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Biomedical subjects

T Fehm

Publications and source records attributed to T Fehm.

12 recordsLinked to original sources

Detection of disseminated tumor cells in patients with gynecological cancers.

OBJECTIVES: The presence of disseminated tumor cells (DTC) in breast cancer patients is associated with poor prognosis. However, there are limited data about the prevalence and prognostic impact of DTC in patients with gynecological tumors. The aim of this study was to evaluate the presence of DTC in the bone marrow (BM) of patients with gynecological cancers and to correlate their presence with established prognostic factors. METHODS: BM aspirates of 201 patients with primary ovarian (n=69), cervical (n=54) and endometrial cancer (n=78), undergoing surgery at the Department of Gynecology and Obstetrics, University Hospital, Tuebingen, Germany between 1/2002 and 01/2006, were included into the study. Cytokeratin (CK)-positive cells were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. RESULTS: The bone marrow positivity rate was 36% in ovarian, 26% in cervical and 17% in endometrial cancer, respectively. Presence of DTC was significantly correlated with FIGO (International Federation of Gynecology and Obstetrics) tumor stage (p<0.05). The recurrence rate was 14% in patients with CK-positive cells compared to 8% in CK-negative patients (p=0.2). There was no correlation between DTC and other established prognostic factors including nodal status or grading except for cervical cancer. Patients with positive lymph node status were more likely to be bone marrow positive compared to those with negative lymph node status (p<0.05). CONCLUSIONS: Disseminated tumor cells seem to be a general phenomenon in epithelial tumors even though their clinical impact remains to be evaluated. The hypothesis that bone marrow is the homing site of disseminated tumor cells is further supported by these data since gynecological tumors only rarely metastasize to the skeletal system.

Bone Marrow↗

Cystic colon duplication as differential diagnosis to ovarian cyst.

OBJECTIVE: We report the case of a female fetus with a single spherical anechoic cyst on the right side of the lower abdomen first diagnosed at 22 weeks of pregnancy. METHODS: Serial ultrasound monitoring and needle aspiration of the cyst were performed. RESULTS: The cyst grew during pregnancy up to 8 cm diameter. Needle aspiration was performed at 33 and 36 weeks. At 38 weeks labor was induced and a girl was delivered spontaneously. Postnatally the child showed abdominal distention, vomiting, and an obstruction of venous return of the right leg. To improve venous circulation, another needle aspiration of the cyst was performed. Laparoscopy revealed cystic colon duplication. CONCLUSIONS: Prenatal differentiation of a single round anechoic cyst in the pelvis of a female fetus can be difficult. As a rare abnormality cystic colon duplication has to be considered.

Adult↗

Prenatal ultrasound diagnosis, follow-up, and outcome of congenital varicella syndrome.

OBJECTIVES: To report on a case of fetal varicella infection following the diagnosis of maternal infection at 16 weeks of gestation. METHODS: Diagnosis was based on serology testing and prenatal ultrasound, confirmed by DNA detection in amniotic fluid (Lightcycler-PCR). Serial ultrasound examinations were performed. RESULTS: Sonographic anomalies included borderline ventriculomegaly, intracerebral, intrahepatic and myocardial calcifications, limb deformities, articular effusions, and intrauterine growth retardation (confirmed postpartally). The newborn showed a severe encephalopathy and could not be stabilized sufficiently. The child died 23 days after birth. CONCLUSION: The outcome of an affected fetus may be very serious and prenatal ultrasound is a helpful tool to recognize the severity of the infection.

Brain Diseases↗

Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells.

Novel assay methods developed for the isolation and characterization of circulating tumor cells (CTC) of epithelial origin offer the potential of markers for the non-invasive gathering of clinical information relevant to the diagnosis, evolution and treatment of carcinoma. Of the numerous techniques currently used to analyze CTC, slide-based assays are perhaps the most common. While traditional combined immunocytochemical/brightfield microscopy systems continue to be the most frequently employed, fluorescence-based analysis is gaining in importance. This is partly because fluorescence microscopy analysis of slide-mounted CTC can provide simultaneously cytogenetic as well as morphologic and multiple phenotypic information. In particular, fluorescence microscopy analysis of slide-mounted CTC can accurately determine genetic changes at the chromosomal level in patients with recurrent disease. More importantly, by identifying genetic aberrations in CTC, it becomes possible to choose those patients most likely to benefit from a given treatment. The potential of this technique has already been demonstrated by employing fluorescence in situ hybridization (FISH) methods to measure expression of the HER2/neu gene in tissue from patients with breast carcinoma for the specific purpose of identifying those patients most likely to respond to Trastuzumab targeted therapy. Here, we review the major methodologies used in the preparation and analysis of the slide-based assays.

Carcinoma↗

Hemodynamic changes with phenotype reversal during pregnancy in twin-twin transfusion syndrome.

