Recommendations for raloxifene use in daily clinical practice in the Swiss setting.

BACKGROUND/AIM: Raloxifene is the first selective estrogen receptor modulator that has been approved for the treatment and prevention of osteoporosis in postmenopausal women in Europe and in the US. Although raloxifene reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer, it is approved in that indication in the US but not in the EU. The aim was to characterize the clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene based on published scientific evidence to date. METHODS: Key individual patient characteristics relevant to the prescription of raloxifene in daily practice were defined by a board of Swiss experts in the fields of menopause and metabolic bone diseases and linked to published scientific evidence. Consensus was reached about translating these insights into daily practice. RESULTS: Through estrogen agonistic effects on bone, raloxifene reduces biochemical markers of bone turnover to premenopausal levels, increases bone mineral density (BMD) at the lumbar spine, proximal femur, and total body, and reduces vertebral fracture risk in women with osteopenia or osteoporosis with and without prevalent vertebral fracture. Through estrogen antagonistic effects on breast tissue, raloxifene reduces the risk of invasive estrogen-receptor positive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Finally, raloxifene increases the incidence of hot flushes, the risk of venous thromboembolic events, and the risk of fatal stroke in postmenopausal women at increased risk for coronary heart disease. Postmenopausal women in whom the use of raloxifene is considered can be categorized in a 2 × 2 matrix reflecting their bone status (osteopenic or osteoporotic based on their BMD T-score by dual energy X-ray absorptiometry) and their breast cancer risk (low or high based on the modified Gail model). Women at high risk of breast cancer should be considered for treatment with raloxifene. CONCLUSION: Postmenopausal women between 50 and 70 years of age without climacteric symptoms with either osteopenia or osteoporosis should be evaluated with regard to their breast cancer risk and considered for treatment with raloxifene within the framework of its contraindications and precautions.

Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients.

PURPOSE: To compare the prognostic impact of tumor angiogenesis factors (vascular endothelial growth factor [VEGF], angiogenin, and basic fibroblast growth factor [bFGF]), tumor proteolysis factors (urokinase-type plasminogen activator [uPA] and plasminogen activator inhibitor-1 [PAI-1]), and conventional tumor markers (stage, grade, and steroid receptors) in early breast cancer. PATIENTS AND METHODS: In the primary clinical study, tumor angiogenesis and other factors were detected in frozen biopsies from 305 primary breast tumors. VEGF expression was assessed by chemiluminescence immunosorbent assay (ICMA); angiogenin, bFGF, uPA, and PAI-1 by enzyme-linked immunosorbent assay (ELISA); and steroid receptors (estrogen receptor [ER] and progesterone receptor [PgR]) by enzyme immunoassay (EIA). In the validating clinical study, another set of 190 node-negative primary breast tumor samples were collected at a separate institution. RESULTS: Univariate analysis of the primary study showed that VEGF levels were positively correlated with recurrence (P < .001). Angiogenin levels were positively correlated with disease relapse (P < .005) for the overall collective group, but not within the node-negative subset. No significant correlations were found between tumor bFGF levels and patient survival. In multivariate regression analysis, the only independent predictors of relapse-free survival (RFS) were VEGF, uPA, and lymph node status. In the validation set, the distribution of VEGF and uPA values were similar to those in the primary study; low expression of both VEGF and uPA identified patients with a < or = 20% likelihood of recurrence within 7 years. CONCLUSION: Separate primary and validating clinical studies concur that tumor VEGF level is the most important prognostic parameter among several markers of tumor angiogenesis and proteolysis.

[Surveillance of hormone replacement therapy]. / Surveillance de l'hormonothérapie substitutive.

The prescription of hormone replacement therapy (HRT) requires a pretherapeutic evaluation and an ongoing surveillance during treatment. Pretherapeutic evaluation identifies the indications and contraindications to HRT. It includes a clinical examination, a Papanicolaou smear, and other tests according to the clinical situation. Monitoring of HRT consists of a first follow-up visit 3 months after beginning treatment to assess the effectiveness, side effects, and compliance with the therapy. Following this, yearly medical examinations should be scheduled. This paper describes the most frequent clinical signs that suggest a modification of treatment or the need to perform further investigations.

[Endometriosis]. / Endometriose.

