Search

Goals of Work: The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries., Patients and Methods: This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs., Main Results: A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living., Conclusions: CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.

Our objective was to determine pretreatment factors with an independent impact on survival after adjusting for response to preoperative chemotherapy and to describe parameters predictive for achieving a pathological complete remission (pCR) after preoperative chemotherapy containing an anthracycline. We performed univariate and multivariate analyses to describe the impact of the following pretreatment characteristics of 240 primary breast cancer patients who received preoperative chemotherapy containing an anthracycline at our institution on disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS): age, stage, clinical tumor size, clinical nodal status, grading, and expression of estrogen receptor, progesterone receptor, Her2/neu, Ki67, Bcl-2 and p53. Afterwards, the response to preoperative chemotherapy was added to the multivariate model in order to evaluate which pretreatment parameters retained their prognostic impact. In addition, univariate analysis was performed to describe pretreatment variables predictive for achieving a pCR. With a median follow-up of 6.4 years (range 0-10.4), only grading retained its independent impact on DFS, DDFS and OS [hazard ratio (HR) 1.5, 1.7 and 2.9, respectively; p<0.05] after adjusting for the strongest independent prognostic factors pathological T category at surgery (HR 1.6, 1.8 and 1.7, respectively; p<0.001) and pathological N category at surgery (HR 2.3, 2.4 and 2.1, respectively; p<0.001). Predictive factors for the achievement of pCR (p<0.05) were age under 35 years, lower stage or smaller clinical tumor size and higher expression of Bcl-2 at diagnosis. We conclude that only grading retained its independent prognostic impact on DFS, DDFS and OS after adjusting for pathological response of breast tumor and axillary lymph node metastases to preoperative chemotherapy. According to our data, it could be hypothesized that young patients with early tumor stage and small primary tumors might profit most from preoperative chemotherapy.

Objective: A retrospective comparison of the efficacy and toxicity of docetaxel and paclitaxel in the treatment of metastatic breast cancer (MBC) was conducted based on our institution's experience since 1992., Methods: Two groups of 43 patients who received a similar chemotherapy regimen containing either docetaxel or paclitaxel were matched for the number of prior treatments., Results: Toxicity was mild in both groups. Tumour growth control, defined as either objective response or stable disease for at least 6 months, was obtained in a significantly higher proportion of patients treated with docetaxel compared with paclitaxel (67 % vs. 44 %, p = 0.001). Moreover, fewer patients progressed during treatment with docetaxel (28 % vs. 53 %, p < 0.001). At a median follow-up of 17 months there was no significant difference between the groups in median progression-free survival (7 vs. 5 months, p = 0.123) or median overall survival (OS) (12 vs. 11 months, p = 0.211). According to the method of Kaplan and Meier estimated OS rates at 1 year (74 % vs. 62 %) and 2 years (50 % vs. 26 %), however, were in favour of docetaxel. In a multivariate analysis only a positive hormone receptor status was significantly associated with improved OS., Conclusion: These results suggest that docetaxel may be superior to paclitaxel in the treatment of MBC.