OBJECTIVES: We report an atypical case of twin-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twins with arterio-arterial anastomoses in which the former donor became the recipient during pregnancy. METHODS: Serial sonographic monitoring was performed. RESULTS: There was a phenotype reversal in TTTS concerning growth and amniotic fluid ending at 27 weeks, with the dominance of the former smaller donor. Doppler sonography changed from absent enddiastolic flow of the donor to normal values in both twins. The new recipient showed transient ascites, the now smaller actual donor (former recipient) developed progressive cardiomegaly, hypertrophy of the myocardium and mitral and tricuspid insufficiency at 29 weeks. Doppler sonography in the new donor deteriorated to highly pathologic flow in the venous system, leading to cesarean section. The donor fetus died 12 h after delivery because of myocardial decompensation. The recipient did very well and was discharged 8 weeks later from the neonatology unit. CONCLUSION: This atypical course shows the importance of serial sonographic monitoring in pregnancies with TTTS.

Adult↗

Fetal gender and sonographic assessment of crown-rump length: implications for multifetal pregnancy reduction.

OBJECTIVES: Fetal size is a common criterion for the selection of an individual fetus to be reduced during multifetal pregnancy reduction. We investigated whether a difference in crown-rump length (CRL) exists between male and female fetuses at 9-13 weeks' gestation. METHODS: A total of 883 singleton pregnancies was evaluated at the time of chorionic villus sampling. The mean gestational age at the time of intervention was 10.9 weeks. Pregnancies were dated by certain last menstrual period (LMP). Pregnancies with uncertain dating by LMP or with a sonographic difference of gestational age > 1 week compared with LMP were excluded, as were all cases with chromosomal abnormalities. CRL differences between male and female fetuses were compared using Student's t-test. RESULTS: A total of 417 female and 466 male fetuses fulfilled our study criteria. Their gestational ages ranged between 9.3 and 13.9 weeks. We found no significant difference in size between the male and female fetuses. CONCLUSION: Using the CRL to guide multifetal pregnancy reduction should not result in a clinically significant selection of either gender.

Crown-Rump Length↗

Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up.

PURPOSE: To evaluate the detection of epithelial cells in bone marrow of breast cancer patients as an indicator of metastatic disease. PATIENTS AND METHODS: Between 1989 and 1994, bone marrow biopsies were performed on 393 breast cancer patients during primary surgery. Specimens were stained immunocytochemically for epithelial cells expressing cytokeratins or the epithelial membrane antigen. The long-term outcomes of these patients were analyzed in this study. RESULTS: In 166 of 393 patients, epithelial cells were found in bone marrow (BM) aspirates. These patients were designated BM+. The rate of tumor recurrence or cancer-related death was significantly higher in BM+ patients than in BM- patients. Multivariate analysis using the Cox regression model revealed BM status as a prognostic parameter independent of tumor size and axillary lymph node status. However, tumor size and axillary lymph node status were clearly superior prognostic parameters. CONCLUSION: Disseminated epithelial cells in BM are associated with poor clinical outcome in breast cancer patients. However, the presence of these cells is not a sufficient parameter to predict growing metastases in the majority of patients, suggesting that epithelial cells in the BM of breast cancer patients at the time of surgery have limited metastatic potential. The role of these cells needs to be further evaluated.

Adult↗

CA 125 elevations in patients with malignant lymphomas.

Circulating CA 125 serum levels were measured in 60 patients with several hematological malignancies. Using 35 U/ml as cutoff level, elevated CA 125 concentrations were found in 3 of 18 patients with acute leukemia, 1 of 5 patients with chronic myelocytic leukemia, 2 of 9 patients with Hodgkin's lymphoma and in 14 of 28 patients with non-Hodgkin's lymphoma. None of the healthy control group had CA 125 serum levels above 35 U/ml. In patients with malignant lymphoma, elevated CA 125 serum concentrations were associated with abdominal involvement (p < 0.01). 15 of 19 patients with abdominal tumor masses had CA 125 concentrations above 35 U/ml, but only 1 of 18 patients with supradiaphragmatic involvement. Serial determinations of CA 125 were performed in 3 patients with malignant lymphoma during chemotherapy. Disease regression was associated with decreasing CA 125 serum levels. Thus, CA 125 may be a useful indicator of abdominal involvement in patients with malignant lymphoma. Moreover, serial CA 125 measurement may be of value in monitoring response to chemotherapy in these patients.

Acute Disease↗

Influence of circulating c-erbB-2 serum protein on response to adjuvant chemotherapy in node-positive breast cancer patients.

