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G Bastert

Publications and source records attributed to G Bastert.

At least 37 records · Page 2Linked to original sources

[DNA cytometry in breast carcinoma. Review of method and value in assessing prognosis].

DNA flow cytometry (FCM) has become a routine method in breast cancer diagnosis for evaluation of ploidy and proliferation kinetics (cell cycle analysis). Image cytometry is less practicable and provides less information than flow cytometry. An optimized technique with a low coefficient of variation is required for optimal results in flow cytometry. The S-phase fraction and the proliferation index (sum of S-phase fraction and G2M fraction) provide prognostic and therapeutically relevant information. A profound knowledge of the technique and its limitations is indispensable for the interpretation of FCM results. It remains to be established whether immunohistological evaluation of cell proliferation has the same prognostic value. Future developments are to be expected from multiparametric analysis and the improvement of mathematical analysis of FCM measurements.

Breast

[Subtyping and prognostic assessment of invasive lobular breast carcinoma].

Invasive lobular carcinoma (ILC) is recognized in its classical form and as variants with tubulo-lobular, solid, pleomorphic, alveolar or signet ring cell differentiation. The most common classical form differs from invasive ductal carcinoma (IDC) by its slower tumor proliferation and less common axillary metastases. When compared stage by stage, long term prognosis is similar to IDC, however. Prognostic subtyping of ILC can be achieved by the recognition of variant forms and mitotic counting. The combination of these factors may be used for tumor grading (5-year survival 100% with grade 1 vs. 82% with grade 2, and 57% with grade 3, n = 241). The detailed histopathologic diagnosis therefore permits prognostic assessment also in ILC.

Adult

Sonographic blood flow measurements in malignant breast tumors. A potential new prognostic factor.

BACKGROUND: The aim of this study was to find a possible relationship between the biological behavior of carcinomas of the breast and sonographically detectable blood flow after first studies showed a correlation between blood flow and prognostic factors. METHOD: 259 patients with ductal invasive breast cancer were examined using MEM (i.e., the Maximum Entropy Method), a new sonographic blood flow measurement technique capable of discerning considerably slower blood flow velocities than Doppler sonography. Due to the lack of objective methods for quantifying the blood flow, the findings were divided into three classes dependent upon the visual color information obtained. The blood flow was correlated with the size of the tumor, lymph node and receptor status, ploidy and S-phase fraction. RESULTS: Most of the patients with small tumors, without lymph node metastases, with positive receptors, with a diploid genome, and with a low S-phase fraction belonged to the group with the lowest blood flow. CONCLUSION: The close relationship between the established prognostic factors and the sonographic blood flow measurements using MEM might be indicative of a new preoperative prognostic factor; this must, however, be confirmed by larger studies.

Blood Flow Velocity

Tandem high-dose therapy with ifosfamide, epirubicin, carboplatin and peripheral blood stem cell support is an effective adjuvant treatment for high-risk primary breast cancer.

We evaluated the therapeutic efficacy and toxicity of a tandem high-dose therapy with peripheral blood stem cell (PBSC) support in 40 patients with high-risk, primary breast cancer (stage II-III) and involvement of ten or more positive axillary lymph nodes. Their median age was 44 years (range 23-56). Two cycles of cytotoxic chemotherapy with ifosfamide (10000 mg/m2) and epirubicin (100 mg/m2) were administered. Granulocyte colony-stimulating factor (G-CSF) was given to hasten neutrophil reconstitution and to mobilise PBSC during marrow recovery. Leukaphereses were performed following the first and/or second cycle. Tandem high-dose therapy consisted of two cycles with ifosfamide (15 or 12 g/m2) and epirubicin (150 mg/m2), while carboplatin (900 mg/m2) was added for the last 24 patients included. Using an immunocytochemical method, two of 11 patients had cytokeratin-positive tumour cells in three leukapheresis products that were collected following the first G-CSF-supported cycle with ifosfamide and epirubicin, whereas only two harvests obtained following the second cycle in 26 patients contained cytokeratin-positive tumour cells. The number of CD34+ cells/kg re-infused following both high-dose cycles was similar (4.20 +/- 0.29 x 10(6), first cycle and 5.25 +/- 0.63 x 10(6), second cycle), and no notable difference was noted in the speed of haematological reconstitution. An absolute neutrophil count (ANC) of 0.5 x 10(9)/1 was reached after a median time of 13 days, while an unsupported platelet count of 20.0 x 10(9)/1 was achieved after a median time of 8 (first cycle) and 9 (second cycle) days post-transplantation. Patients autografted with more than 7.5 x 10(6) CD34+ cells/kg had platelet counts above 20 x 10(9)/1 within less than 10 days. 6 patients relapsed between 7 and 11 months (median 8 months) post-transplantation. 37 patients are alive and in remission with a median follow-up time of 11 months (range 1-38). This translates into a probability of disease-free survival (DFS) of 77% (95% CI 32-95%) at 38 months. The probability of overall survival is 85%, since 3 patients with local relapse achieved a second complete remission following surgery and involved-field radiotherapy. In conclusion, a sequential high-dose therapy including ifosfamide, epirubicin, carboplatin and PBSC support is well tolerated and effective in patients with high-risk primary breast cancer. Involved-field irradiation should be performed post-transplantation to reduce the risk of local relapse.