Endometriosis is the female disease and very frequent. The grade differs widely: mildest stages, which do no harm, are occurring as well as severe manifestations destructing parts of the internal genital tract and creating adhesions. The etiology is still not unanimously clarified; there are probably etiologies more than one pathways. Endometrial particles which are capable of implantation can pass through the Fallopian tubes, lymphatic penetration, metaplastic processes or even immunologic deficiencies of macrophages have been accounted for the onset of endometriosis. The diagnostic procedure starts always with laparoscopic inspection. It is the beginning of a serious treatment. Classification is only possible after direct viewing of the pelvic organs. Staging and grading follows the proposal of the American Fertility Society, which is the standard even in non-English speaking areas of the world. The clinical symptoms of endometriosis are varying broadly. The leading symptom is [secondary] dysmenorrhoea. Treatment is managed by steps: I. Diagnostic endoscopic procedures with classification and removal of endometriotic foci so far possible. II. Pharmacologic therapy uses estrogen-progestogen combinations, progestogens, danatrol, GnRh-analogues, even tamoxifen and other regimens. III. Repetitive laparoscopy tries to completely clear from endometriotic remnants. Laparotomy was frequent in former times but is rarely carried out at present, however still mandatory in certain cases. The aim of treatment ist the cure of endometriosis and the reconstruction of a normal genital situation. Infertility is not a rare consequence particularly in severe cases according to stage IV AFS.

[Familial kidney agenesis: renal adysplasia as a cause of urogenital abnormalities in 3 generations]. / Familiäre Nierenagenesie: renale Adysplasie als Ursache urogenitaler Fehlbildungen in 3 Generationen.

Ultrasonographic investigations in a family with two members (uncle and niece) with bilateral renal agenesis disclosed various urogenital malformations (pelvic kidney, unilateral renal agenesis, duplication of kidneys and exstrophy of the cloaca). Pedigree and types of malformations found, focused on renal adysplasia, a condition caused by an autosomal dominant gene with incomplete penetrance and a wide range of expression. Carriers of the gene may reveal variable urogenital malformations, including uni- or bilateral renal agenesis of dysplasia, horseshoe kidneys, pelvic kidney and others. Prenatal ultrasonographic diagnosis is essential in pregnancies of potential or established carriers of the gene. In the present family, 2 subsequent pregnancies were subjected to ultrasonographic diagnosis; in one, fetal renal agenesis was detected and confirmed in the subsequently aborted fetus. Fetal ultrasonography with special attention paid to urogenital anomalies is indicated in any pregnancy of an established or potential carrier of the gene for renal adysplasia.

[Buserelin--a GnRh analog for the treatment of endometriosis]. / Buserelin--ein GnRh-Analogon zur Behandlung der Endometriose.

Within the scope of an open study, the results after treatment with Buserelin for patients with endometriosis is appraised. The patients are studied by laparoscopy or laparotomy before and after a six-month-long treatment. A clear decline of the endometriosis can be seen; however, endometriomas showed little or no reaction. The Buserelin therapy is shown to be well tolerated. It increases the rate of pregnancies, gives few biochemical complications and is an entirely acceptable therapy with few side effects. Buserelin offers a real alternative for the pharmacotherapy of endometriosis.

[Labor without prenatal care--an unnecessary challenge]. / Geburt ohne Schwangerschaftskontrolle--eine unnötige Herausforderung.

A group of 431 patients who had given birth, but had not attended regular check-ups during their pregnancy, are compared with a cumulative comparative group. The data is from a databank, belonging to the Swiss gynaecological working group. The following results are striking: Very young women, relatively older childbearing women, a noticeably high number of unmarried women and women from the Mediterranean countries. The number of women with heavy nicotine abuse is significant. The general progress of the pregnancy is however not noticeably different from the comparative group. The premature birth rate is higher in the group without pregnancy check-ups, as are birth deficiences and clinical foetal distress. Particularly noticeably is the high number of perinatal deaths. The pointlessness and the possible reasons for lack of regular pregnancy check-ups are discussed.

[PERGYN: perinatal-gynecologic information system]. / "PERGYN: Perinatologisch-Gynäkologisches Informationssystem".

PERGYN is a scientific research project of a purely medical nature. Its goal is to procure and evaluate the entire body of perinatal and gynaecological data in all its complexity. Data input is based on standardized medical concepts. Further details on the medical concept are stored in a course tree. In conjunction with the interview machine the course tree creates storable medical data. Data evaluation criteria are definable in dialogue on screen. Other medical areas can also be integrated into the data model. The conversion of medical constituents of the course tree calls for a process as "knowledge engineering".

[Obstetric-gynecologic data collection for quality control and responding to health and political status questions. A survey based on 250,000 patients]. / Geburtshilflich-gynäkologische Datenerhebung zur Qualitätskontrolle und Beantwortung gesundheits- und standespolitischer Fragen. Eine Bestandsaufnahme nach 250,000 Patientinnen.