This retrospective case control study investigated the therametric value of the circulating c-erbB-2 gene product (Her-2, NEU) as (1) an eligibility criterion for high doses of chemotherapy and (2) response to standard adjuvant chemotherapy in node-positive breast cancer patients. Preoperative c-erbB-2 levels were measured in 211 locally advanced (> 3 nodes positive), pre- and perimenopausal breast cancer patients to determine if circulating levels of the gene product can assist in the determination of appropriate therapeutic options. 152 of 211 breast cancer patients received post-operatively a combination chemotherapy including the anthracycline analog mitoxantrone, while 59 patients were treated with conventional CMF therapy. Using 120 fmol/ml as a cut-off level, elevated c-erbB-2 values were found in 26 (12.3%) patients with locally advanced breast cancer. In univariate analysis significant survival differences were detected when c-erbB-2 'positive' patients were compared with c-erbB-2 'negative' patients. However, no significant survival differences were detected, when c-erbB-2 'positive' patients were compared according to regimen of adjuvant treatment. In multivariate analysis c-erbB-2 was an independent prognostic factor for predicting disease-free survival, but not for overall survival. High levels of c-erbB-2 were associated with low estrogen and progesterone receptor concentrations of the tumor cytosol. There was no correlation between elevated c-erbB-2 values and age, tumor size or degree of nodal involvement. c-erbB-2 was a better predictor of risk of recurrence than extent of nodal involvement or hormone receptor status.

Antineoplastic Combined Chemotherapy Protocols↗

The prognostic significance of c-erbB-2 serum protein in metastatic breast cancer.

The relationship between c-erbB-2 serum positivity and prognosis was evaluated in 80 patients with metastatic breast cancer. Using 120 fmol/ml as a cutoff level, elevated concentrations were found in 31 patients (38.8%) at the time of detection of metastases. Menopausal status, steroid receptor status, site of recurrence, initial tumor size, initial degree of nodal involvement as well as relapse-free interval were unrelated to c-erbB-2 serum positivity. In addition, no association could be found between adjuvant chemotherapy and positive c-erbB-2 concentrations. Patients with elevated c-erbB-2 levels showed a lower response rate (including complete remission, partial remission, no change) to first-line therapy than those with normal levels (29 vs. 59%, p < 0.01). The median survival time after relapse was 12 months (CI: 3-22 months) for the c-erbB-2-negative patients and only 6 months (CI: 3-8 months) for the c-erbB-2-positive group (p < 0.01). In the multivariate analysis, while c-erbB-2 levels at the time of primary surgery had no significant impact on survival in metastatic breast cancer, serum c-erbB-2 turned out to be the strongest factor for predicting survival after relapse.

Adult↗

Influence of tumor biological factors on tumor cell dissemination in primary breast cancer.

BACKGROUND: The presence of disseminated tumor cells in the bone marrow (BM) of breast cancer patients is associated with poor prognosis and may therefore be related to aggressive breast cancer as indicated by tumor biological and clinicopathological factors. The aim of this study was to identify those features of the primary tumor related to the presence of disseminated tumor cells in the BM. PATIENTS AND METHODS: Clinical data from 508 primary breast cancer patients were analyzed. Tumor biological features of the primary tumor including HER2, p53, Ki-67, bcl-2 and hormone receptor status, as well as clinicopathological factors including histology, menopausal status, lymph node status, tumor size and grade, were studied for their association with BM involvement by univariate and multivariate analysis. RESULTS: Two-hundred and two out of 508 (40%) primary breast cancer patients had disseminated tumor cells in the BM. p53 expression, hormone receptor status, HER2 and Ki-67 were significantly related to BM involvement. The multivariate analysis revealed that p53 expression (OR: 1.9, 95% CI: 1.2 - 3.0) followed by progesterone receptor status (OR: 1.5, 95% CI: 1.0 - 2.2) were the only independent determinants for BM involvement. CONCLUSION: The presence of disseminated tumor cells in the BM was not influenced by tumor load as reflected by tumor size and lymph node involvement, whereas tumor biological factors were independently correlated to BM involvement. The results substantiate the important role of tumor biological factors of the primary tumor for tumor cell dissemination.

Bone Marrow↗

Changes of serum HER2 status during clinical course of metastatic breast cancer patients.

BACKGROUND: Serum HER2 testing allows the determination of the real-time HER2 status of breast cancer patients. The aim of this investigation was to study (i) whether changes of serum HER2 status occur during the clinical course of breast cancer and (ii) to evaluate the prognostic significance of serum HER2 status, at the time of first diagnosis of primary breast cancer and at the onset of metastatic disease, for survival after relapse (SAR). MATERIALS AND METHODS: HER2 serum levels were retrospectively measured in 152 breast cancer patients at the time of first diagnosis of breast cancer and at the onset of metastatic disease by enzyme immunoassay. RESULTS: Twenty-seven out of 152 (18%) patients had elevated HER2 serum levels at the time of first diagnosis of breast cancer. In contrast, 56 out of 152 (37%) patients showed elevated serum HER2 levels when metastases were diagnosed. A change of serum HER2 status during clinical course was observed in 43 out of 152 (28%) patients. Serum HER2 status at the time of first diagnosis of breast cancer had no impact on survival after relapse (SAR) (p = 0.4). However, the median SAR for serum HER2-positive patients at the onset of metastatic disease was significantly shorter (8 months, 95% CI: 3-12) compared to patients serum HER2-negative at this time (18 months, 95% CI: 14-22) (p < 0.01). CONCLUSION: Serum HER2 status can change during the course of disease. Therefore, the serum HER2 status should be re-evaluated at the time of diagnosis of metastatic disease to optimize treatment decisions.

Breast Neoplasms↗