[Innovative concepts for surgical treatment of the carcinoma of the breast]. / Innovative Konzepte zur operativen Behandlung des Mammakarzinoms.

Breast conserving therapy is a stable element in primary breast cancer treatment. Conservation and also restoration of the breast improve the outcome concerning psychological aspects. Surgical interventions include techniques for classical breast conservation as well as oncoplastic procedures like reduction mammaplasties and different types of flaps. Theses modern surgical procedures should be realised in a breast center.

[Plastic surgery of defects of the thoracic wall]. / Plastische Deckung von Thoraxwanddefekten.

Defects of the thoracic wall are mostly due to a malignant disease of the mammary gland. Radiotherapy is one of the essential methods of treating cancer of the breast in addition to primary surgery. If, after surgery, healing occurs by secondary intention or if there is a local recurrence or tumour formation in the thoracic wall due to irradiation, the body's reserves of soft parts are often exhausted and the adjacent tissue has been additionally damaged by the irradiation. General principles of treatment in the management of such problems are presented by means of several case reports.

[Clinical and chemical laboratory course of HELLP syndrome--a retrospective analysis]. / Klinischer und laborchemischer Verlauf des HELLP-Syndroms--eine retrospektive Analyse.

The HELLP-Syndrom (hemolysis, elevated liver enzymes, low platelet count) is considered as a severe complication of eclampsia with unpredictable development of pregnancy including high maternal and fetal risk. The result of retrospective analysis of all deliveries of the years 1986-1991 at the UFK Marburg were 28 cases of proved HELLP-Syndrom. Medical history, correlation of clinical and laboratory findings as well as the development of the disease and the neonatal dates were evaluated by computerized documentation. The incidence of HELLP-Syndrom was 28 of 8111 deliveries at all (0,34%). 82% of the women with HELLP-Syndrom were primiparae. The leading symptom was right upper abdominal pain in 75%, which lasted already 5,7 days before presentation in the clinic. Hypertonus, edema and proteinuria were present in 71%, 61% and 89% of the cases. The diagnosis indicating laboratory finding was the thrombocytopenia (mean 62 G/l). In comparison to the thrombocytes, which were at the 4.-7. day pp in 89% within the normal range, the liver function tests normalized just between the 9. and 13. day pp (SGOT 89%, SGPT 77%). The shortening of the prepartal hospitalization from 6 days in 1986/87 to 8 hours in 1990/91 decreases the periand postnatal complication rate from 43% to 23%. 26/28 patients (92%) were delivered by caesarean section from healthy babies through which were 75% premature infants and in 27% of the cases small for gestational age additionally. We conclude that the decrease of the diagnosis-delivery interval and the intensive medical care are responsible for the diminution of the maternal and neonatal mortality rate to 0%.

Androgen-like and anti-androgen-like effects of antiprogestins in human mammary cancer cells.

In addition to their antiprogestational activity, the antiprogestins RU486, ZK98.299 and ZK98.734 possess varying antiglucocorticoid as well as androgen-like or antiandrogen-like properties in human mammary cancer cells. The human mammary cancer cell line MFM-223, which contains only androgen receptors, was used as a model to investigate androgen receptor mediated effects of these antiprogestins. Proliferation of MFM-223 cells is inhibited by androgens and does not respond to oestrogens, progestins and glucocorticoids. As shown in proliferation assays, ZK98.734 was a strong inhibitor of cell proliferation. This effect was antagonised by the antiandrogen hydroxyflutamide. ZK98.734 was found to displace [3H]R1881 from the androgen receptor in MFM-223 cells, substantiating the involvement of the androgen receptor. The antiprogestin ZK98.299 failed to influence the proliferation of MFM-223 cells. ZK98.299 did not bind to the androgen receptor and was devoid of androgenic or antiandrogenic activity. RU486 bound to the androgen receptor. It was a weak inhibitor of MFM-223 cell proliferation, but the inhibition of proliferation by RU486 was not antagonised by hydroxyflutamide. This effect was probably not mediated by the androgen receptor. RU486 had antiandrogenic activity in this cell line, as it antagonised the inhibitory effect of dihydrotestosterone at a 100-molar excess. These results were confirmed by transfection experiments with an MMTV-CAT construct in the same cell line, demonstrating the biological function of the ZK98.734-androgen receptor complex. ZK98.299 and RU486 were not able to induce CAT activity. The different androgenic or antiandrogenic properties of the antiprogestins investigated should be considered when selecting antiprogestational properties of the antiprogestins investigated should be considered when selecting antiprogestational compounds for clinical applications, as a partial androgenic activity may be of benefit in breast cancer but can have undesired side-effects in other diseases.

