Ovarian cancer is chemosensitive, but most patients with advanced disease die from tumor progression. As 25% of the patients can be cured by chemotherapy, it is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients with untreated ovarian cancer were entered in a multicenter phase I/II trial of multicycle HDCT. Median age was 46 (19–59 years); International Federation of Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual disease >1 cm after surgery. Two courses of induction/mobilization therapy with cyclophosphamide (250 mg/m2) and paclitaxel (250 mg/m2) were used to collect peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area under curve (AUC) 18–22) and paclitaxel followed by one course of carboplatin and melphalan (140 mg/m2) with or without etoposide (1600 mg/m2). Main toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating etoposide resulted in manageable toxicity (69% without grade 3/4 toxicity). One patient died from treatment-related pneumonitis. At 8 years median follow-up, median progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0 months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a multicenter setting. A European phase III trial based on this regimen is evaluating the efficacy of HDCT.

BACKGROUND:Granulosa cell tumor of the ovary is an uncommon neoplasm. The majority of patients are diagnosed in early stages of disease and overall prognosis is favorable. The stage at time of diagnosis is the only prognostic factor that is unequivocally related to survival. Other prognostic factors have not been well defined and are discussed in the literature controversially.MATERIALS AND METHODS:In a multi-institutional retrospective study we analyzed all relevant clinical data of patients with histologically proven granulosa cell tumor of the ovary. We applied the Kaplan-Meier method in order to estimate overall survival rates and evaluate prognostic factors.RESULTS:The median follow-up was 75 months (range, 6-315 months). Overall survival was 87% and 76% after 5 and 10 years, respectively. Eighty percent of granulosa cell tumors were diagnosed stage I (FIGO). The survival rate after recurrence was 56.8% after 10 years. Mitotic rate (p=0.003), tumor stage (p<0.001) and residual tumor disease (p<0.001) were associated with a poor prognosis (p<0.001). Age and rupture of the tumor could not be confirmed to be of prognostic value.CONCLUSION:The results of our study showed that the mitotic index may be a valuable prognostic factor. Complete tumor resection should always be attempted, since residual tumor disease is associated with a poor prognosis. Prospective studies are needed in order to confirm our findings.

International Journal of Gynecology & ObstetricsVolume 70, Issue S1 p. A84-A84 Breast Menstrual timing of breast cancer surgery A. Haeen, A. HaeenSearch for more papers by this authorW.J.M. Hrushesky, W.J.M. HrusheskySearch for more papers by this authorA. Ebert, A. EbertSearch for more papers by this authorF. Opri, F. OpriSearch for more papers by this authorH. Weitzel, H. WeitzelSearch for more papers by this author A. Haeen, A. HaeenSearch for more papers by this authorW.J.M. Hrushesky, W.J.M. HrusheskySearch for more papers by this authorA. Ebert, A. EbertSearch for more papers by this authorF. Opri, F. OpriSearch for more papers by this authorH. Weitzel, H. WeitzelSearch for more papers by this author First published: 09 December 2003 https://doi.org/10.1016/S0020-7292(00)82768-XAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume70, IssueS12000Pages A84-A84 RelatedInformation