Adult

Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer.

Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases.

Antibodies, Monoclonal

Carbon dioxide laser tissue welding: an alternative technique for tubal anastomosis?

Microsurgical tubal anastomosis is the gold standard for treatment of tubal occlusion. The present study was performed to establish the feasibility of tubal anastomosis by welding tissue with a defocused CO2-laser beam during laparotomy and with an endoscope. In an animal experiment, 70 white New Zealand rabbits were randomized in 2 study groups (E1, E2) and 3 control groups (C1, C2, C3) as follows: C1, 10 animals, no operation, as controls for the efficiency of the insemination technique; C2, 5 animals, spontaneous healing after tubal segment resection, to quantify spontaneous recanalization of the tube; C3, 15 animals, microsurgical end-to-end adaption after tubal segment resection; E1, 20 animals, laser welded anastomosis after segment resection via laparotomy; E2, 20 animals, laparoscopic laser welded anastomosis after segment resection. The pregnancy rate in C1 was 80%. None of the animals in C2 but 60% of the rabbits in C3 conceived. After sutureless anastomosis by laser welding 50% of the laparotomized, and 40% of the laparoscopically operated group became pregnant. Morphological examination of the oviducts after relaparotomy showed comparable patency rates of 70% in C3, 70% in E1, and 65% in E2. Whereas no dehiscence of anastomoses was observed in C3, 20% of the welded tubes in E1 and 22.5% in E2 were dehiscent. Tubal anastomosis took approximately three times as long laparoscopically as during laparotomy. Thus, laser welding as a sutureless alternative technique of tubal anastomosis should be viewed critically. A reduction of sutures through laser-assisted anastomosis might, however, be considered.

Anastomosis, Surgical

Low frequency of BRCA1 germline mutations in 45 German breast/ovarian cancer families.

In this study we investigated 45 German breast/ovarian cancer families for germline mutations in the BRCA1 gene. We identified four germline mutations in three breast cancer families and in one breast-ovarian cancer family. among these were one frameshift mutation, one nonsense mutation, one novel splice site mutation, and one missense mutation. The missense mutation was also found in 2.8% of the general population, suggesting that it is not disease associated. The average age of disease onset in those families harbouring causative mutations was between 32.3 and 37.4 years, whereas the family harbouring the missense mutation had an average age of onset of 51.2 years. These findings show that BRCA1 is implicated in a small fraction of breast/ovarian cancer families suggesting the involvement of another susceptibility gene(s).

Adult

Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer.

PURPOSE: We investigated quality and efficacy criteria of an autologous, physically and immunologically purified, Newcastle disease virus (NDV)-modified, irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a through c) of patients vaccinated between 1991 and 1995. MATERIALS AND METHODS: Included were 63 patients with primary breast cancer (a), 27 with metastatic pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy as supportive treatment. After cryoconservation and purification, the vaccines varied in applied numbers of viable cells and dead cell contaminations. We retrospectively hypothesized that an immunogenic vaccine should contain at least 1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort was thus divided into two groups; one that received vaccine type A (A), fulfilling both criteria; and the other type B (B), missing one or both criteria. RESULTS: Conventional prognostic factors were wall balanced between A and B in cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and disease-free survival (P = .089) for A. In addition, in cohort a, the relative risk of dying in the group that received A as compared with B was 0.2 (univariate Cox model). There were also survival trends in favor of A versus B (P = .18 and P = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42, respectively. In cohort b, the survival benefit could not be ascribed to vaccine quality alone, because of prognostic imbalance in favor of A. CONCLUSION: In cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV-NDV vaccine quality, since prognostic factors were not biased. This could imply clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality vaccine. Furthermore, the data provide clinically relevant information for standardization and quality control of autologous tumor-cell vaccines. A randomized study is urgently needed.