Diagnostic value of pelvic examination, ultrasound, and serum CA 125 in postmenopausal women with a pelvic mass. An international multicenter study.

BACKGROUND: In a prospective study, the differential diagnostic potential of pelvic examination, ultrasound, and serum CA 125 assay in postmenopausal patients presenting with a pelvic mass was assessed. METHODS: A total of 228 patients were evaluated preoperatively in an international, multicenter, prospective study using a standard protocol for pelvic examination, transvaginal (occasionally additional abdominal) ultrasound, and serum CA 125 determination with a cut-off level of 35 U/ml. RESULTS: Ninety-five malignant (41.7%) and 127 benign (55.7%) pelvic tumors were found in addition to 6 borderline ovarian tumors (2.6%) in the 228 patients. Seventy-two patients had ovarian carcinoma, 49 of whom were International Federation of Gynecology and Obstetrics Stage III or IV. Borderline tumors were excluded from the statistical calculations. The individual accuracy of pelvic examination, ultrasound, and serum CA 125 in discriminating between benign and malignant pelvic masses was approximately the same (76, 74, and 77%, respectively). Using logistic regression analysis, the power of pelvic examination appeared to be the most relevant factor (adjusted odds ratio, 9.2), followed by serum CA 125 (odds ratio, 5.6), and ultrasound (odds ratio, 4.9). Age appeared to be nonpredictive. No cancer was found in any patient in whom all three methods scored negative (n = 53; positive predictive value for malignancy = 0 and 95%; confidence interval, 0-7). CONCLUSIONS: The combined use of pelvic examination, ultrasound, and serum CA 125 leads to improved discrimination between malignant and benign pelvic masses, because malignancy can be excluded when all three examination methods are negative. A change to a more patient-tailored surgical approach could be considered in those cases.

The response of uterine fibroids to GnRH-agonist treatment can be predicted in most cases after one month.

Twenty-seven patients with uterine fibroids were treated for 3 months with the GnRH-agonist goserelin prior to surgical myomectomy. Ovarian function was suppressed reliably in all patients. After three applications, 15 fibroids were reduced in volume by more than 50%, and one complete remission was achieved. Seven patients showed a decrease of 10-50% in volume. However, in 5 cases there was no significant reduction. Analysing the time course of the fibroid reduction, the response can be predicted in most cases as early as four weeks after the first injection. Retrospective statistical analysis showed that a 50% reduction in fibroid size due to GnRH treatment is preceded by a 35% reduction after 4 weeks in 81% of cases, and after 8 weeks in all cases. Only 2 of 12 fibroids, which showed a smaller response (less than 50%) to GnRH therapy, were reduced by more than 35% after 4 and 8 weeks. In most cases it seems to be possible to estimate the individual response to GnRH-application after the first injection, so that it is possible to stop therapy in non-responding patients.

[Condylomata acuminata and associated infections--possibilities for therapy with interferon]. / Condylomata acuminata und assoziierte Infektionen--Möglichkeiten der Therapie mit Interferon.

Recombinant alpha-Interferon can be used in primary therapy of condylomata acuminata. In our patients we found a response rate of 53%. Besides use in primary therapy the significant low rate of recurrences is important, thus offering the possibility of adjuvant interferon therapy after primary surgical treatment, where laser-vaporisation is best applied. Possible applications for primary and secondary treatment are shown. The rate of additional infections is of great importance; besides common agents for vaginal infections we found an elevated rate of HPV 16/18 with 47%.

C-reactive protein is a marker for the diagnosis of adnexitis.

