Term and role of tumor centres in oncology healthcare in Germany.

Breast cancer is the most common malignant disease among women in Germany. There are more than 50,000 new cases of breast cancer diagnosed each year in the country. As breast cancer is a complex disease it necessitates an interdisciplinary treatment, therefore it is very likely that patients with breast cancer will benefit from treatment in special centers, either a "breast cancer centre" or "tumor centre". In recent years certifying programs for the above mentioned centers have been introduced, which guarantee standards of the quality of treatment for breast cancer all over the country. In this article we report on the development and role of tumor centers in oncology healthcare in Germany, which nowadays have a very good international reputation. Moreover, they may be a good example to other countries to found similar centers in order to improve standards of the management in oncology healthcare.

Changes in satisfaction in patients with gynaecological and breast malignancies: an analysis with the Socio-Economic Satisfaction and Quality of Life questionnaire.

Quality of life (QOL) is commonly assessed using health-related questionnaires. The Socio-Economic Satisfaction Quality of Life (SES-QOL) questionnaire includes specific individual coping topics, such as health, leisure activities, sexual life, occupation, financial situation, partnership situation, family situation, accommodation situation and friendship situation. This paper reports the findings of the survey with the SES-QOL with an emphasis on changes in satisfaction during the course of a disease involving a gynaecological or breast malignancy. From February 2000 to October 2002, 1030 women diagnosed with breast or gynaecological cancers were included in this study. The patients responded to the SES-QOL questionnaire as part of an interview. Metastatic disease results in more frequent reporting of dissatisfaction with health issues (63%), sexual life (24.5%) and occupation (20%), whereas patients in the adjuvant setting report deteriorating satisfaction with regard to health (41.7%), sexual life (12.2%) and occupation (11.5%). The SES-QOL reflects individual changes in different aspects of satisfaction during the course of a cancer disease. Identifying as many causing variables as possible, and offering support through an interdisciplinary approach including the physician, a social worker and a psycho-oncologist, appears necessary in order to help patients cope with cancer as a dynamic and individual process.

Predictors for long-term survival after interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers.

BACKGROUND AND OBJECTIVES: We wanted to identify factors which allow predicting long-term survival after pelvic exenteration (PE) for locally advanced or recurrent gynecologic malignancies. METHODS: All patients undergoing PE at our institution from 1983 to 2002 were screened. In 203 cases data were obtainable and analyzed with respect to factors predicting outcome considering morbidity, mortality, and survival. Follow-up data and data concerning late complications not documented in our records were obtained by telephone interviews. RESULTS: Mean age was 55 (22-77) years. PE was performed for locally advanced (36%) or recurrent (64%) cervical (n = 133), endometrial (n = 26), vaginal (n = 23), vulvar (n = 10), and ovarian cancer (n = 11, cases with rectum and/or bladder resections). In 13.4% (n = 26) the intent of the procedure was palliation in the remaining cure. Procedures performed were anterior (n = 91), posterior (45), or total (n = 67) PE. 53% of patients underwent preoperative radio-chemotherapy, 11.8% as a neoadjuvant treatment. Mean OR time was 8.1 hr, an average of 5.6 units of packed red blood cells were perioperatively transfused. Microscopically complete resection was achievable in n = 69 patients. Perioperative mortality was 1% (n = 2). Seventy-one percent (n = 144) of patients were available for follow-up. Five-year overall survival in patients treated with a curative intent was 21%, 5-year survival in those patients with complete resection was 32%. Forty-two percent of patients with a complete resection without lymph node involvement, age 30-50, curative intention, and the absence of a pelvic sidewall infiltration survived 5 years or longer. CONCLUSION: In our series a 5-year survival rate of over 40% could be achieved for nodal-negative patients without pelvic sidewall infiltration when treated with curative intent and after complete resection.

[Mona Lisa syndrome: idiopathic facial paralysis during pregnancy]. / Das Mona-Lisa-Syndrom--die periphere Fazialisparese in der Schwangerschaft.

