-T1WI FSBB were summarized using 2-way random intraclass correlation coefficients (ICC). Mann-Whitney U-test and chi-square test were used to determine significant differences between meningiomas and schwannomas, and fibrous meningiomas and epithelial meningiomas. P<0.05 was considered statistically significant. The ICC of intratumoral vessels count and intratumoral microbleeds count were 0.89 and 0.99, respectively. There were significant differences in the number of intratumoral microbleeds (P<0.01) and MDI values (P<0.01) between meningiomas and schwannomas. There were no differences in the number of intratumoral vessels (P=0.64), VDI (P=0.17), or tumor volume (P=0.33). There were also differences in the number of intratumoral microbleeds (P<0.01), the MDI value (P<0.01), and the sex of patients (P<0.05) between fibrous meningiomas and epithelial meningiomas. CE-T1WI FSBB can be a new technique for differentiating schwannomas from meningiomas, and even different types of meningiomas. Schwannomas have a higher incidence of intratumoral hemorrhage, more intratumoral microbleeds, and higher MDI values than meningiomas, which provides a new basis for preoperative differential diagnosis and treatment decisions.

Preoperative Assessment of Blood Vessels and Intratumoral Microbleeds in Brain Tumors Based on a 3D Contrast-Enhanced T1 -Weighted Flow-Sensitive Black-Blood Sequence.

Three-dimensional (3D) contrast-enhanced T1 -weighted flow-sensitive black-blood (CE-T1 WI FSBB) is a newly developed black blood sequence by adding motion probing gradient pulses to gradient echo (GRE) sequences, which has important value for the preoperative assessment of tumor brain blood supply vessels and intratumoral microbleeds. To compare 3D CE-T1 WI FSBB and 3D contrast-enhanced fast spin echo (FSE) sequence for T1 WI for preoperative assessment of blood vessels and microbleeds in brain tumors and to investigate the correlation between visible vessels and microbleeds. Prospective. One hundred and seventy-five patients with brain tumors, 65 were male, 110 were female. Including histologically confirmed 73 meningiomas, 23 schwannomas, 20 gliomas, 7 hemangioblastomas, 5 metastases, 2 lymphomas, 2 hemangiopericytomas, 2 germ cell tumors, 1 craniopharyngioma, and 1 cholesteatoma. A 3-T, CE-T1 WI FSBB, GRE; 3-T, CE-T1 WI, FSE. Three neuroradiologists counted the number of intratumoral vessels on CE-T1 WI and CE-T1 WI FSBB images separately, and they counted the number of intratumoral microbleeds on CE-T1 WI FSBB images. Brain tumors were classified into grade I, grade II, and grade IV according to the World Health Organization (WHO) grading. Differences in the ability of CE-T1 WI FSBB and CE-T1 WI to display intratumoral vessels were compared. The mean counts of three observers were used to study the correlation between vessels and microbleeds. Two-way random intraclass correlation coeficient (ICC) was used for inter-reader agreement regarding intratumoral vessel and microbleed counts, and the linear regression analysis (with F-test) was used to study the correlation between intratumoral vessels and microbleeds based on CE-T1 WI FSBB (α=0.05). Inter-reader agreements for intratumoral vessel count on CE-T1 WI (ICC=0.93) and CE-T1 WI FSBB (ICC=0.92), and the agreement for intratumoral microbleed count on CE-T1 WI FSBB (ICC=0.99) were excellent. There were statistically significant differences in intratumoral vessel counts between CE-T1 WI and CE-T1 WI FSBB using Mann-Whitney U -test: image readers could identify more intratumoral vessels on CE-T1 WI FSBB images, particularly for meningiomas, schwannomas, gliomas, and WHO grade I tumors. The number of intratumoral vessels had a significant positive effect on the number of intratumoral microbleeds (microbleeds=5.024 + 1.665 × vessels; F=11.51). More intratumoral vessels could potentially be identified using a 3D CE-T1 WI FSBB sequence compared to a CE-T1 WI sequence, and the number of intratumoral vessels showed a positive linear relationship with the number of intratumoral microbleeds, which might suggest that brain tumors with rich blood supply were more prone to intratumoral microbleeds. 2 TECHNICAL EFFICACY: Stage 3.