The study reports the C-reactive protein (CRP) plasma concentrations in 115 women with a presumed diagnosis of acute adnexitis. In addition to CRP, blood sedimentation rate, white blood cell count and the body temperature were evaluated and compared with the clinical findings. Diagnosis was confirmed or excluded by laparoscopy (n = 69) or laparotomy (n = 9). Clinical examinations and conventional laboratory examinations were of limited value in the diagnosis of acute adnexitis. In contrast, CRP was a highly sensitive indicator of inflammatory pelvic disease. Furthermore, the CRP determination was superior in assessing the efficacy of an antibiotic treatment.

[Interferon in the treatment of condylomata acuminata]. / Interferon in der Behandlung von Condylomata acuminata.

In the present study we used the well known antiviral properties of interferon alpha 2b in condylomata acuminata. Firstly we investigated 3 different application forms. We found that 1. the local INF application in gel was completely ineffective, 2. the injection of INF into the base of the warts was effective but too painful for routine therapy, 3. the systemic treatment by s.c.-injection had an excellent compliance and a high efficacy. In the second part of the study we treated 16 patients with our own s.c.-regimen of 3 x 5 mill. U and 6 x 2 mill. U INF alpha 2b within 5 weeks. 60% showed a complete response, 30% a partial response; these were treated surgical afterwards. In none of the patients a relapse occurred at a median follow-up of 11 months. The observed side-effects were poor. We consider the systemic treatment with interferon for condylomata acuminata to be highly effective and well tolerated. The relapse rate is very poor.

[The importance of the SCC antigen in the diagnosis and follow-up of cervix carcinoma. A cooperative study of the Gynecologic Tumor Marker Group (GTMG)]. / Bedeutung des SCC-Antigens in der Diagnostik und Verlausfskontrolle des Zervixkarzinoms. Eine kooperative Studie der Gynäkologischen Tumor-Marker-Gruppe (GTMG).

SCC (squamous cell carcinoma) antigen is a subfraction of tumour antigen TA-4 isolated from cervical squamous cell carcinomas. Serum concentrations of SCC antigen were measured by radioimmunoassay in 382 control subjects, 70 women with cervical intraepithelial neoplasia (CIN), 517 with cervical carcinoma and 203 with other gynaecological carcinomas. Elevated SCC antigen levels (greater than 2.5 ng/ml) were found in 4% of normal controls, in 7% of women with CIN I-III, in 2%-23% with various forms of genital adenocarcinomas, in 55% with primary and in 76% of those with recurrent cervical squamous cell carcinoma. The positivity rate of the antigen was correlated with tumour stage (FIGO) and lymph node involvement of primary cervical squamous cell carcinomas. During long-term follow-up serum levels of SCC antigen were found to be concordant with tumour activity in 74% of cases. Patients with still elevated marker levels after therapy had twice the recurrence rate of women with normal serum values. Routine determination of SCC antigen during follow-up of cervical cancer is recommended.

Squamous cell carcinoma antigen for monitoring cervical cancer.

The tumour-associated antigen was determined in the plasma of patients with squamous cell carcinoma (SCC) of the uterine cervix by radioimmunoassay. Setting a limit of 2 ng/ml, levels were abnormal in 13.4% of healthy controls, in 14% of patients with carcinoma in situ and in 62% of patients with invasive cervical SCC. The incidence of elevated SCC antigen levels and the absolute antigen plasma concentration were dependent upon the tumour load, increasing significantly with advanced stage disease. Abnormal SCC antigen values in operable cervical cancer declined to normal within one week after radical hysterectomy with pelvic lymphadenectomy. In cases of radiotherapy antigen values took 4-6 weeks after the start of treatment to return to normal. The success of both treatment modalities was announced by an early rise in the SCC antigen in the initial phase of therapy, followed by normalisation. After successful primary treatment and a complete remission during further follow-up SCC antigen in plasma was only increased in 3.8% of the cases. Retrospective evaluations in ten patients with progressive disease showed the reappearance of abnormal SCC titers and further increase preceeding the clinically detectable relapse or progression, with a median interval of 8 weeks. The present study indicates that SCC antigen determination is not useful for the early diagnosis of cervical cancer, but it is a potential means for monitoring the efficacy of individual anticancer therapy of SCC of the uterine cervix and for detecting recurrent disease.

