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Biomedical subjects

P G Knapstein

Publications and source records attributed to P G Knapstein.

At least 19 recordsLinked to original sources
PubMed2000

(A)symptomatic necrotizing arteritis of the female genital tract.

AIMS: The vasculitides represent a heterogenous set of disorders that differ in prognosis and response to therapy. Beside systemic vasculitides, the development of localized forms of arteritis is well known though uncommon and the etiopathogenesis is not yet definitely clear. METHODS: Patients with necrotizing arteritis of the female genital tract proven by histology are studied in a retrospective analysis. RESULTS: Three cases of necrotizing arteritis with histological features of panarteritis nodosa apparently confined to the female genital tract are presented. None of these patients had prior history of systemic vasculitis. The acute necrotizing vasculitis was confined only to the uterine cervix in two patients and involved all the internal genital organs in the third patient. The patients have been observed for up to 4 years without any therapy for these lesions and without any manifestation of systemic vasculitic progression. CONCLUSION: It is to speculate that focal arteritis of the female genital tract is a benign form of panarteritis nodosa or moreover a totally different entity with identical morphogenesis but possibly different pathogenesis. Furthermore it seems to be important to be aware of the specificity of focal arteritis in female genital tract as distinct from the generalized form to prevent unnecessary surgical or chemotherapeutical therapy for this lesion. The benign entity of local arteritis in the female genital tract is discussed in contrast to the severe prognosis of systemic panarteritis nodosa.

Aged↗
PubMed1999

Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer.

Overexpression of the c-erbB-2 (HER-2/neu) oncogene, which encodes a transmembrane receptor tyrosine kinase, has been shown to be associated with poor prognosis in ovarian and breast cancer. Recent studies indicate that c-erbB-2 may also be involved in determining the chemosensitivity of human cancers. In the present study, we examined the role of c-erbB-2 for chemoresistance in ovarian cancer. Overexpression of c-erbB-2 mRNA in tumor tissue was associated with a shorter survival of patients with primary ovarian cancer (P = 0.0001; n = 77) and was an independent prognostic factor in the proportional-hazard model adjusted for International Federation of Gynecologists and Obstetricians stage, residual disease, chemotherapy, and age (P = 0.035). A significant association between expression of c-erbB-2 mRNA and survival was obtained for the subgroup of patients who received a standard chemotherapy with carboplatin or cisplatin and cyclophosphamide (P = 0.0003), whereas only a nonsignificant trend was observed for patients who did not receive a standard chemotherapy (P = 0.124). In addition, the application of a standard chemotherapy improved the survival of patients with relatively low c-erbB-2 expression (P = 0.013) but not of patients with overexpression of c-erbB-2 (P = 0.359). Expression of c-erbB-2 mRNA correlated with expression of topoisomerase IIalpha mRNA determined by a reverse semiquantitative PCR technique (P = 0.009), whereas expression of c-erbB-2 and topoisomerase IIbeta mRNA did not correlate (P = 0.221). To examine the hypothesis that coamplified and/or coregulated topoisomerase IIalpha contributes to the resistance of c-erbB-2-overexpressing carcinomas, we established a chemosensitivity assay using primary cells from an ovarian carcinoma that overexpressed both c-erbB-2 and topoisomerase IIalpha. The combination of carboplatin with nontoxic concentrations of the topoisomerase II inhibitors etoposide or novobiocin enhanced the toxicity of carboplatin. In contrast, the tyrosine kinase inhibitor emodin exhibited no chemosensitizing effect in cells of this individual carcinoma. In conclusion, overexpression of c-erbB-2 was associated with poor prognosis and poor response to chemotherapy. The data suggest that topoisomerase IIlalpha, which correlates with c-erbB-2 expression, contributes to the resistance of c-erbB-2-overexpressing carcinomas.

Antigens, Neoplasm↗
PubMed1999

Ovarian endometrioid-like yolk sac tumor treated by surgery alone, with recurrence at 12 years.

