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.

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.

Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as 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 project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.

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.

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.

Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix.

Experimental evidence suggests that the hypoxic fraction in a solid tumor may increase its malignant potential and reduce its sensitivity towards non-surgical treatment modalities (e.g. standard irradiation, certain anticancer agents). However, the clinical importance of tumor hypoxia remains uncertain since valid methods for the routine measurement of intratumoral O2-tensions in patients have so far been lacking. A clinically applicable standardized procedure has been established which enables the determination of intratumoral oxygen tensions in advanced cervical cancers by use of a computerized polarographic needle electrode histography system. Tumor oxygenation as measured by this method represents a novel tumor feature which can be individually determined for each tumor and which is independent from other known oncological parameters. The results of an interim analysis of an open prospective clinical trial to evaluate the prognostic significance of tumor oxygenation based on the survival data of the first 31 patients are presented. Fifteen patients have been treated by primary radiation, 11 patients received multimodality therapy including irradiation. After a median follow-up of 19 months (range 5-31 months), Kaplan-Meier-life table analysis showed significantly lower survival and recurrence-free survival for patients with a median pO2 of < or = 10 mmHg compared to those with better oxygenated tumors (median pO2 > 10 mmHg). The Cox proportional hazards model revealed that the median pO2 and the clinical stage according to the FIGO are independent, highly significant predictors of survival and recurrence-free survival. We conclude from these preliminary results that tumor oxygenation as determined with this standardized procedure appears to be a new independent prognostic factor influencing survival in advanced cancer of the uterine cervix.

Effects of interferon gamma on the proliferation and modulation of cell-surface structures of human ovarian carcinoma cell lines.

Platinum-containing regimens are very effective in the primary treatment of ovarian cancer. However, upon subsequent treatment most tumors develop multidrug resistance. The clinical application of biological response modifiers like interferon gamma (IFN gamma) in advanced ovarian cancer is therefore of increasing interest. Permanent ovarian cancer cell lines are suitable for investigating the mode of action and the potential clinical effectiveness of such response modifiers. IFN gamma is known to modulate many cellular functions. In this study it was compared for its antiproliferative and antigen-modulatory activity on the expression of tumor-associated (CA-125, HMFG, CEA) and major histocompatibility complex (MHC) class I and II antigens as well as of the epidermal growth factor (EGF) receptor on 20 newly established human ovarian carcinoma cell lines. IFN gamma in concentrations of 10, 50 and 100 U/ml was used to study its antigen-modulatory effect, and at additional 1 U/ml and 1000 U/ml to assess its antiproliferative effect on the cells. The cells were incubated with IFN for 4 days. Two cell lines showed strong antiproliferative activity even at minimal doses (up to 50 U/ml). Intermediate growth inhibition between 34% and 84% was observed in 15 cell lines with higher doses. Three lines were resistant to IFN gamma. Independent of the antiproliferative effect, IFN gamma enhanced the expression of MHC class I and MHC class II in nearly all cell lines. Upregulation was also observed for most of the tumor-associated antigens (TAA) and EGF receptor expression. A down-regulation was noticed but rarely. The fact that IFN gamma showed an antiproliferative activity on the majority of the cell lines is of clinical relevance. The in vitro modulation of cell-surface determinants by IFN gamma warrants special attention. The enhanced expression of TAA and MHC antigens can improve immunogenicity of the tumor cells and may explain the therapeutic effects observed under IFN therapy in ovarian cancer. By contrast, enhanced expression of the EGF receptor, often associated with poor patient survival rates, may be an undesirable side-effect of IFN therapy.

p53 expression and resistance against paclitaxel in patients with metastatic breast cancer.

PURPOSE: Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate. MATERIAL AND METHODS: Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m(2 )either as first- (15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel. RESULTS: Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression ( n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response ( P=0.013). Expression of HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II did not show a correlation with the response to paclitaxel. CONCLUSION: The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.

Early postpartum hyponatremia in a patient with transient Sheehan's syndrome.

In modern day health care, Sheehan's syndrome is a rare disorder affecting the postpartum period. We present a case of a 33-year-old woman with atonic hemorrhage developing a transient Sheehan's syndrome associated with hyponatremia six days postpartum. Evaluation of cranial computer tomography and magnetic resonance imaging of the pituitary demonstrated normal finding. Immediate replacement therapy using sodium, chloride, hydrocortisone, fludrocortisone and levothyroxine revealed regression of the Sheehan's syndrome to complete recovery. The present report shows that Sheehan's syndrome can be associated with hyponatremia and illustrates the need to include hyponatremia as an initial symptom in the differential diagnosis of Sheehan's syndrome.

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.

[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]. / Erfassung angiogeneseabhängiger Parameter mittels funktioneller MRT: Korrelation mit der Histomorphologie sowie Abklärung der klinischen Relevanz als Prognosefaktor am Beispiel des Zervixkarzinomes.

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.

(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.

[Recent prognostic factors in vulvar carcinoma: histological, immunohistochemical and flow cytometry studies]. / Neuere Prognosefaktoren des Vulvakarzinoms: Histologische, Immunhistochemische und durchflusszytometrische Untersuchungen.

OBJECTIVES: Are newer histologic investigations helpful in the evaluation of the prognosis of vulvar carcinoma? METHODS: 147 primary squamous cell carcinomas of the vulva were examined for overall- and disease-free survival (mean observation 59.6 months). RESULTS: A significance in prognosis was found for FIGO-stage, a new-created histologic grade, p53- and vimentin-expression and amount of T-lymphocytes in tumoral stroma. Unfavourable prognosis was detected for tumors with elevated growth fraction, high proliferating cell-compartment (S + G2 + M) and increased cytokeratin-8-expression. CONCLUSIONS: These investigations are able to describe the malignant potential of a vulvar carcinoma and should therefore influence the decision for a modified radical therapy.