CA 15.3 as a tumour marker in breast cancer.

CA 15.3 is an antigenic determinant associated with human mammary carcinomas. Two murine monoclonal antibodies have been raised against the determinants, and an immunoradiometric assay (IRMA-Kit, Centocor, USA) has been developed to determine the antigen levels in plasma of cancer patients. Based on the 99% confidence limit of healthy women, plasma values above 30 U/ml are considered abnormal. Plasma samples from 357 women were examined in the present study. Healthy females (n = 84) ranged below the cut-off level between less than 10 and 29 U/ml. Higher values were found in 12.5% of benign breast diseases and in 23.6% of breast cancer patients, including all stages. Depending on the stage of the disease, there were elevated levels in 11% of operable breast cancer patients preoperatively, in 7% of the cases with no evidence of disease after primary treatment and in 63.5% of patients with disseminated mammary carcinoma. In metastasized breast cancer the frequency and the degree of abnormal titers were closely related to the extent of the metastatic disease. Follow-up examinations of 63 patients under cytotoxic therapy showed CA 15.3 changes correlating well with the clinical course in up to 90% of the antigen positive cases. The present data indicate that CA 15.3 may be useful in the surveillance of breast cancer patients. However in our study one third of the patients with metastatic breast cancer did not show any increase in CA 15.3 and must be regarded as antigen negative.

[Monoclonal antibodies in the diagnosis and follow-up of ovarian cancer. CA 125 as a tumor marker. A cooperative study of the Gynecologic Tumor Marker Group (GTMG)]. / Monoklonale Antikörper in Diagnostik und Verlaufskontrolle des Ovarialkarzinoms. CA 125 als Tumormarker. Eine kooperative Studie der Gynäkologischen Tumormarkergruppe (GTMG).

The clinical validity of using the cancer antigen (CA) 125--a surface antigen on malignant epithelial ovarian tumors--for diagnosis and follow-up of ovarian cancer was investigated in a cooperative study. Using a monoclonal antibody (OC 125) to detect CA 125, the sera of 850 patients were analyzed by immunoradiometric assay (IRMA-Kit Centocor). For 199 patients with ovarian cancer, a preoperative sensitivity of 83% and 74% resulted for the usual cut-off points (greater than or equal to 35 and greater than or equal to 65 U/ml respectively). The positivity rates and quantiles correlated with the stage of disease (FIGO) and with the tumor debulking achieved at primary surgery. The most frequent histological types (serous cyst-adenoma and the undifferentiated carcinoma of the ovary) showed the highest positivity rates (80% and 90%, respectively, for cut-off at greater than or equal to 65 U/ml). Elevated CA 125 values were found in 74% of the cases with a relapse and in 79% of the patients with advanced disease (cut-off, greater than or equal to 65 U/ml) in the follow-up of ovarian cancer. We recommend cut-off at greater than or equal to 65 U/ml, because the values for only 1% of the female healthy controls (n = 251) were above this level. Also 17% of the patients with adnexitis and 8% with benign neoplasias of the ovary showed elevated titers. Therefore CA 125 should not be used for mass screening of ovarian carcinoma. However, it is a helpful laboratory tool in the diagnosis of recurrence and the surveillance of patients with ovarian cancer.

The effect of combination chemotherapy on ovarian, hypothalamic and pituitary function in patients with breast cancer.

Treatment of breast cancer by combination therapy induced luteal insufficiency, anovulatory cycles and sometimes hypergonadotropic amenorrhea in premenopausal women with previously normal mentrual cycles and ovarian function. In chemotherapy induced amenorrhea 17 beta-estradiol levels were those found in ovarectomised or postmenopausal women. Chemotherapy affected the ovary itself and not the hypothalamus or pituitary, the negative feedback mechanisms remaining intact. The ovary of perimenopausal patients was much more sensitive to cytotoxic drugs; following a short time chemotherapy hypergonadotropic amenorrhea invariably developed and the ovary seemed to be again the prime site of action. Postmenopausal patients continued to have physiologically high LH and FSH plasma concentrations and low plasma levels of prolactin and 17 beta-estradiol under cytotoxic treatment.