T19: The immune and vascular components of microenvironment in prognosis of the endometrioid endometrial adenocarcinoma

Background Endometrioid endometrial adenocarcimoma is the most frequent gynecologic malignancy in the western world. It is well known that inflammation plays a key role in the initiation and development of cancer as well as promotes both specific and innate immune response. There is no information on the status of the local anti-tumor cellular immunity in endometrioid adenocarcinoma of the corpus uteri microenvironment in the Russian and English language medical scientific literature. Various studies have shown that high intratumor microvessel density in endometrial cancer is associated with advanced stage, increased risk of recurrent disease and with poor prognosis. Vascular endothelial growth factor (VEGF) is a glycoprotein with potent mitogenic activity. It has been demonstrated to be a key component in the promotion of angiogenesis. Materials and methods There were singlet 24 cases of endometrioid adenocarcinoma with retrospectively known good (survival) and poor (death) outcomes. All cases were immunohistochemically stained for CD3, CD20, CD57, CD68, S100, CD34 and VEGF, expression of was evaluated by IHC-profiler. The number and the area of vessels was count in “hot spot” zones and calculated per 1 mm. For compare of the characteristics of signs was used comparison of two independent samples – U-Mann–Whitney test. The level of statistical significance was accepted by p Results T-lymphocytes cells were situated predominantly in desmoplastic stroma of the tumor. CD3 expression was significant higher in the group of good outcome (p = 0.00042), B-lymphocytes cells were predominantly in epithelial component of tumor. CD20 was expressed in endometriod adenocarcinoma with good and poor outcome without statistically significant difference (p = 0.976). NK-lymphocytes were predominantly in peritumoral stroma. CD57 expression was statistically significant higher in the group of good outcome (p = 0.000307). Tumor infiltrating macrophages can were frequent in tumor stroma than in tumor islets. CD68 expression cells number was higher in the group with good outcome (p = 0.000219). Dendric cells were predominantly in epithelial component of tumor. S100+ cells number did not have any difference (p = 0.105). Inside the tumor stroma, among pseudo-glands or solid beaches there was a positive reaction for anti-CD34 of numerous microvessels together with groups of endothelial cells (“hot spot”). The number of intratumoral vessels in patients with poor outcome was 141.9 ± 24.7 vessels/mm2, in good outcome patients – 93.8 ± 28.7 vessels/mm2. The number of the intratumoral vessels in this groups was with significant statistical different (p = 0.0014). The area of intratumoral vessels in good outcome cases was 2799.7 ± 535.7 μm2, poor outcome cases – 5455,2 ± 448,8 μm2. It was significant statistical different (p = 0.000014). VEGF was expressed in the cytoplasm of normal endometrial cells, neoplastic ones, endothelial cells and stroma. VEGF represents a mitogen for endothelial cells that induces the formation of lumen’s vessels and also increases vascular permeability and protein extravasation. Expression of VEGF by cancer cells had significant statistical difference in this groups of patients (p = 0.0411). Conclusion There was a significant reduction in T, NK-cells and macrophages from patients with poor outcome indicates the development of local immune deficiency that could certainly plays an important role in tumor progression endometrioid carcinoma. Our study demonstrates that the number and the area of vessels, as part of angiogenesis, represent an important prognostic factor in outcome of endometrioid endometrial adenocarcinoma. VEGF expression also is an angiogenic factor which plays a great role in the prognosis of this tumor.

Neue bildgebende Strategien zum Monitoring molekularer Pharmakotherapien bei GIST

Prognosis and clinical management of patients with gastrointestinal stromal tumors (GIST) has changed significantly with the introduction of new molecular-targeted drugs such as imatinib. This development is accompanied by a need to re-evaluate the established imaging criteria used to assess treatment response. The frequently used response evaluation criteria in solid tumors (RECIST) are mainly based on one-dimensional tumor size and do not take into account functional changes in responding GISTs such as a decrease in CT density or in the number of intratumoral vessels. Positron emission tomography (PET) has been found to be highly sensitive in detecting early response and to have a predictive value in the long term response to imatinib treatment. Monitoring the course of the disease by PET is limited due to scanner availability and economic constraints. Modified CT response criteria using a combination of tumor density and tumor size are especially promising in early response assessment and have a good prognostic value. Further optimization of existing response criteria and evaluation of new candidate markers of treatment response, such as quantitative perfusion will be the key for optimized monitoring of targeted therapies in GIST.