Since January 1, 1983 a total of 250,000 patient records have been stored in computer-compatible form in the data base of the Working Group of Swiss Gynecologic Clinics (59 gynecologic-obstetric departments). The information resulting from this mass of data is commented on and analyzed in concise form. Problems of quality control, health care and status-related policies can be addressed and resolved on the basis of up-to-date data which are always available. In the authors' experience, the benefit of correctly compiled statistics is indisputable.

[Uterus didelphys and vagina duplex with pregnancy to full term]. / Uterus didelphys et vagina duplex mit ausgetragener Schwangerschaft.

Report on a case of uterus didelphys and vagina duplex in which the fetus was carried to full term. The importance of this anomaly with regard to fertility and various problems in the course of pregnancy are discussed.

[Laparoscopy in gynecology and obstetrics]. / Die Laparoskopie in Gynäkologie und Geburtshilfe.

Thanks to the statistics of the Arbeitsgemeinschaft Schweizerischer Frauenkliniken (Swiss Gynecological Clinics' Working Group) it has for the first time become possible to report on larger numbers of laparoscopies performed in Switzerland. In contrast to most international statistical records, data relating to this subject are gathered prospectively; there is no doubt that this improves the quality of the data. The authors report on a total of 18,186 laparoscopies performed in 1983/84/85, in 50% of the cases for sterilization. The various sterilization methods employed are discussed. As far as diagnostic laparoscopies are concerned, the indications and techniques are described. Serious intraoperative complications occurred in 15 cases, which corresponds to one serious complication in every 1,212 laparoscopies. Fortunately, not a single patient died as a direct result of the laparoscopy. The results are compared with those in the international literature. With regard to late-onset morbidity it is evident that there are more complications with the more complex procedure of diagnostic laparoscopy.

[Treatment of urinary tract infections with SolcoUrovac]. / Harnwegsinfektbehandlung mit SolcoUrovac.

Urinary tract infections are among the most common infections found in women. If recurrences or reinfections become frequent treatment can be problematic. Immunisation of the patients by vaccinating them against urinary tract pathogens offers a possibility of managing these infections. In clinical trials we tested SolcoUrovac, a new vaccine to counteract bacterial pathogens, with regard to efficacy, frequency of recurrence, and tolerance. 113 of the 118 patients included in this study with bacteriuria (urine culture germ count greater than or equal to 10(5)/ml), had acute cystitis. 47 of these patients had recurring urinary tract infections. Follow-up examinations were conducted after 2, 3, 4, 5, 6 and 12 months. A urine culture assay was performed during each examination, as well as a relevant bacterial differentiation test and a urine sediment evaluation. Two to six weeks after termination of the vaccination series 72.6% of the patients were largely free from signs and symptoms. The rate of recurrence/reinfection dropped from 2.5 to 0.24 infections for a period of 12 months. After one year, 94 of the patients (80%) were still free from reinfection.

[Gynecologic cancers: preventive examinations and their limits. An analysis of the current staging and percentage distribution based on 2,612 cancers of the 1 January 1983 to 25 November 1985 cumulative statistics of the Society of Swiss Gynecologic Clinics]. / Die gynäkologischen Karzinome: Die Vorsorgeuntersuchungen und ihre Grenzen. Eine Analyse der aktuellen Stadieneinteilung und prozentualen Verteilung zu- und untereinander anhand von 2612 Karzinomen aus der seit 1. 1. 1983 bis 25. 11. 1985 kumulierten Statistik der Arbeitsgemeinschaft Schweizerischer Frauenkliniken.

An overview of the stages and age distributions is given for 2612 invasive genital and 1237 breast cancer cases, called from the data bank, compiled by the Swiss working group of the departments of gynaecology and obstetrics and consisting of 172,399 cases (1983-1985). The general over-representation of advanced and more therapy-resistant cancer stages (exception: corpus cancer) and their high incidence in advanced menopausal age, still characterise the present, all but satisfactory condition. Progress in the treatment of genital and breast cancers can be achieved only through improved early diagnosis with preventive examinations, without a limitation placed on age.

[Prenatal ultrasonic diagnosis of severe congenital microcephaly]. / Antenatale Ultraschall-Diagnostik schwerer kongenitaler Mikrozephalie.

Antenatal ultrasound diagnosis of isolated microcephaly is difficult. Over and above this, other malformations must be safely excluded. Infants with congenital microcephaly are mentally and motorially severely retarded. Basing on two case reports with four microcephalic foetuses, the antenatal problems of sonographic diagnosis are explained. In all cases there was an isolated microcephaly without other malformations. Sonographic examination enabled early detection of three microcephalic foetuses between the 15th and 32nd week of gestation, and pregnancy could be terminated prematurely. Spontaneous delivery occurred in one pregnant woman at term; sonography had not been employed in this case.