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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.

Objective: Screening mammography (as planned in Germany) will lead to an increasing number of breast biopsies. The purpose of this study was to determine the promise of directional large core biopsy as a patient-protecting therapeutic method., Material and Methods: 166 vacuum assisted, X-ray-guided biopsy procedures were analysed., Results: Histopathologic examination resulted in 75.8 % benign lesions. Atypical proliferation and noninvasive neoplasia was found in 18.6 %, invasive carcinoma in 5.4 % of the biopsies. Complications were few. Neither skin- or chestwall injuries, nor pain or intraoperative bleeding caused an abortion. Postoperative we found four cases of bleeding, further on in 28.3 % a superficial, in 3 % a larger and deep hematoma, but in total without any operative revision. No infection was diagnosed. In the average 17.2 (8-31) specimens were removed. After excision of 18 probes the definitive histopathologic diagnosis was clear in all cases, also, the microcalcifications were found. The underestimation rate amounted to 3 of 35 cases., Conclusions: This clinical study proves stereotactic vacuum-assisted biopsy as a relieable method for analysing indeterminate mammographically detected breast lesions, which shows lower rates of complications than conventional surgical procedures.

Objective: We compared immunohistological examination of endometrium biopsy specimen with the results of the immunohistological examination of tumor specimen to analyse the valence of this preoperative examination according to the clinico-pathological findings and overall-survival., Material and Method: Between 1985 and 1995 193 women were treated of an endometrial carcinoma at the University hospital Mainz. In this group we evaluated 41 patients with enough preoperative endometrial biopsy material for a retrospective immunohistochemical analysis and complete follow-up data. The materials from diagnostic curettage were stained and analysed for oestrogen and progesterone receptor status and for MiB-1. The results were statistically analysed using Logrank-test for overall survival., Results: The mean follow-up time was 49 months. We found a significant correlation between staining results of oestrogen (p-value = 0.0005) and progesterone (p-value=0.0003) receptor status with overall survival as well as for MiB-1 (p-value=0.05). The correlation of staining results between biopsy specimen results and tumor material from hysterectomy was 84-85 %., Conclusion: These well known prognostic factors are measurable on biopsy specimen material in same quality and high valence as on hysterectomy material.

Objective: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. -, Material and Methods: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a chi(2)-test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independence. -, Results: The mean follow-up period was 49 months. The mean age was 65 years. 21.8 % of the patients had an additional diabetes mellitus. These patients had a significantly deeper infiltration of the Myometrium (p-value = 0.004) and were more likely to have lymphonode metastasis (p-value = 0.02). -, Conclusion: Our results show a correlation between Diabetes mellitus and adverse prognostic factors witch affects by the rate of lymphonode spread and overall survival.

Objective: The purpose of this study was to determine whether the tumor suppressor gene p53 can be used as a prognosis factor to assess individual patient risk in primary ovarian carcinoma., Materials and Methods: The concentration of the mutated, as well as the wild type p53 was examined in 98 cases of ovarian carcinoma. Among 98 ovarian tumors examined, 77 were primary carcinomas, 14 tumors were metastasis of foreign tumors, and 7 were benign ovarian tumors. The pan-53 ELISA from Fa. Dianova was used to test for the p53 protein., Results: The p53 protein concentration exhibited a wide range in the different tissue samples. Benign tumors contained significantly lower p53 concentrations than malignant tumors. After the data was analyzed using Kaplan-Meier, a p53 concentration of 507.1 pg/ml was established as cut-off point for assessing cancer prognosis as good or poor. Patients exhibiting p53 concentrations over 507.1 pg/ml had a median life expectancy of 20 months, and patients exhibiting lower tumor concentrations of p53 had a life expectancy of over 70 months. A significant relationship between patient life expectancy could also be shown for tumor stage and type, whereas not for tumor grading., Conclusions: Based on the results of this study, the routine measurement of p53 may allow for a better prognostic assessment of life expectancy of patients with primary ovarian carcinoma.