We describe the case of a stage Ia endometrioid-like yolk sac tumor (YST) of the ovary, which was originally misdiagnosed as a malignant struma ovarii and not treated with adjuvant chemotherapy. After 12 years, a contralateral dermoid cyst was excised along with a small omental nodule of partially necrotic and calcified endometrioid-like YST. No tumor was detected in several other biopsy specimens, and a peritoneal lavage was negative for tumor cells. Since there was no evidence of remaining tumor and the serum alpha-fetoprotein (AFP) level was normal after the second operation, the patient was followed. Serial serum AFP levels remained normal for 4 months. At a second-look laparotomy after 4 months, a small tumor nodule was removed from the cul-de-sac. Postoperatively, the patient received three cycles of BEP chemotherapy. The long disease-free interval after the first operation in spite of the presence of occult spread to the omentum and to the pouch of Douglas in this case indicates that some endometrioid-like YSTs may have an indolent course. The present case underscores the importance of careful surgical staging and of long-term follow-up in cases of primitive germ cell tumors of the ovary.

Adult↗
PubMed1999

Expression of tenascin in human cervical cancer--association of tenascin expression with clinicopathological parameters.

OBJECTIVE: Tenascin is an extracellular matrix glycoprotein, relevant for embryonal and fetal development, which is reexpressed in the stroma of benign and malignant tumors. Little is known about the molecular interaction of tenascin during neoplastic transformation and tumor progression in cervical cancer. METHOD: We studied the expression of tenascin in normal tissue of the cervix uteri, cervical carcinoma in situ, and invasive cervical carcinoma in paraffin sections by immunohistochemistry using a monoclonal antibody. Tenascin immunoreactivity was compared with various prognostic parameters. RESULTS: In normal cervical tissue (n = 5) and in cervical carcinoma in situ (n = 10) only vessel walls showed a weak tenascin cross-reactivity, whereas tenascin was not expressed in the epithelial layer or the underlying connective tissue. In invasive cervical carcinoma (n = 89) tenascin expression was markedly increased. In 84% (n = 75) of the cases examined a strong tenascin immunoreactivity was noted around and within the tumor cell nests. Sixteen percent (n = 14) of infiltrating cervical carcinomas showed no tenascin immunoreactivity. A definite correlation was found between weak or no tenascin expression and slight desmoplastic mesenchymal reactivity (n = 42/91%, P < 0.001), lymphatic space invasion (n = 54/81%, P < 0.001), and lymph node metastases (n = 30/77%, P < 0.05). Tenascin-positive patients had a significantly better prognosis than tenascin-negative patients (mean survival time of 56.5 +/- 4.1 months versus 31.9 +/- 5.6 months, P < 0.05). CONCLUSION: Based on these findings we discuss that the appearance of tenascin is an indicator of an adequate biological defense in cervical cancer patients. The tenascin staining may therefore be useful for detecting a subgroup of invasive cancer patients missing tenascin reactivity with alterations of stromal defense and a poorer prognosis.

Carcinoma in Situ↗
PubMed1999

Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival.

Since detailed knowledge regarding the pathophysiological properties which in turn are responsible for differences in contrast enhancement--remain fairly undetermined, it was the aim of this study (i) to examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis (microvessel density [MVD]; vascular endothelial growth factor [VEGF]); and (ii) to determine the ultimate value of a histomorphological and a dynamic MRI approach by correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, exchange rate constant k21) and standard parameters (maximum signal intensity (SI)-increase [SI-I] over baseline and steepest SI-upslope per second [SI-U/s]) were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with similar sized and positioned regions-of-interest (ROIs) on the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and amplitude A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between the VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05, 0.001, respectively) worse disease outcome than tumors with low k2, and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD, VEGF) had any significant power to predict patient survival. It is concluded that (1) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF-expression; (2) a functional, dynamic MRI approach (both standard and a pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis; and [3] compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.

Adult↗
PubMed1999

[Value of clinically established MRI procedures concerning the pretherapeutic evaluation of maximal tumor diameter in primary or recurrent cervix cancer in relation to palpation findings and histopathologic whole mount specimens].

OBJECTIVE: The maximal tumor diameter of cervical cancer is one of the most important prognosis factors concerning patients' survival. The purpose of this study was to investigate the efficiency of different MRI-procedures in relation to clinical palpation concerning pretherapeutic tumor diameter assessment. MATERIAL AND METHODS: Thirty-one patients with biopsy proven primary cervical cancer and its recurrence (n = 10), respectively, underwent dynamic and conventional MRI before further treatment. The results of maximal tumor diameters were compared to palpatory findings and then correlated to the whole mount specimen as gold standard. RESULTS: The contrast-enhanced dynamic and T2-weighted MRI allows a significantly better (p < 0.05) assessment of maximal tumor diameter of cervical cancer than the conventional T1-weighted MRI. The T2-weighted MRI showed the highest correlation (r = 0.83) in respect to the whole mount specimen up to FIGO-IIB disease. The contrast-enhanced dynamic MRI and the palpation were characterized by the highest correlation coefficients of r = 0.77, r = 0.70 respectively, in advanced cervical cancer > FIGO-IIB disease. CONCLUSIONS: The MRI procedures offer no evident advantage in relation to clinical palpation to determine the maximal tumor diameter of cervical cancer or its recurrency and seems not to be indicated generally.