Breast Neoplasms

German family study on hereditary breast and/or ovarian cancer: germline mutation analysis of the BRCA1 gene.

Women harboring BRCA1 germline mutations carry an 85% lifetime risk of developing breast cancer and a 63% risk of ovarian cancer. In this first systematic study of familial breast and/or ovarian cancer in Germany we investigated 29 families for germline mutations in the BRCA1 gene. We identified mutations in three breast cancer families and in four breast-ovarian cancer families. The mutations include one missense mutation, one frameshift mutation, one splice mutation, and four nonsense mutations cosegregating with breast and/or ovarian susceptibility in five of ten (50%) families showing positive evidence of linkage to chromosome band 17q21 and in two of 19 (11%) families where linkage data was not available. Two apparently unrelated families carried the same nonsense mutation at codon 1835 and three families harbored a C to T transition at nucleotide 49 of the untranslated exon 4. Allelotyping of the markers D17S855, D17S1322, D17S1323, and D17S1327 located within or near BRCA1 revealed that all affected individuals in the two families harboring the mutation at codon 1835 shared at least one allele indicating a founder mutation. With respect to the overall mutation spectrum, no mutations were identified in exon 11 (0/7) in this set of German families. These findings differed significantly from those in British (17/32)(P = 0.012) and Southern Swedish (13/15) (P < 0.001) families. The lack of BRCA1 mutations in exon 11 which represents 61% of the entire coding sequence may provide additional insight into BRCA1 associated breast and ovarian tumor development.

BRCA1 Protein

[Cardiotocographic changes after umbilical cord puncture and umbilical cord transfusion].

In connection with umbilical cord punctures and transfusions the degree of pathology still tolerable after these procedures as well as the influence on subsequent obstetric management has to be discussed. In a prospective study we evaluated 98 cordocenteses with (n = 44) and without (n = 54) transfusion (25-37 week of gestation). 30-160 ml of blood were transfused. In all cases the umbilical vein was punctured at the point of insertion into the placenta (46x posterior and 52x anterior wall placenta). A CTG was performed prior and after the punction and was evaluated according to the Fischer score. After the procedure, the course of pregnancy was normal in all puncture patients and in 52 of 54 patients who also underwent a transfusion. Because of a pathological CTG due to a severely hydroptic fetus, a caesarean section had to be performed in one woman seven hours after umbilical cord transfusion. In another patient an emergency section was necessary immediately after the umbilical cord transfusion, due to persistent fetal bradycardia. In the puncture group mean Fischer score values decreased from 9.1 to 7.5, in the transfusion. In another patient an emergency section was necessary immediately after the umbilical cord transfusion, due to persistent fetal bradycardia. In the puncture group mean Fischer score values decreased from 9.1 to 7.5, in the transfusion group from 8.6 to 7.4. The results were more unfavorable when amplitude and occurrence of accelerations were considered, especially in the transfusion group. In one fifth of the puncture cases and one fourth of the transfusion patients the criterium of baseline crossings improved after the procedure. In summary, a pathological CTG is to be expected after umbilical cord punctures and transfusions, with however, only the necessity of surveillance. Only in cases of persistent fetal bradycardia an active obstetric management is indicated.

Blood Transfusion, Intrauterine

[Telecommunication--a medium for improving prenatal diagnosis and gynecologic ultrasound diagnosis? Initial experiences].

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.

Adult

[Paraneoplastic retinopathy in 2 patients with breast carcinoma].

Paraneoplastic retinopathies are rare paraneoplastic phenomena resulting in retinal degeneration. They occur in association with different tumor types, yet most frequently encountered in small cell carcinoma of the lung. Clinical symptoms may be present before the diagnosis of the underlying malignancy. They are characterized clinically by progressive visual loss with ring scotomas, photopsia and night-blindness. An autoimmune disorder is suggested. In the sera of patients antiretinal antibodies may be detected that are sometimes reactive with the 23 kD retinal antigen recoverin, a photoreceptorprotein. We report on two patients with breast cancer who developed paraneoplastic retinopathy during the course of disease. Immunologic tests showed antiretinal antibodies that were not reactive with the 23 kD retinal antigen recoverin.

Autoantibodies

[Doppler score for evaluating perinatal risk].