Objective: The present study was to measure new prognostic factors including the plasminogen activator urokinase and the plasminogen inhibitor PAI-1, as well as p53 and Ki-67, a marker of proliferation and to compare the clinical value of these in relation to the classic histopathological prognostic factors., Material and Methods: The patient collective included 45 patients with vulvar carcinoma, both primary tumors and recurrences., Results: Highly significant correlations were found for tumor diameter and thickness. According to Kaplan-Meier estimations, the influence of thickness on the prognosis had a p-value of 0.048, while the influence of diameter had a p-value of 0.029. The variable grading was also significantly associated to the probability of survival (p = 0.01). There was no statistically significant correlation between p53 and the parameters grading, degree of keratinization and Ki-67 color index. The correlation between p53 and PAI-1 as well as between UPA and PAI-1 was highly significant. According to the Kaplan-Meier estimations, Ki-67, UPA and PAI-1 had no influence on survival in our group of patients., Conclusions: For p53, the median value could be used as a divider with the median survival of patients with a p53 below 122 pg/mg protein being 151 months and with a p53 above 122 pg/mg being only 61 months. The corresponding p-value was significant at 0.0201.

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.

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.

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.

The incidence of the carcinoma of the cervical stump is reported in the literature between 0.1-3%. The operative treatment as well as the radiation therapy is more difficult and complicated in relation to the cervical malignancy of an "intact" uterus. On the other hand the supracervical uterus-amputation offers advantages versus the classical hysterectomy. So many endoscopic experienced groups prefer this operative technique. SEMM performs an additional stanza of the cervix and corpus in order to remove the cervical adenocells. This procedure was simulated with the help of an in vitro model to answer the question of facultative adenocells in the remaining cervix. 41 uteri and the resected stanzas were histologically examined. Adenocells could be detected in 68.3 % of the cervical hulls. The transformation zone could be resected totally in all cases. Taking into account these results we can conclude, that the combination of the supracervical hysterectomy with a cervix-corpus-stanza could reduce the risk of a cervical stump-carcinoma. Because of remaining adenocells in the cervical hull, this special carcinoma-risk can't be excluded after an interval of at least 20-25 years.

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.

In 250 patients with node-negative breast cancer and no systemic adjuvant therapy the impact on the prognosis of the variables age, histological tumour type, tumour size, histological grade, receptor status and localisation of the tumour within the breast, was studied. Patients were followed over a mean period of 60 (range 7-164) months. In a subset of 124 cases additional examination of the growth fraction rate, detected by immunohistochemical determination of antibody Ki-67 and semiquantitative measurement of the stained tumour cell nuclei was performed. In 43 cases, measurement of S-phase fraction by flow cytometry was also performed. By univariate analysis, the histological tumour type (ductal/non-ductal), histological grade and growth fraction rate (< = 20%/> 20% tumour cell nuclei stained by antibody Ki-67) were found to exert a significant influence on distant disease-free and overall survival. Cox' multivariate regression exhibited histological tumour type and growth fraction rate to be independent predictors of distant disease-free and overall survival. Additionally, age was found to be an independent variable of distant disease-free survival. Measurement of growth fraction rate by immunohistochemical detection of Ki-67 antigen is a fairly simple and easily applicable procedure. It should be discussed whether a growth fraction rate of more than 20% could be an indication for adjuvant chemotherapy in patients with node-negative breast cancer.

In spite of the development of various techniques for the formation of a neovagina, the longterm results are often disappointing, especially if the simpler methods (dilation, ectopic pouch formation, epithelium transfer) have been applied. The more complex surgical techniques such as musculo/fasciocutaneous and colon flaps are associated with a significant risk of severe complications. For certain operative situations necessitating vaginal reconstruction, adequate procedures are still missing. Based on surgico-anatomic investigation of the vascular territories of the myoperitoneal anterior abdominal wall, we introduce the use of myoperitoneal composite flaps from the deep inferior epigastric artery angiosome as a novel surgical principle for vaginal reconstruction and report on the experience with the first two patients.