Mona Lisa has been pregnant shortly before the famous painting of Leonardo da Vinci was created (1503-1506). Recently, it has been speculated that Mona Lisa's famous smile is caused by facial muscle contracture and/or synkinesis after Bell's palsy with incomplete nerval regeneration. During pregnancy the incidence of Bell's palsy is increased up to 3.3 times compared to nonpregnant women. The etiology, associated factors as well as various treatment options aiming at the prevention of associated complications and improving recovery of facial nerve function have intensively been evaluated over the past three decades. However, the preferred mode of therapy management, particularly in pregnant women, remains undecided. Corticosteroids may be beneficial if they are applied after the first trimester.

Use of intensified early cancer detection in high-risk patients with familial breast and ovarian cancer.

A prospective follow-up study was carried out to evaluate the influence of risk and genetic counselling on use of early cancer detection. Five hundred and fifty-six subjects who fulfilled inclusion criteria for a genetic analysis of the BRCA1/2 genes (the high-risk group A) and 205 who did not fulfil the inclusion criteria (the lower risk group B) attended primary consultation in the interdisciplinary cancer genetic clinic. Information about participation in the early cancer detection programme was documented. Information about changes in use after consultation could be evaluated from 349 women (94 group B and 255 group A). Methods such as monthly self-palpation, breast palpation by gynaecologist, ultrasound of the breast, transvaginal ultrasound and pelvic examination had all been commonly used. Consultees at higher risk used mammography less often than women at lower risk. Magnetic resonance imaging of the breast was used rarely. Most methods were used more often at the recommended interval by women at higher risk during the follow-up period. In conclusion, at present intensified early cancer detection programmes for women at risk provide a less invasive option than chemoprevention or prophylactic surgery. Although the methods are used at high frequency it seems feasible to motivate women at risk to participate. This can be done by providing information and counselling in the cancer genetic clinic.

The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia.

Hereditary risk determinants of venous thrombosis have been reported to be associated with severe preeclampsia. So far there are no data to support whether these risk determinants are related to the time of onset of severe preeclampsia. We used a case-control design, studying 97 women with severe preeclampsia in previous pregnancies and 277 normal women, to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. A case-only design comprising solely the 97 women with a history of preeclampsia was used to evaluate these risk factors as risk determinants for early onset of severe preeclampsia. Using the case-control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia [factor V Leiden, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.4, 2.2; prothrombin mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT genotype, OR 0.8, 95% CI 0.4, 1.8; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.2, 95% CI 0.7, 2.1; PAI-1 5G/5G genotype, OR 1.0, 95% CI 0.5, 1.8]. However, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.1 weeks, P = 0.046) and in women with the PAI-1 5G/5G genotype (25.7 weeks vs. 30.8 weeks, P = 0.024). Hereditary risk factors for venous thrombosis do not predispose for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI-1 5G/5G genotype are at risk for early onset of severe preeclampsia. It appears that these risk factors do not induce the pathomechanism but accelerate the course of preeclampsia.

Awareness of breast cancer incidence and risk factors among healthy women.

The efficacy of early breast cancer detection programmes seems to be mainly influenced by the awareness of breast cancer in general among healthy women. This study aimed to provide information about women's understanding of breast cancer incidence and risk of disease. Based on a newly developed questionnaire 2108 healthy women were asked about their knowledge and perceptions in relation to breast cancer incidence, risk factors, risk perception and level of concern. Of these women 78.8% were well aware of breast cancer in general terms. However, there were major aspects such as incidence or risk factors that were poorly understood. Only one-third correctly estimated the incidence of breast cancer; 95% understood breast cancer in the familial history as a risk factor, but only 57% understood the age risk; 37.1% of women perceived hormonal contraceptives and 35.9% hormonal replacement therapy as risk factors of breast cancer. The latter estimation was significantly higher in women above 40 years. Recommendations for the improvement of cancer prevention programmes include targeting understanding of lifetime risk of breast cancer, age as a risk factor, survival from breast cancer or hormonal factors. There is a need to separately address the perceptions of women depending on age, social status and educational levels.