Adult↗
PubMed1999

[Anxiety and coping behavior before and after radical gynecological surgery].

Pretreatment phase-interactions between patient, family and medical staff around the time of diagnosis may have profound and long-term effects on quality of life. These interactions do not only influence the ability of the patient to come to terms with the diagnosis, but often set the tone for all future dealings with medical community. The imperatives for the medical staff in this process are to provide both: information and hope. In this context, anxiety and defense mechanisms--as protection of ego against anxiety--are psychoanalytic based constructs. The investigation of the interference between these constructs and information reflects the extraordinary background for an effective and continuing communication. These considerations require the care team to individualize their approach to each patient.

Adaptation, Psychological↗
PubMed1998

Uterine cervical carcinoma: comparison of standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as for therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this study to: (a) examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)]; and (b) determine the ultimate value of a histomorphological and a dynamic MRI approach by the correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) and standard parameters [the maximum signal intensity increase over baseline (SI-I) and the steepest signal intensity-upslope per second (SI-U/s)] were calculated from a contrast-enhanced dynamic MRI series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD and VEGF) were compared to MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05 and 0.001, respectively) worse disease outcome than did tumors with low k21 and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD and VEGF) had any significant power to predict patient survival. It is concluded that in patients with uterine cervical cancer: (a) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF expression; (b) a functional, dynamic MRI approach (both standard and pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than are the current histomorphological-based markers of tumor angiogenesis; and (c) compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.

Contrast Media↗
PubMed1998

Resistance factors in colon cancer tissue and the adjacent normal colon tissue: glutathione S-transferases alpha and pi, glutathione and aldehyde dehydrogenase.

Glutathione S-transferases (GST) alpha and pi, glutathione (GSH) and aldehyde dehydrogenase (ADH) were determined in colorectal cancer tissue specimens and in the adjacent normal colon tissue. The median contents in normal and cancer tissue were 8.1 (2.3-30.3) (5-95% quantiles) and 15.1 (5.3-50.3) microg/mg protein for GST pi (P = 0.035), 0.0 (0.0-1.4) and 0.4 (0.0-3.5) microg/mg protein for GST alpha (P = 0.019), 7.3 (1.3-22.7) and 5.6 (2.3-26.0) microg/mg protein for GSH (P = 0.171) and 30.8 (13.0-42.0) and 23.2 (9.0-32.9) microg/mg protein for ADH (P = 0.0017), respectively. Thus, the mean GST alpha and pi both significantly increased in colon cancer compared to the adjacent normal tissue, which underlines their importance as possible resistance factors. A highly significant correlation was obtained between the GSH content in colon cancer and normal tissue (P = 0.0017). Thus, the constitutive GSH expression seems to be maintained during tumor development. A similar correlation was obtained for ADH (P = 0.0075), but the median ADH was lower in cancer tissue compared to the adjacent normal tissue (P = 0.0017). Contrary to GSH and ADH, GST pi did not correlate between normal and colon cancer tissue. Whereas GSH and ADH correlated in normal colon tissue (P = 0.014), no significant correlation for GSH and ADH was observed in colon cancer tissue (P = 0.109). In conclusion, significant correlations between colon cancer and normal tissue were obtained, suggesting that the expression levels of these resistance factors are maintained during carcinogenesis in most patients.

Aldehyde Dehydrogenase↗
PubMed1998

[Angiogenesis of cervix carcinoma. Contrast enhanced dynamic MRI, histologic quantification of capillary density and lymphatic system infiltration].