The occurrence of the p 53 gene mutation in breast carcinoma tumour cells, leads to the accumulation of mutant p 53 protein types, whose consequence is the loss of the negative regulation normally exercised by the p 53 gene, which is considered to act as a tumour suppressor. It is possible to demonstrate the presence of mutant p 53 protein types in tumour cell nuclei by applying immunohistochemical procedures to paraffin sections (Clon DO 1, Dianova). We tested 482 primary breast carcinomas for the presence of these proteins, and positive immunohistochemical findings for mutant p 53 proteins were recorded in 21.6% of the cases. In another 14.3% of these breast carcinomas, less than 10% of the tumour cells exhibited positive staining. In the other 64.1% of cases, the immunohistochemical findings for p 53 proteins were entirely negative. Independent of the immunohistochemical staining results, we performed a retrospective analysis of the disease course of this group of primary breast carcinomas: it emerged, that p-53-positive breast carcinomas had a significantly less favourable prognosis as compared to primary tumours, which were negative or weakly positive for this protein group. The accumulation of p 53 proteins in tumour cell nuclei is correlated with negative oestrogen- and progesterone-receptor status, as well as with the degree of proliferation exhibited by the breast carcinoma. Such accumulation is, in contrast, unaffected by the tumour stage, its histological grading, menopausal status, and the overexpression of c-erb B2.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

With regard to clinical diagnosis and prognosis, intrauterine infection continues to pose major problems for obstetricians. In recent years serum assay of CRP, an acute phase protein, has become firmly established in the obstetric management of premature rupture. We investigated the relationship between histologically confirmed chorioamnionitis and maternal and fetal inflammation parameters in 69 patients on the basis of inflammation of the membranes, placenta and cord occurring in histomorphologic stages. Our results show the C-reactive protein to be a sensitive and specific indicator of chorioamnionitis and closely correlated with both the histologic stage and the severity of the chorioamnionitis. We therefore advocate adoption of the histologic result as the "gold standard" for evaluating subclinical and clinically manifest forms of intrauterine infection.

The discussions on the pros and cons of obstetric screening for connatal infections have been going on for years. We, therefore, conducted a prevalence study of the most common connatal infections. HIV infection, rubella and syphilis were not subjects of this study. We analysed the relevance of these infections in 512 pregnant women and their newborn infants at the moment of delivery. Further serological tests were run three months post partum, if necessary even for a longer period. Cytomegaly IgG antibodies were found in 46% of the examined women, IgM antibodies in 1.3%. Women under the age of twenty and women of low social standing showed the highest rate of prevalence of infection with CMV. The prevalence of IgG antibodies against parvovirus B 19 was 29%. In 10 mothers, positive IgM titers were found at the time of delivery. In all these women, pregnancies had been uneventful. However, 9 mothers exhibited a significantly raised abortion rate within the last 20 months before delivery. 7 of 512 women turned out to be HBs antigen carriers, 3 women and their babies were anti-HCV positive. The prevalence of toxoplasmosis IgG antibodies was 36%, of IgM antibodies 5.3%. By further investigation (Toxo ISAGA, Toxo IgA) we were able to detect one child with connatal toxoplasmosis. We conclude, that screening for parvovirus B 19 and hepatitis C is required only, if there are contact or clinical hints that the patients might have acquired either one of these infections. But we postulate, that a routine screening programme for hepatitis B and toxoplasmosis should be carried out in all pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)

Between 1984 and 1990, twenty-four patients suffering from advanced primary (7) or recurrent (17) valvular carcinoma were treated by posterior exenteration and myocutaneous reconstruction of the defect. During a follow-up of 34 months, the overall survival was 49%. Eight patients died. Tumour diameter and tumour-free margins of the resected specimens were the most important prognostic factors. In all cases, an improved quality of life could be achieved by the operation. It is concluded that, even in extremely difficult situations, posterior exenteration, followed by plastic reconstruction entails an essential benefit for the patient.