[Symptoms and therapy for pregnancy rhinitis]. / Klinik und Therapie der Schwangerschafts-Rhinopathie.

Pregnancy rhinitis is a common condition with long-lasting nasal congestion without signs of infection, allergy or tumor, starting at any time during pregnancy and disappearing completely within 2 weeks of delivery. Risk factors are smoking, sensitisation to house dust mites and chronic sinusitis. Hormonal influences are most likely; however, a definitive pathophysiological concept does not exist. Various treatment options are presented and a stepwise therapeutic strategy for pregnancy rhinitis is developed.

Molecular mechanism of estrogen receptor (ER)alpha-specific, estradiol-dependent expression of the progesterone receptor (PR) B-isoform.

The physiological effects of progesterone are mediated by the progesterone receptor (PR) isoforms PRA and PRB, transcribed from a single gene, under control of two distinct promoters. Both the isoforms display different, promoter- and cell line-specific transactivation properties. Upregulation of both isoforms in response to estradiol stimulation has been described, although the two promoters contain no classical estrogen response element (ERE). Therefore, we decided to investigate the regulation of PRB-expression through distinct estrogen receptor (ER)-isoforms: ERalpha and ERbeta We demonstrate, that in HeLa cells treated with E2, PRB promoter activity was enhanced (five-fold) by ERalpha, but not by ERbeta. ERbeta was also unable to stimulate activity of the PRB promoter in BT20 and Ishikawa cells, where ERalpha induced reporter activity by two-fold. Deletion of the AF1-but not AF2 domain from ERalpha resulted in loss of the transactivation potential in all cell lines tested. Furthermore, in BT20 cells deletion of the AF2 domain of ERalpha resulted in stronger transcriptional activation than that mediated through wild-type ERalpha. In SK-BR-3 cells both ERs repressed PRB promoter activity and this repression was enhanced by co-transfection of SRC1. However, strong estrogen-dependent stimulation was observed after deletion of AF2. We conclude that PRB expression is stimulated by ERalpha but not ERbeta in an unique, AF1-dependent but AF2-independent mechanism.

[Interdisciplinary aspects of surgery of the pelvis minor and retroperitoneum]. / Operative Interdisziplinarität-Kleines Becken und Retroperitoneum.

Surgery of diseases of the pelvis minor and retroperitoneum such as inflammatory disease, malignant tumours, or trauma of pelvic organs need the close interdisciplinary collaboration of visceral surgeons, gynaecologists, and urologists. This collaboration begins in planning diagnostic and therapeutic procedures. It has to be clear who performs which operative step and when. Excellent long-term results in malignant disease show that the greater effort is worthwhile. The rate of postoperative morbidity after these multivisceral resections is high also in specialised centers, but mortality is below 5%. Because of the growing number of long-term survivors, preservation of quality of life becomes more and more important.

Insights into the molecular biology of the estrogen receptor define novel therapeutic targets for breast cancer.

Evidence for a role of ovarian factors in the growth of metastatic breast cancer was first recognized over 100 years ago. Today, anti-estrogens are central to the treatment of breast cancer of all stages. We now understand that the action of estrogen is mediated by the estrogen receptors (ER) which are members of the nuclear receptor family of ligand-regulated transcription factors. In this article we review the molecular mechanisms through which ER activates transcription of target genes and through which available anti-estrogens mediate their therapeutic effects. We discuss possible mechanisms of failure of treatment with current anti-estrogens and how newer anti-estrogens under development attempt to address these problems. In addition an expanded view of the molecular mechanisms of estrogen action is leading to the development of novel selective ER modulators or SERMs.

Expression of the hyaluronan receptor RHAMM in endometrial carcinomas suggests a role in tumour progression and metastasis.