Die Kombination von Cisplatin und Paclitaxel erwies sich in zwei randomisierten Pha- se-III-Studien gegenüber dem älteren Standard (Platin plus einem Alkylans) überlegen [1,2] und wurde deshalb als neuer Standard in der Primärtherapie des fortgeschrittenen Ovarialkarzinoms akzeptiert. Die besseren Resultate wurden mit mehr Toxizität, speziell Neurotoxizität, erkauft. Die Substitution von Cisplatin durch Carboplatin sollte den Effektivitätsvorteil dieser neuen Kombination mit einem günstigeren Toxizitätsprofil verbinden. 7 Phase-I/II-Studien entwickelten eine Kombination von Carboplatin-Paclitaxel [3,4, 5,6,7,8,9]; die Erfahrungen dieser Studien führten zur Initiierung von 3 Pha- se-III-Studien zum Vergleich der Cisplatin-Paclitaxel-Standardtherapie mit einer Carbo- platin-Paclitaxel-Kombination. Die Interimsanalyse der AGO-Studie OVAR-3 [10] wird hier vorgestellt. Zwischen 10/95 und 11/97 wurden 798 Patientinnen in diese prospektiv randomisierte Studie eingeschlossen. Die Therapiearme bestanden aus Carboplatin dosiert nach AUC 6 [11] plus Paclitaxel 185 mg/m2 (Arm A) und Cisplatin 75 mg/m2 plus Paclitaxel 185 mg/m2 (Arm B). Paclitaxel wurde als 3-Stunden-Infusion verabreicht, die Prämedikation bestand aus einer Einmaldosis von Dexamethason, einem 5-HT3-, einem H1 und einem H2-Antagonisten. In beiden Armen wurden 6 Zyklen alle 3 Wochen verabreicht. 790 der 798 rekrutierten Patientinnen erfüllten die Einschlußkriterien mit einem Ovarialkarzinom FIGO IIB-IV und einem Intervall ≤ 6 Wochen zur Primäroperation.

The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c- erbB-2 . Its overexpression, occurring in approximately one-third of all breast carcinomas, is associated with a poor prognosis. A humanized mouse antibody against HER2 has been developed by genetic engineering. Here an unspecific human IgG was connected to the recognizing mouse IgG fragment. The allergization typical for allogeneic antibodies does not take place in this context. The effectiveness of this antibody has been confirmed by two international prospective phase III trials that tested it alone and combined with chemotherapy. Both modes of application increased the response rates and the time to progression. Side-effects were rare except for a high rate of cardiac dysfunction when the antibody was combined with anthracyclines. The effectiveness and negligible side-effects of the chimeric antibody against HER2 (Herceptin) render it a valuable tool in the treatment of breast cancer.

The standard treatment for ovarian cancer consists of staging laparotomy with aggressive debulking, a pelvic and paraaortal lymphadenectomy if indicated and a postoperative chemotherapy. A reappraisal of primary high dose chemotherapy in advanced ovarian cancer seems warranted because of high remission rates of such schedules in palliative situations. For a nation-wide interdisciplinary phase I/II multi-center-study 49 patients were recruited. Induction for stem cell mobilization consists of two cycles of cyclophosphamide and taxol. Three high dose cycles follow with a steady dose-escalation of carboplatin by a factor of 4, this is contrast to a conventionally dosed chemotherapy. During the first two cycles taxol is added, during the third etoposide and melphalane. The plan of primary sequential high dose therapy proved feasible in this study. In a prospective randomized follow-up study primary high dose therapy is compared to conventional chemotherapy (AGO-Ovar-5-study). It results will answer the question whether primary high dose chemotherapy with stem cell support improves the course of ovarian cancer compared to conventional treatment.

We present a case of congenital cystic adenomatoid malformation of the lung (CCAM) diagnosed at 23 weeks of gestation with concomitant fetal hydrops. The sonographical picture of CCAM disappeared in the third trimester of pregnancy and fetal hydrops resolved under medication with digitalis to the mother. The neonate showed mild dyspnea; the prenatal diagnosis of CCAM was confirmed by chest X-ray and computed tomography. The affected lung segments were dissected at 5 days of age. The diagnosis of CCAM type III was confirmed histologically.

The transfer of cytokines through human fetal membranes after the development of intra-amniotic infection could be important in the immune response to such infections and in processes leading to rupture of the membranes and premature delivery. We investigated the transfer of I-125-labelled IL-8, a key component of the immune response, through human fetal membranes after section and vaginal deliveries in an in vitro culture system. Radioactivity was added to both sides of the membranes, and transfer of radioactivity calculated as percentage of that added at 4, 7 and 24 h. The integrity of the cytokine was measured after 24 h. Between 15 and 20% of the added radioactive cytokine was found intact on the opposite side of the membrane after 24 h. The percentage of transferred IL-8 after 24 h was only marginally affected by the side to which it was added and by labour. These data show for the first time that IL-8 can be transferred in both directions through human fetal membranes in vitro. (C) 1998 Chapman & Hall Ltd.