Cardiotocography (CTG) is to be considered today's most sensitive monitoring tool for the functional surveillance of placental performance during parturition. 351 cardiotocographically monitored singleton pregnancies were used as patient material for fine tissue examination of the state of maturity of the villi of the relevant placentas. In histological assessment, placental diagnoses are allocated to defined CTG changes; in particular, however, the identification of reserves, capable of maturing (immature intermediate villi in the centres of the placental subdivisions or placentones), is subject to separate scrutiny. The following results emerge clearly: terminal placentas without maturing potentials, prematurely matured placentas and placentas with deficiency of terminal villi, as well as the absence of immature intermediate villi in the centers of the placentones, are connected with a suspected prepathological or pathological CTG assessment. The histological groups have the lowest incidence of the normal oscillatory type and normal oscillatory frequency and have the highest proportion of abnormal CTG assessments according to the Hammacher score. The absence of the identification of potential maturing reserves (immature intermediate villi) is associated with the highest incidence of Caesarean sections (29.8%). These results show, that the physiological maturing potentials (immature intermediate villi) which can be identified up to term are a histological indication towards regular placental performance, even in labour.

We investigated the oestrogen-receptor content (ER-ICA) of 614 tissue samples taken from breast carcinomas (all obtained from patients at the Universitäts-Frauenklinik, Mainz FRG) using immunohistochemical procedures. Since the findings of follow-up studies as well as estimates of survival probability (according to the procedure of Kaplan-Meier) for 334 of the primary breast carcinomas were available, it was possible, to assess the prognostic value of the immunohistochemical results. The percentage of receptor-positive tumour cell nuclei (i.e. the heterogeneity of the tumour), as opposed to the staining intensity, proved to be the most useful criterion of the IRS, whose cut off level was determined as being IRS 1. Regardless of their lymph node status, mammary carcinomas which were immunohistochemically positive for estrogen receptors, were found to have a significantly better short-term prognosis, than breast tumours which were negative for such receptors. In the case of certain breast carcinomas exhibiting contradictory findings (i.e. ER-ICA positive but biochemically negative for oestrogen receptors), the present immunohistochemical method provided the most accurate assessment of the biological behaviour and development of the tumor. Therefore, ER-ICA represents a valuable prognostic criterion, which when complemented with PR-ICA, should facilitate attaining optimal selection of patients suitable for endocrine therapy.

In 147 primary breast carcinomas, over-expression of NEU-protein was detected immuno-histochemically. 20 tumours (13.6%) showed a positive reaction. Correlations with established prognostic factors, showed a significant relationship to unfavourable histological grading and negative oestrogen receptor status, as well as to the negative status of both oestrogen and progesterone receptors. However, no correlation could be demonstrated with the progesterone receptor alone. Only a trend without significance was demonstrated to the tumour size and proliferation rate-indicated by the Ki-67 antibody. No correlation existed to the status of the axillary nodes. Overexpression of NEU-protein proved to have a significant influence on the disease-free survival and overall survival in a median follow-up time of 31 months. Nevertheless, this could be shown only for tumours with metastasis in axillary nodes, but not for nodal negative tumours. A possible Longer follow-up time is necessary, to show a difference of results for the latter group.

245 breast cancer tissues were analysed immunohistochemically, using monoclonal antibody Ki-67, which spezifically reacts with a nuclear antigen of proliferating cells and represents the so-called growth fraction. According to the number of positive cells, three Ki-score categories (I-III) were established. The results were compared with prognostic variables (Histological grading, DNA-cytophotometry), staging parameters, immunocytochemical (ER-ICA, mPRI), and biochemical (DCC) hormone receptor assay. We found a good correlation between Ki-67 and grading (Bloom and Richardson): G 1-tumors had small growth fractions, in contrast to G-III carcinoma, which showed a high percentage of Ki-Score III. Receptor negative cases had a large growth fraction and receptorpositive ones showed an uniform distribution. The comparison between Ki-67 and tumor spread or DNA-Cytophotometry showed no correlation. The majority of 31 recurrent tumors not only had a large number of positive cells, but also a definite dependence was found between Ki-Score and length of the disease-free period. Ki-67 seems to be an important immunohistochemical marker of breast cancer, which contributes to the individual assessment of the disease and can possibly give predictions on tumor development and response to radiation and systemic therapy.