PURPOSE: Interactions of hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) have been proposed as being important in promoting tumour progression and dissemination. This comparative study was designed to investigate the RHAMM expression patterns in endometrial carcinoma. METHODS: We examined a series of 89 endometrial carcinomas and 15 normal endometrial tissues by immunohistochemistry, using a RHAMM-specific polyclonal antibody. Expression of RHAMM was assessed according to the pattern and intensity within (overall cytoplasm, center/periphery of tumours) and between the tumours. The staining results were compared to the corresponding clinical data (age, menopause status, histological staining, histological grading, lymph node status). RESULTS: RHAMM-expression was detectable in 58% of the 89 tumours [Histological stage: pT1a (8/12); pT1b (16/37); pT1c (18/26); pT2 (6/9); pT3a (4/5)] and 13% (2/15) of the normal endometrial tissues. The positivity rates for RHAMM were 100% in patients with positive lymph nodes but only 50.7% in patients with negative lymph nodes ( P<0-01). Additionally, the expression pattern showed a highly significant correlation ( P<0.01) with the histological grade of the tumours [G1 (6/42), G2 (33/34), G3 (13/13)] and occurrence of lymph node metastases. CONCLUSIONS: Our results suggest that RHAMM expression may enhance and improve the invasion and metastasis of endometrial carcinomas.

Herpes gestationis may present itself as a paraneoplastic syndrome of choriocarcinoma-a case report.

BACKGROUND: Herpes gestationis (HG) is a rare, recurrent, pruritic, vesicobullous dermatosis occurring predominantly in pregnancy and seldom in early puerperium. Reports of the association of HG with choriocarcinoma are extremely rare and this case highlights such a possible link. CASE: This case focuses on the late postpartal manifestation of HG being associated with metastatic high-risk choriocarcinoma. Direct immunofluorescence was used to verify the diagnosis of HG. Symptomatic therapy with corticosteroids and antihistamines alleviated the pruritic symptoms associated with HG, but only the recurrent course of chemotherapy for the choriocarcinoma resulted in complete disappearance of all signs and symptoms of the HG. CONCLUSION: The time course of this case highlights once again the possible association of HG as a paraneoplastic syndrome of choriocarcinoma.

Fetal tissue Doppler echocardiography: detection rates of cardiac structures and quantitative assessment of the fetal heart.

OBJECTIVES: Tissue Doppler echocardiography (TDE) has been developed in adult cardiology, but only recently has it been applied to fetal heart studies. We implemented TDE on a high-resolution ultrasound system used for prenatal scanning by changing the Doppler settings, but without specific TDE equipment, to study cardiac tissue motion of normal fetuses in the second and third trimesters. METHODS: Using color Doppler settings optimized for low velocity motion assessment, detection rates of cardiac structures were measured in 47 fetuses. With pulsed Doppler, axial diastolic and systolic cardiac wall velocities were recorded in another 30 fetuses. RESULTS: In all fetuses TDE could detect cardiac wall motion. The right ventricular wall and the level of the atrioventricular valves were most easily seen. Axial contraction velocities of the fetal heart increased with gestational age. CONCLUSIONS: TDE can be used to study normal fetal cardiac function throughout gestation. A regular ultrasound system without additional hardware or software is suitable for screening studies using TDE.

[Role of estrogen receptor isoforms in the pathogenesis and treatment of endometrial cancer]. / Charakterisierung und Bedeutung verschiedener Ostrogenrezeptortypen unter besonderer Berücksichtigung des Endometriumkarzinoms.

Estrogens play a crucial role in the regulation of the physiology of breast tissue and endometrium. Furthermore, estrogen has been implicated in the initiation and progression of neoplasms of these tissues. Estrogens mediate their effects through various estrogen receptor isoforms and isotypes. In breast tissue and in the endometrium the classical estrogen receptor ERalpha represents the mainly expressed ER isoform, whereas in the ovary the alternative estrogen receptor ERbeta is predominantly expressed. This review briefly describes the structure, function and expression of these receptors with special regard to endometrial cancer. Recent data indicate that alterations of the physiological ERalpha/ERbeta ratio in endometrial cancer correlates with poor clinical outcome. The potential clinical relevance of differential ER-isotype expression is also discussed with respect to an antihormonal therapy.