PURPOSE: It was the aim of this project to examine (i) the relationships between contrast-enhanced dynamic MR imaging derived characteristics and histologic microvessel density counts--a recognized surrogate of tumor angiogenesis--from tumors in patients with primary or recurrent cancer of the uterine cervix, and (ii) to correlate these parameters with lymphatic involvement (i.e. lymphatic channels) to assess tumor biological aggressiveness in terms of lymphatic spread. MATERIAL AND METHODS: Pharmacokinetic MR imaging parameters (amplitude A, exchange rate constant k21) were derived from contrast-enhanced dynamic MR imaging in thirty-three patients with biopsy proven cancer of the uterine cervix. The pharmacokinetic MR imaging characteristics were correlated to histologic capillary density counts obtained from whole mount specimen. In addition, these data were correlated to the angiogenic activity as a marker for lymphatic system involvement. RESULTS: Pharmacokinetic MR imaging derived parameters (A, k21) showed a weak but significant (p < 0.05) correlation with microvessel density counts. Lymphatic involvement was more comprehensively assessed by the pharmacokinetic parameter k21 compared with histologic microvessel density, resulting in a significantly (p < 0.05) higher overall accuracy (85% vs. 64%), sensitivity (83% vs. 54%), and comparable specificity (89% vs. 89%), respectively. CONCLUSION: Our first results show that the signal-time curves measured by contrast-enhanced MR imaging are only in part influenced by microvessel density. In addition, MR imaging derived characteristics may assess tumor biological aggressiveness in terms of lymphatic spread (i.e. lymphatic channels) more comprehensively than histologic microvessel density in patients with primary or recurrent cancer of the uterine cervix.

Adult↗
PubMed1998

[MRI imaging of the uterine arterial blood flow in normal and malignant uterine tissue by means of 2d-multiphase tagging technic].

PURPOSE: The aim of this pilot study was to evaluate a 2D-STAR technique as a non contrast-enhanced approach to demonstrate the uterine artery and its branches and to assess the cervical uterine blood flow in healthy volunteers and in patients with advanced uterine cervical carcinoma. MATERIALS AND METHODS: Seven healthy volunteers (mean age, 29 years) and twenty-two patients (mean age, 52 years) with advanced cancer of the uterine cervix (FIGO IIB-IVA) were prospectively examined by 2D-STAR imaging at different inversion delay times (300 ms-1900 ms) which showed the passage of a blood bolus through normal and malignant tissue of the uterine cervix. RESULTS: The uterine artery was well visualized with short inversion delay times of 300 ms to 500 ms. It was characterized as single or multiple helical loops before dividing into its intracervical branches. The intracervical branching was observed at inversion delay times of 500 ms-700 ms. With longer inversion delay times arterial signal enhancement disappeared and cervical tissue enhancement was noted. Enhancement of benign tissue was observed at inversion delay times of 1100 ms-1700 ms, and in malignant tissue at shorter inversion delay times of 900 ms-1300 ms. The maximum of this diffuse signal enhancement of benign tissue was seen at inversion delay times of 1500 ms (1100 ms-1700 ms), in malignant tissue at significantly (P < 0.05) shorter inversion delay times of 1100 ms (900 ms to 1300). CONCLUSION: Our preliminary results show that the vascular supply and blood flow of the normal uterine cervix and of advanced cervical cancer can be assessed by non contrast-enhanced 2D STAR imaging and that malignant cervical tissue is earlier and stronger perfused than normal cervical tissue.

Adult↗
PubMed1998

[Integration of functional and morphologic MRI data for preoperative 3D visualization of tumors. Example: cervical carcinoma].

PURPOSE: The goal of this exemplary study was to integrate morphological and functional MRI to establish computer-based, pre-operative therapy planning for tumors, instancing cervical carcinoma. METHODS: For morphological representation T1-weighted, filtered 3D sequences were investigated within a hierarchical segmentation approach. Using a method for image registration, segmented structures were combined and overlaid with functional information of contrast medium-enhanced, dynamic MRI. After assigning colour attributes to the segmented structures, they were presented using a method for direct volume visualisation. RESULTS: Segmentation of organs and vessels as well as tissue differentiation yielded a morphological visualisation of anatomical structures that were overlaid with pharmacokinetic parameters derived from dynamic MRI, subsequently. Thereby, three-dimensional, arbitrary views on the functional data were displayed. CONCLUSIONS: Image analysis and visualisation of the acquired MR data establishes both a morphologic and functional evaluation of suspect lesions and adjacent organs. By integrating morphologic and functional MRI additional information can be gathered that possibly impinge on preoperative planning.