Stem cell-supported high-dose chemotherapy (HDCT) is currently being evaluated in patients with high-risk primary breast cancer (HRPBC), as defined by extensive axillary lymph node involvement. Conclusive results from randomized studies with sufficient patient numbers and follow-up are pending. We retrospectively analyzed 144 HRPBC patients enrolled in a single-arm trial of tandem HDCT at the University of Heidelberg to evaluate the prognostic value of nodal ratio, HER2/neu status, and cytokeratin-positive bone marrow cells and to compare the outcomes of these patients with those of a conventionally treated control group of 91 patients matched by nodal ratio, tumor size, combined hormone-receptor status, and HER2/neu status. The tandem HDCT regimen consisted of 2 cycles of induction chemotherapy followed by 2 cycles of blood stem cell-supported high-dose ifosfamide, 12 g/m2; carboplatin, 900 mg/M2; and epirubicin, 180 mg/m2. Conventionally treated patients received a regimen containing anthracycline without taxanes (52 patients) or CMF (cyclophosphamide, methotrexate, and 5-flurouracil; 39 patients). With a median follow-up of 3.8 years, disease-free, distant disease-free, and overall survival rates were 62%, 65%, and 84%, respectively. In univariate analysis, besides the hormone receptor status (P = .007), HER2/neu overexpression was the strongest predictor of earlier death (P = .017). In multivariate analysis, a nodal ratio of > or =0.8 was found to be the only independent predictor of relapse (relative risk [RR] = 2.09; 95% confidence interval [CI], 1.21-3.60; P = .008) and only the absence of hormone receptors was associated with earlier death (RR = 3.59; 95% CI, 1.45-8.86; P = .006). Despite a trend toward later distant relapse after HDCT compared with standard-dose chemotherapy with a median follow-up of 3 years (P = .059), thus far, matched-pair analysis has not demonstrated significantly better survival rates after HDCT in all matched patients (P = .786) or in the subgroups of anthracycline-treated patients and patients with and without overexpression of HER2/neu. So far, the follow-up time has been too short to draw definite conclusions; however, patients with a nodal ratio of > or =0.8, receptor-negative tumors, or HER2/neu overexpression are at high risk for relapse and death, irrespective of the kind of adjuvant chemotherapy.

On the assumption that the architecture of blood vessels of malignant tumors, formed by neoangiogenesis, shows characteristics that are different from those of blood vessels of benign tumors or physiological findings, we have tried in the present study to investigate the behavior of these different vessels under increased blood pressure. Using a special stand, the same sonographic section could be stably maintained during an examination time of approx. 4 minutes. Using a new computer program, the color pixels of the employed Angio color technique were quantified and recorded as a function of the measured blood pressure. To increase blood pressure, the patient had to press a hand grip, which practically always caused a systolic blood pressure elevation of more than 15-20 mmHg. Seventy patients with sonographically detected breast tumors were examined; 54 (14 benign and 40 malignant tumors) could be included in the evaluation. We found four typical types of curves: Curve type 1 is associated with an instantaneous increase in blood flow with increased blood pressure, followed by a drop in the blood pressure, with a slow decrease in blood flow as the blood pressure drops (with 29 malignant and 3 benign tumors). Curve type 2 shows a continuous increase in blood flow-though somewhat delayed with respect to the rise in blood pressure-which is also observed when the blood pressure drops (exclusively benign tumors). In curve type 3, maximum blood flow is reached after the blood pressure maximum, and then the blood flow decreases (1 benign and 3 malignant tumors). Curve type 4 features decreased blood flow in spite of increased blood pressure (3 benign and 5 malignant tumors). The described quantification method, in combination with the stand, permits for the first time analysis of a tumor under increased blood pressure as to its blood flow behavior over time in an examination using a challenge test. Here one can find two distinctive curve types (types 1 and 2) that correlate mostly with malignant (type 1) or benign (type 2) breast tumors. Should this tendency be substantiated by additional large-scale studies, it would seem that a new ultrasonic possibility for differential diagnosis has been found.

To establish the requirements for real-time transfer of an ultrasound examination via telecommunication network the following tests were performed: The ultrasound data were transferred from the video out of an ultrasound system to a basis terminal of the German Telekom. Simultaneously, an external video camera filmed the positioning and movements of the ultrasound transducer, and the verbal comments were recorded. These informations were transmitted to Karlsruhe and London, where they were rerouted to the examination room in Heidelberg. Here the informations were received on a Telecom reception unit/terminal and compared directly with the initial signal. The quality was sufficient if the moving ultrasound images and the camera image of the transducer as well as the oral comment were transmitted over 2 parallel ISDN lines. The delay to a real-time transmission of the examination process is only in the range of milliseconds. If only one ISDN line is used, the image quality is unsatisfactory, three parallel lines do not bring significant improvement of image quality. Telemedicine seems a new possibility to bring the knowledge of specialized centers to the practicing gynaecologists thus avoiding unnecessary referrals. Still unanswered, however, are the problem of liability, data protection and costs.