The influence of hormones on CD44 expression in endometrial and breast carcinomas.

The expression of distinct variant isoforms of the cell surface glycoprotein CD44 (CD44v) has been found to be associated with metastatic potential of rodent adenocarcinoma cells and with an altered prognosis in several types of human cancer. In hormone-dependent gynecological cancers, different CD44v expression patterns have been observed. The influence of ovarian steroid hormones and their antagonists on CD44v expression is still unclear, since there are only retrospective correlation studies so far. Therefore, we examined the CD44 mRNA expression in a standardized stimulation experiment in a number of breast and endometrial carcinoma cell lines varying in estrogen receptor (ER) status. Higher CD44 overall expression was observed in ER positive endometrial and breast carcinoma cell lines when compared to corresponding ER negative cell lines. The number and composition of alternatively spliced isoforms showed no clear correlation to the ER expression status. Three CD44v isoforms were detected in all cell lines expressing CD44v, two of which have not been reported previously in normal endometrial cells. These isoforms may have specific functions in this type of carcinoma. In the second part of the study, the influence of (anti-) hormones on CD44 expression in endometrial carcinoma cell lines was examined. CD44 overall expression showed an increase when the cells were grown in medium containing fetal calf serum (FCS) as compared to cells maintained in medium-free of FCS. CD44 expression was transiently increased by estradiol (1 h). The CD44 splice pattern of endometrial cancer cell lines RL95-2 and Hec-1-A, after treatment with (anti-) hormones showed constant and high expression rates for distinct CD44v-isoforms such as CD44E (CD44v8-v10). Only certain weakly expressed isoforms changed their expression level during the experimental period, but no direct correlation to hormone treatment was observed. In conclusion, estradiol or FCS increase CD44 overall expression, but there seems to be no direct influence of ovarian steroid hormones on the CD44v splice machinery in endometrial carcinoma cell lines.

Hormone replacement therapy after treatment of breast cancer: effects on postmenopausal symptoms, bone mineral density and recurrence rates.

PURPOSE: Breast cancer (BC) is the most frequent female carcinoma and the major cause of death in women aged 35--50 years. The total number of patients surviving BC and especially the morbidity rate of patients below the age of 55 years has increased significantly in the last several years. As a consequence, the number of BC patients suffering from the long-term effects of estrogen deficiency due to adjuvant treatment is increasing. At present, hormone replacement therapy (HRT) following BC treatment is applied individually and mainly depends on the severity of postmenopausal symptoms (PMS) experienced by these patients. PATIENTS AND METHODS: In a retrospective study (total n = 185 BC patients, 64 with and 121 without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy and/ or (anti-) hormonotherapy] has been investigated. The surveillance period was up to 60 months. Evaluated were HRT effects on (1) PMS measured by a comprehensive life quality questionnaire, (2) bone mineral density (BMD) measured by osteodensitometry and (3) morbidity as well as mortality rates. RESULTS: Both groups did not differ with regard to tumor stage, lymph node involvement, metastasis, grading, and steroid hormone receptor status. A reduction in PMS was significant in women taking HRT (p < 0.001), especially in the subgroup of women < or =50 years (p < 0.0001). For both age groups, the median reduction in BMD (z-score) was less in women receiving HRT (< or =50 years: without HRT -1.99 vs. with HRT -0.95, p < 0.05; >50 years: without HRT -2.29 vs. with HRT -1.19, p < 0.01). There were no statistically significant differences regarding morbidity and mortality (p = 0.29). CONCLUSION: In this study of BC patients, the use of HRT shows positive effects on PMS and BMD. There was no significant influence on morbidity or mortality. However, a reevaluation of HRT in the routine management of BC patients should await the results of prospective randomized trials.