The Lessons of GIST—PET and PET/CT: A New Paradigm for Imaging

Traditional anatomic tumor response criteria are based on uni- or bidimensional changes in tumor size, and do not take into account changes in tumor metabolism, tumor density, or decrease in the number of intratumoral vessels. These changes are, however, all indicative of response to imatinib therapy in patients with gastrointestinal stromal tumor (GIST). In these patients, metabolic responses seen on positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (18FDG) have been shown to be closely related to clinical benefit. Furthermore, these metabolic changes precede by weeks or months significant decrease in tumor size on computed tomography (CT). Conversely, lack of metabolic response on FDG-PET indicates primary resistance to the drug and may help identify patients who would benefit from another therapy, while re-emergence of metabolic activity within tumor sites following a period of therapeutic response indicates secondary resistance to the drug. Newly proposed CT criteria using either no growth in tumor size or a combination of tumor density and size criteria have shown a close correlation with the predictive value results of FDG-PET. Thus, the integration of FDG-PET and CT, as in the combined hybrid PET/CT scanners now available, will not only optimize the evaluation of patients with GIST treated with molecularly targeted drugs, but may ultimately help shorten clinical trials, and accelerate drug development in this disease and other cancers as well.

Response Evaluation of Gastrointestinal Stromal Tumors

Clinical management of patients with gastrointestinal stromal tumors (GISTs) has dramatically changed with the introduction of novel therapeutics, such as imatinib mesylate. This has created a need to re-evaluate the existing criteria used to assess treatment response. The current Response Evaluation Criteria in Solid Tumors are based on unidimensional tumor size, and do not take into account changes in responding GISTs such as a decrease in tumor density and decrease in the number of intratumoral vessels with computed tomography (CT). Positron emission tomography (PET) has been found to be highly sensitive in detecting early response, and to be useful in predicting long-term response to imatinib in patients with metastatic GIST; however, widespread use of PET is limited because of a lack of scanner availability and cost constraints. Modified CT criteria using a combination of tumor density and tumor size are promising in early response evaluation, and have excellent prognostic value. Identifying appropriate treatment response criteria is essential to optimize treatment for patients with GIST.

Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in murine lewis lung carcinoma and human Calu-6 non-small-cell lung carcinoma xenografts.

In cell culture, the compound 317615.2HCl, a potent inhibitor of VEGF-stimulated HUVEC proliferation, was not very effective against Calu-6 non-small-cell lung carcinoma cells (IC50 26 microM). Exposure to combinations of paclitaxel or carboplatin and 317615.2HCl with Calu-6 cells in culture resulted in cell survival that reflected less-than-additivity to additivity of the two agents. Administration of 317615.2HCl orally twice daily to nude mice bearing subcutaneous Calu-6 tumors resulted in a decreased number of intratumoral vessels as determined by CD31 and CD105 staining to 50% of the number in control tumors. 317615.2HCl showed antitumor activity against the Lewis lung carcinoma and increased the tumor growth delay produced by paclitaxel by 5-fold, that produced by gemcitabine by 2-fold and that produced by carboplatin by 1.7-fold. There was a decrease in the number of lung metastases in the Lewis lung carcinoma that paralleled the increased response of the primary tumor with each treatment combination. Administration of 317615.2HCl also increased the tumor growth delay produced by fractionated radiation therapy in the Lewis lung tumor. Treatment with 317615.2HCl was an effective therapy in the Calu-6 non-small-cell lung carcinoma xenograft when the compound was administered early (days 4-18) or later (days 14-30). Combination treatment regimens in which 317615.2HCl was administered along with or sequentially with paclitaxel or carboplatin were much more effective than the chemotherapeutic agents administered alone. 317615.2HCl is in early clinical testing.

VASCULARIZATION OF MALIGNANT AND BENIGN SKIN TUMOURS MEASURED BY d-GALACTOSE-BASED SIGNAL-ENHANCED COLOUR DOPPLER SONOGRAPHY

Evaluation of colour Doppler criteria to differentiate between malignant and benign skin tumours on the basis of the degree of vascularization. The B-mode sonomorphology and the degree of vascularization in colour Doppler of 81 clinically potentially malignant tumours of cutaneous and subcutaneous structures were analyzed and quantified by number of intratumoral vessels per sonographic slice and percentage vessel area. Of all criteria employed, counting the intratumoral vessels visible on one ultrasound slice after application of a signal-enhancing agent led to highest sensitivity (94%) of all used criteria but the specificity was poor (64%). The highest specificity (88%) and greatest diagnostic accuracy (86%) discriminating benign and malignant lesions were found using the criterion "percentage vessel area >5.0%" after all inflamed lesions had been excluded on the basis of clinical criteria. Plain colour Doppler increased the specificity up to 97%, although the sensitivity decreased simultaneously to max. 75%. Analysis of the B-mode morphology and spectral Doppler parameter of intratumoral vessels did not contribute to the differential diagnosis. Signal-enhanced colour Doppler sonography is a valuable tool in the pretherapeutic assessment of cutaneous lesions. This method may be relevant for therapy and prognosis.