The association of increased maternal serum alpha-fetoprotein levels (MS-AFP) with certain morphologic anomalies of the fetus is fully established. These anomalies are abdominal wall defects (e.g. omphalocele, gastroschisis, complete eventration), neural tube defects (anencephalus, spina bifida, encepalocele) and other malformations (e.g. coccygeal teratoma). The present study compares MS-AFP levels with amniotic fluid alpha-fetoprotein (AF-AFP) and acetylcholinesterase activity, the results of ultrasound, genetic and morphologic examination. Between April 1992 and November 1995 60 patients were referred to our clinic for further diagnosis after detection of elevated MS-AFP. After an ultrasound examination was carried out amniocentesis (AC) was performed in 54 cases, AC + placentesis (PC) in 3 patients and PC only in 3 cases with anhydramnion. Mean maternal age was 29 years (range 20-37 years). Punction was performed at a median of 19 + 1 weeks of gestation (15 + 2-23 + 2 weeks of gestation). MS-AFP, AF-AFP and acetylcholinesterase activity was measured. MS-AFP and AF-AFP were given as multiples of the median (MoM). Values < or = 1-2.0 MoM were considered normal. Elevated levels were defined to be greater than 2 MoM. In all cases the chromosomal finding was normal or norm variant. Sonographical anomalies were detected in 7 fetuses (3 cases with spina bifida, 1 case with omphalocele and 3 cases with abdominal wall defects in connection with other malformations). All sonographic diagnoses were confirmed post partum. The MS-AFP varied between 0.9-6.0 MoM. In 7 cases MS-AFP previously (referring center) evaluated as increased was found to be within normal range in our department. This cases included normal values were found in 30 cases and 25 findings were pathological. 2 out of 7 structurally abnormal fetuses had normal values, 5 of them had elevated MS-AFP. In the group of normal fetuses the highest MS-AFP we found was 6.6 MoM. In the AC-group the AF-AFP ranged between 0.7-8.7 MoM, it was within normal range in 50 and pathological in 8 cases. In the group of fetuses without structural anomalies the highest AF-AFP was 7.5 MoM. In the group of fetuses with structural anomalies the AF-AFP values were 1x normal and 3x pathological (> 3.5 MoM). Acetylcholinesterase activity in the amniotic fluid was negative in 51 cases, positive in 4 cases and faint positive in 2 cases. In all fetuses with structural anomalies in which an AC could be performed, acetylcholinesterase activity was positive. On the other hand we found only 1 of the structurally normal fetuses with positive acetylcholinesterase activity. Elevated MS-AFP and AF-AFP may be an indicator for morphological anomalies. Yet there were many positive results without any sonographical findings. The determination of a positive acetylcholinesterase activity in the amniotic fluid is more specific. All malformations have been detected by ultrasound examination before the results of the AF-AFP were available.

Sonographic examinations of the female mammary gland within the frameworks of the diagnosis of breast cancer playa fundamental role in the early detection of benign and, in particular, of malignant growths. Sonographic blood flow determinations can be used as an auxiliary noninvasive examination method. This is based on the fact that malignomas differ from benign tumors in that they display a pathological increase in vascular-ization. These changes of the circulatory conditions can be utilized in the diagnosis of the dignity of breast cancer.

The present study was undertaken to evaluate the correlation of the favorable in vitro characteristics of the anti-mucin Mabs 12H12 and BM-7 with high tumor accumulation in vivo. They were labeled with 99mTc; their biodistribution in nude mice bearing mammary tumor xenograft AR was examined and immunoscintigraphy was performed after 24 h. 99mTc-labeling of the Mabs 12H12 and BM-7 led to tumor uptakes of 20.7% and 8.8% ID/g, respectively, after 48 h. Tumor-to-muscle ratios were 31 (12H12) and 18 (BM-7). Tumor xenografts were clearly visualized in immunoscintigrams. Combination of Mab 12H12 and 99mTc provides high tumor-to-tissue ratios shortly after administration.