Data Interpretation, Statistical↗
PubMed1998

Magnetically labeled water perfusion imaging of the uterine arteries and of normal and malignant cervical tissue: initial experiences.

PURPOSE: The aim of this pilot study was to evaluate a magnetically labeled water perfusion imaging technique as a non-contrast-enhanced approach to demonstrate the uterine artery, its branches, and to assess the cervical uterine blood flow in healthy volunteers and in patients with advanced uterine cervical carcinoma (FIGO IIB-IVA). METHODS AND MATERIALS: Seven healthy volunteers (mean age, 29 years) and twenty-two patients (mean age, 52 years) with advanced cancer of the uterine cervix (FIGO IIB-IVA) were prospectively examined by magnetically labeled water perfusion imaging at different inversion delay times (300-900 ms). The magnetic resonance imaging (MRI) findings of all patients were matched to the findings of contrast-enhanced dynamic MRI and multiple biopsies (n = 5) and/or surgical whole mount specimens (n = 17), which were available in all patients. RESULTS: The uterine artery was well visualized with short inversion delay times of 300-500 ms. It was characterized as single or multiple helical loops before dividing into its intracervical branches. The intracervical branching was observed at inversion delay times of 500-700 ms. With longer inversion delay times, arterial signal enhancement disappeared and cervical tissue enhancement was noted. Enhancement of benign tissue was observed at inversion delay times of 1100-1700 ms and in malignant tissue at shorter inversion delay times of 900-1300 ms. The maximum of this diffuse signal enhancement of benign tissue was seen at inversion delay times of 1500 ms (1100-1700 ms) in malignant tissue at significantly (p < 0.5) shorter inversion delay times of 1100 ms (900-1300 ms). CONCLUSION: Our preliminary results show that the vascular supply and blood flow of the normal uterine cervix and of advanced cervical cancer can be assessed by magnetically labeled water perfusion imaging and that malignant cervical tissue is earlier and stronger perfused than normal cervical tissue.

Adult↗
PubMed1998

[Detection of angiogenesis-dependent parameters by functional MRI: correlation with histomorphology and evaluation of clinical relevance as prognostic factor using cervix carcinoma as an example].

PURPOSE: Purpose of this study is to compare functional MRI parameters with histomorphological markers of tumor microvessel density (MVD) and permeability (vascular endothelial growth factor) and to determine the ultimate value of both approaches by correlation with disease outcome in patients with primary cancer of the uterine cervix. METHOD: Pharmacokinetic parameters were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the operative whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using logrank statistics. RESULTS: Significant (p < 0.05-0.01) associations were found between MVD and dynamic MRI parameters. No significant relationships were observed between VEGF expression and dynamic MRI parameters. Disease outcome was better assessed with dynamic MRI parameters than with the histomorphological approach. CONCLUSIONS: It is concluded that 1) the pathophysiological basis for the amplitude A in dynamic MRI is MVD but not VEGF expression; and 2) a functional, dynamic MRI approach may be more suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis.

Adult↗
PubMed1998

C-myc mRNA expression in epithelial ovarian carcinomas in relation to estrogen receptor status, metastatic spread, survival time, FIGO stage, and histologic grade and type.

Recently, it has been suggested that c-myc expression might correlate with estrogen receptor (ER) status and metastatic spread in ovarian cancer. In this study, expression of c-myc mRNA in 90 epithelial ovarian carcinomas was determined using the S1 nuclease protection assay. Expression of c-myc mRNA was detectable in 27 of 90 tumors. There was no significant association between c-myc mRNA expression and metastatic spread, survival time, FIGO stage, or histologic grade and type. C-myc mRNA was expressed in 45% of ER-positive tumors but only 24% of ER-negative tumors (p = 0.094; Fisher's exact test). Similarly, 44% of progesterone receptor (PR)-positive and 23% of PR-negative tumors expressed c-myc mRNA (p = 0.098). However, the association between c-myc mRNA expression and ER and PR status was not statistically significant. The ratio of mean expression of c-myc mRNA in patients with FIGO stages III/IV compared with patients with FIGO stages I/II was 2.1:1, an insignificant difference (p = 0.57, Wilcoxon rank sum test). In conclusion, c-myc was not significantly associated with the clinical parameters investigated in this study.

Carcinoma↗
PubMed1998

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.

Adult↗