Vascularization of malignant and benign skin tumours measured by D-galactose-based signal-enhanced colour Doppler sonography.

Evaluation of colour Doppler criteria to differentiate between malignant and benign skin tumours on the basis of the degree of vascularization. The B-mode sonomorphology and the degree of vascularization in colour Doppler of 81 clinically potentially malignant tumours of cutaneous and subcutaneous structures were analyzed and quantified by number of intratumoral vessels per sonographic slice and percentage vessel area. Of all criteria employed, counting the intratumoral vessels visible on one ultrasound slice after application of a signal-enhancing agent led to highest sensitivity (94%) of all used criteria but the specificity was poor (64%). The highest specificity (88%) and greatest diagnostic accuracy (86%) discriminating benign and malignant lesions were found using the criterion "percentage vessel area >5.0%" after all inflamed lesions had been excluded on the basis of clinical criteria. Plain colour Doppler increased the specificity up to 97%, although the sensitivity decreased simultaneously to max. 75%. Analysis of the B-mode morphology and spectral Doppler parameter of intratumoral vessels did not contribute to the differential diagnosis. Signal-enhanced colour Doppler sonography is a valuable tool in the pretherapeutic assessment of cutaneous lesions. This method may be relevant for therapy and prognosis.

Increased vascularization in myeloma

Abstract: Several studies have shown that the number of intratumoral vessels can predict the aggressiveness of a solid cancer, development of metastases and patient survival. Does angiogenesis play an important role in myeloma?The aim of our study was to quantify bone marrow vascularity in various stages of proliferative plasma cell disorders (monoclonal gammopathies of undetermined significance (MGUS), stage I multiple myeloma (MM), stage III MM and Waldenström's macroglobulinemia (WM)) and to compare it with that of patients with osteoporosis.The study included 15 MGUS patients, 15 patients with stage I MM, 15 patients with symptomatic stage III MM, 7 patients with WM, 10 patients with osteoporosis, and 10 patients with reactive bone marrow (RBM), matched for sex and age. After iliac crest biopsy, the various vessels (arterioles, capillaries and sinusoids) were labeled with monoclonal antibodies CD34 and counted, and a histomorphometric study was done. The number of arterioles and arterial capillaries was significantly increased in MGUS and myeloma compared with osteoporosis. The number of arterioles and arterial capillaries increased moderately according to the stage of gravity of myeloma. The number of arterioles is negatively correlated with the trabecular bone volume and positively correlated with the eroded surfaces.

Thallium Chloride 201Tl Combined with Single Photon Emission Computed Tomography (SPECT) in the Evaluation of Vestibular Schwannoma Growth

Thallium chloride 201Tl combined with SPECT was performed in a series of 29 patients with neuroradiological evidence of vestibular schwannoma (VS). The relative tumor uptake (U) and relative tumor concentration (C) of the radiotracer 201 Tl was determined, and the cerebellum served as a reference. The relative tracer concentration and uptake were correlated to tumor volume determined by gadolinium DTPA enhanced MR, to prediagnostic duration of symptoms, to tumor vascularity expressed by the average number of intratumoral vessels using the endothelial marker CD31, and to the proliferative activity in the tumors expressed by positive staining with the monoclonal antibody MIB-1 for Ki-67. A positive 201Tl enhancement was detected in 17 tumors (n = 17). Tumors U and C were statistically unrelated to tumor volume (p = 0.236 and p =0.439). SPECT demonstrated all tumors >0.8 cm3 but it had its limitation as a diagnostic modality of small intracanalicular tumors, when compared with gadolinium DTPA enhanced MR. Relating U and C in all tumors (n = 29) and the prospectively registered data on the prediagnostic duration of symptoms, a statistical significance was found (p =0.012 and p =0.015). No statistically significant correlation was observed between U and C and the proliferative activity of the tumors expressed by positive staining with the monoclonal antibody MIB-1 for Ki-67 (p = 0.063 and p = 0.086). A statistically significant correlation was noted between C and U in the operated group (n = 12) and tumor vascularity expressed by the average number of the intratumoral vessels (p = 0.003 and p = 0.014). SPECT was found to be superior to MR in determining VS growth potentials as it expresses tumor vascularity, which is essential for tumor growth. It seems that we now have an in vivo functional radiological modality capable of providing data on VS vascularity and determination of growth potential in the individual tumor. A high radioactive tracer uptake in the tumor corresponded to high tumor vascularity, indicating a high growth rate and vice versa.

Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.