[Plastic reconstructive procedures of vulvar carcinoma: results and complications]. / Plastisch-rekonstruktive Vulvachirurgie -- Ergebnisse und Komplikationen.

PURPOSE: This study describes the results of the plastic reconstructive measures in 207 patients with a primary or a recurrent vulvar cancer. These procedures were analysed in sight of surgical excision, previous therapy, and detailed postoperative results. METHODS: All procedures and clinical parameters were recorded standardized in a data bank and analysed using statistical methods. RESULTS: In 123 local (cutaneous or fasciocutaneous) and 84 regional (myocutaneous) flaps we found a primary healing in about 2/3 of the cases. Local flaps exhibited secondary healing in 31 %, regional flaps in 20 %. This often involved the donor sites and generally did not present any permanent problems. Pronounced healing disturbances (necrosis of more than 10 %) was not achieved in local flaps, in regional flaps it aroused in 5.9 %. Gluteal femoral flaps were used most frequently and showing the best results of all myocutaneous flaps. They were comparable with the local reconstructions by a high degree of reliability and healing. In 15 cases a tissue-loss was observed. In these patients, elevated risk factors, certain oncological characteristics and technical problems could be demonstrated. CONCLUSION: Plastic surgery enlarges the spectrum of operative therapy of vulvar cancer, especially in extensive or recurrent tumors, leading to a favourable oncological outcome and good cosmetic results. Severe healing disturbances are rare and can be controlled.

Reconstructive surgery following resection of primary vulvar cancers.

OBJECTIVE: This study describes the surgical treatment and follow-up of 213 patients with primary vulvar cancer; particular attention is given to reconstructive surgical procedures. METHODS: The clinical and pathological parameters of the patients were recorded according to standardized procedures, and the data concerning type of operation, surgical reconstruction and postoperative course of disease (recurrence-free and overall survival) were analyzed. RESULTS: In about one-third of the cases, plastic surgery reconstruction involving skin-flaps was performed. In the present group of patients, plastic surgery procedures led to an elevated degree of operability as well as to more satisfactory results in terms of wound healing. For minor cosmetic defects, local (fasciocutaneous) skin-flaps resulted in excellent wound healing and short periods of in-patient treatment, even in patients with larger tumors. In cases exhibiting more severe wounds extending over larger areas of the vulva and its surrounding regions, similarly encouraging results were achieved using regional (myocutaneous) skin-flaps. CONCLUSION: The present study shows that reconstructive surgery of the vulva leads to good results in patients with vulvar cancer. Plastic surgery enlarges the spectrum of available operative therapy in vulvar cancer, especially in large tumors, and its application leads to a favorable oncological outcome as well as excellent cosmetic results in patients with vulvar cancer.

The combined operative and radiotherapeutic treatment (CORT) of recurrent tumors infiltrating the pelvic wall: first experience with 18 patients.

CORT is a new radiosurgical treatment concept for patients with recurrent gynecologic malignancies infiltrating the pelvic wall. The operative part consists of (i) staging laparotomy; (ii) maximum debulking of the tumor from the pelvic wall and exenteration of infiltrated central pelvic organs; (iii) implantation of brachytherapy guiding tubes on the residual tumor/tumor bed at the pelvic wall; (iv) pelvic wall plasty with muscle and omentum flaps to create a protective distance between the tubes and the pelvic hollow organs and to induce therapeutic angiogenesis; and (v) surgical reconstruction of bowel, bladder, and vulvoperineovaginal functions. Radiation is given postoperatively as fractionated HDR brachytherapy via the implanted tubes. Patients without prior pelvic radiation also receive preoperative whole pelvis teletherapy. Eighteen patients with recurrent malignancies infiltrating one pelvic wall have been treated with CORT in a prospective phase I/II trial at the University of Mainz. Fourteen patients had a history of radiation therapy with midpelvic doses of 40-100 Gy (median, 65 Gy) as primary treatment. Eleven patients (61%) are without evidence of disease at 6-32 months (median, 15 months) follow-up. Four patients have died from pelvic progression and distant metastases, and two patients are alive with disease after 12 months. There was no operative mortality; however, one patient succumbed from fatal thromboembolism 6 months after therapy. Three patients with prior radiation of greater than 75 Gy had to be treated for intestinal fistulas. We conclude that CORT is feasible with encouraging preliminary results.

[Current responsibilities of information processing in gynecology]. / Aktuelle Aufgaben der Informationsverarbeitung in der Frauenheilkunde.

The importance of information management systems for obstetrics and gynecology has largely increased during the last years. The reasons are increasing demands for valuable medical data for economical and medical purposes and the growing complexity of sufficient applications. Actual working fields are quality assurance in perinatology and gynecological surgery, networking, image processing and applications for artificial intelligence.

[Indications and results of reconstructive surgery of the vulva]. / Indikationen und Resultate rekonstruktiver Chirurgie der Vulva.

The surgical therapy of vulvar carcinoma requires a subtle planning. A diagnostical excision of the lesion allows the ascertainment of histologic prognosis factors. On this basis, the surgical procedures should be designed. For all surgical defects, a panel of save plastic reconstructive methods have been developed, that allows favourable functional and cosmetic results.