Doppler sonography now has a definite place in the surveillance of risk pregnancies. Uniform clinical management is sometimes difficult especially in borderline cases. The following study demonstrates the possibility of standardizing and systematizing Doppler results using a score. In a collective of 253 pregnant women we performed Doppler examinations in the fetal aorta, umbilical artery, middle cerebral artery, internal carotid artery. The results were divided into 4 groups and correlated to the fetal outcome. There was a highly significant worsening in prognosis regarding duration of pregnancy, birth weight and rate of cesarean sections with increasing Doppler score. In the event of pathological and highly pathological scores, the average duration of pregnancy was 23 and 48 days shorter than normal. As a result, there was a highly significant reduction in the average birth weight compared to fetuses with normal Doppler scores: by 1060.7 g in the case of a pathological score and by 1633.5 g in the case of a highly pathological score. There was a highly significant correlation concerning the rate of cesarean sections and the indication "fetal distress". The average interval between diagnosis and birth was 6.3 days in the case of pathological Doppler findings and 2.3 days in the case of highly pathological findings. The difference was highly significant. In the case of highly pathological scores all fetuses were delivered after at least 5 days, compared with after at least more than 10 days in those with only pathological Doppler findings. This reflects the fact that there is none room for discretion in case of a highly pathological flow. In summary the Doppler score allows better estimation of fetal risk and can improve fetal prognosis by special monitoring and earlier obstetric intervention.

Birth Weight

[Increased AFP in maternal serum as an indication for invasive diagnosis].

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.

Abdominal Muscles

Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status.

BACKGROUND: Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10%-20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow. PURPOSE: In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery. METHODS: Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant disease-free survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided. RESULTS: Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph node-negative patients. TCD was associated with larger tumors (P < .001), lymph node involvement (P = .001), and higher tumor grade (i.e., more undifferentiated) (P = .002). After a median follow-up of 36 months, patients with tumor cells in their bone marrow experienced reduced distant disease-free survival and overall survival (both P values < .001). TCD was an independent prognostic indicator for both distant disease-free survival and overall survival that was superior to axillary lymph node status, tumor stage, and tumor grade. Among patients with tumors less than 2 cm in diameter, TCD was the most powerful predictor of outcome. CONCLUSIONS AND IMPLICATIONS: TCD in the bone marrow of patients with breast cancer is a valuable prognostic tool associated with negligible morbidity. Prospective randomized studies should be performed to determine whether TCD might replace axillary lymph node dissection in a defined subgroup of patients with small tumors.

Adult

Allelic imbalance on chromosome 13q: evidence for the involvement of BRCA2 and RB1 in sporadic breast cancer.

Recently, the breast cancer susceptibility gene BRCA2 has been identified in chromosome 13q, a region that also contains the retinoblastoma gene RB1. To elucidate a possible role of BRCA2 and RB1 in sporadic breast tumorigenesis, allelic imbalance (AI) at 13q loci was examined in 78 primary sporadic breast tumors. AI was found in 52-63% of tumors. Nine tumors showed AI only in the BRCA2 region but not at RB1. Six tumors showed AI at RB1 but not in the BRCA2 region. AI in the BRCA2 region correlated significantly with aneuploidy (P = 0.032) and AI at RB1 with small tumor size (P = 0.025). Our data suggest that BRCA2 and RB1 may be both distinct target loci for AI on chromosome 13 in sporadic breast cancer.

Alleles

[Metastasis to the sternum or parasternal recurrence of breast carcinoma? Value of sonography].

Because of the high tendency of breast cancer to develop metastatic deposits in the skeleton, space-occupying processes in the sternal region are mostly attributed to osseous metastases and not to parasternal lymph node involvement, even in case of solitary lesions, primary tumor localizations in the inner quadrants, positive axillary nodes and negative X-ray or bone scan findings. The sonographic examinations of 115 patients with breast cancer and clinical and/or scintigraphic suspicion of sternal metastasis, however, revealed the typical bone metastases of the sternum with a small soft tissue tumors in only 27.8 %, whereas 59.1 % of the cases showed parasternal recurrences; 5.2 % had both. Non-tumorous changes were seen in 6.1 %, equivocal results in 1.7 %. Solitary osseous metastasis of the sternum was rare; multiple skeletal lesions were found in the majority of this group in contrast to the patients in the parasternal relapse group, which moreover showed strong overrepresentation of the primary tumor localization in the inner quadrants. X-rays of the chest or the sternum were often false-negative and not reliable, the bone scans positive only in cases of secondary sternal invasion or skeletal metastases. Concerning reliability and cost, sonography was the imaging method of first choice for diagnosis, therapy planning and follow-up for space-occupying processes in the sternal region, with CT or MRI as adjuncts in cases of extended tumors invading the mediastinum.

Adult