Background: Paclitaxel is active in the treatment of patients with metastatic breast cancer (MBC). Preclinical studies showed additive cytotoxicity and non-overlapping toxicity of paclitaxel and 5-fluorouracil (5-FU). Patients and Methods: Pretreated patients with MBC received paclitaxel (3 h i.v.) starting with 125 mg/m(2) and escalating the dose by 25 mg/m(2) steps per dose level up to 200 mg/m(2), followed by a fixed dose of 1,200 mg/m(2) 5-FU (24 h i.v.). Objectives were to determine the maximum tolerated dose (MTD) of paclitaxel and to evaluate the efficacy and safety of this combination. Results: 22 patients entered this trial. For safety analysis 93 treatment cycles were evaluable. The main toxicity was hematological: neutropenia WHO 3+4: 15.0% of cycles, thrombocytopenia WHO 3+4: 4.3% of cycles. Major non hematological toxicities were rare and mostly of WHO grade 1 or 2. Four patients with partial response (response rate 20%) and 8 patients with stable disease were observed. Median time until progression was 13.1 weeks (range 2.3-94.6 weeks). Conclusions: This study indicates a moderate efficacy and good tolerability of paclitaxel in combination with 5-FU in patients with MBC. The MTD of paclitaxel in this combination has not been reached.

Multivisceral resectioning is the only curative treatment for progressive carcinomas extending beyond the organ. The results of 25 consecutively operated patients are presented in this prospective observational study. Twelve patients underwent surgery for a primary tumor and 13 for a recurrence. Radical resectioning was achieved in 5 of 12 and in 3 of 13 patients. Restoration of continuity obtained in 11 of 12 and in 7 of 13 patients. Morbidity was 33% and 62%. None of the patients died from complications. An aggressive surgical approach is justifiable on account of the acceptable morbidity and mortality as well as the high rate of preserved continence through modern reconstruction procedures.

Einführung: Phylloide Tumoren, auch Cystosarcoma phylloides (CSP) genannt, sind seltene fibroepitheliale Tumoren, deren Inzidenz 0.3- 1.0% aller Neoplasien der Brust beträgt. Die Behandlung des CSP wird in der Literatur kontrovers diskutiert. Die vorliegende Untersuchung stellt aktuelle Erfahrungen in Diagnose, therapeutischem Vorgehen und klinischer Nachsorge; vor.

The diagnosis of a premature rupture of membranes presents no problem in the vast majority of cases. However, a reliable diagnosis is clinically not possible in about 10%. Most methods available lack the necessary sensitivity and specificity. Since the clinical consequences of a false diagnosis are considerable (overtreatment for false-positive and risk of infection for false-negative results), it is essential to clinically establish new, minimally invasive methods with higher predictive powers. In the present study we compared: the AMNI Check for detection of insulin-like growth-factor binding protein 1 (IGFBP-1); a membrane immunoassay for detection of fetal fibronectin (fFn); pH indicator paper; and, to verify a rupture of membranes in unclear cases, amniocentesis with installation of indigo carmine. The examination was performed in a group of 75 patients, 35 with and 40 without rupture of the membranes. The best results were obtained for the AMNI Check (sensitivity and negative correctness 100%, specificity and positive correctness 83%). With the same sensitivity and negative correctness, the membrane immunoassay for fFn achieved a specificity of 70% and a positive correctness of 74%. The pH indicator paper had the lowest predictive value (sensitivity 94%, negative correctness 93%, specificity 63%, positive correctness 69%). Both the AMNI Check and the test for detection of fetal fibronectin can be recommended for reliable exclusion of premature rupture of membranes. Amniocentesis should however be performed in uncertain cases with a positive test result. Nevertheless, considerable reduction of this invasive method is possible.