Beneficial effects of a 6-month dietary restriction are time-dependently abolished within 2 weeks or 6 months of refeeding-genome-wide transcriptome analysis in mouse liver.

Dietary restriction (DR) has been shown to exert a number of beneficial effects including the prolongation of life span. One of the mechanisms by which DR leads to these advantages seems to be the induction of endogenous antioxidant defense and stress response mechanisms. However, little is known about the persistence of DR benefits after return to an ad libitum diet. In this study, male C57BL/6 mice were fed 75% of a normal diet for 6 months (DR) followed by 6 months of ad libitum refeeding (RF) and compared to a continuously ad libitum fed control group. To study the impact of DR and RF on the liver transcriptome, a global gene expression profile was generated using microarray technology. In comparison, the DR group showed lower body weight, lower triglyceride and cholesterol levels, reduced lipid peroxidation, and a changed hepatic fatty acid pattern. mRNA transcription and activity of antioxidant and phase II enzymes, as well as metallothionein 1 gene expression, were increased and autophagy was induced. Shifting from long-term DR to RF abolished 96% of the DR-mediated changes in differential gene expression within 2 weeks, and after 6 months of refeeding all of the previously differentially expressed genes were similar in both groups. These results indicate that DR has to be maintained continuously to keep its beneficial effects.

Positron emission tomography for the diagnosis of breast cancer.

This article reviews the literature on breast imaging with [18F]fluorodeoxyglucose positron emission tomography (FDG PET). In clinical applications, there is currently no defined role for detecting primary breast cancer. The limited sensitivity of FDG PET does not allow the exclusion of malignancy, in particular small breast carcinomas, micrometastases and small, tumour infiltrated lymph nodes. However, in advanced stages, PET accurately determines the extent of disease, including the loco-regional lymph node status. Furthermore, whole-body PET imaging promises a high diagnostic accuracy for detecting recurrent or metastatic breast carcinoma. Future clinical applications may include monitoring therapeutic effects.

Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis.

UNLABELLED: Breast cancer is characterized by elevated glucose consumption resulting in increased uptake of 18F-FDG. However, tracer uptake varies considerably among tumors imaged with PET. This study compared histologic and immunohistochemical tissue analysis of breast carcinomas with preoperative FDG uptake assessed by PET to identify tumor characteristics that define the degree of tracer accumulation. METHODS: FDG uptake in breast tumors was quantified by calculating standardized uptake values (SUVs) corrected for partial-volume effect and normalized to blood glucose level at the time of tracer injection. The histologic sections of 50 invasive and 6 noninvasive breast carcinomas were analyzed for histologic type, microscopic tumor growth pattern, percentage of tumor cells, presence of inflammatory cells, density of blood vessels, histopathologic grading, tumor cell proliferation (mitotic rate and antibody binding of MIB-1), expression of estrogen and progesterone receptors, and expression of the glucose transporter protein Glut-1. RESULTS: A positive correlation was found between FDG uptake and histologic tumor type (ductal vs. lobular; P = 0.003), microscopic tumor growth pattern (nodular vs. diffuse; P = 0.007), and tumor cell proliferation (MIB-1; P = 0.009). Tumors with diffuse growth patterns had significantly lower SUVs compared with clearly defined tumors. A weak relationship was found between FDG uptake and the percentage of tumor cells (P = 0.06). Lower densities of blood vessels corresponded to higher FDG uptakes (P = 0.08). However, even significant correlations showed poor correlation coefficients. No relationship was found between FDG uptake and the following: tumor size; axillary lymph node status; percentage of necrotic, fibrotic, and cystic compounds; presence of inflammatory cells; steroid receptor status; and expression of Glut-1. CONCLUSION: Histologic and immunohistochemical tissue analysis was unable to sufficiently explain the variation of FDG uptake in breast cancer. The degree of metabolic changes after malignant transformation is most likely explained by a complex interaction between cellular energy demand and tumoral microenvironment. Therefore, FDG PET imaging may not be used to estimate tumor biologic behavior of breast cancer such as differentiation, histopathologic grading, cell proliferation, or axillary lymph node status.

Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations.

PURPOSE: To evaluate the diagnostic value of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) for the diagnosis of primary breast cancer. PATIENTS AND METHODS: Preoperatively, 144 patients with masses suggestive of breast cancer underwent PET imaging of the breast. To identify breast cancer by increased metabolic activity, parametric FDG-PET images were analyzed for increased tracer uptake applying conventional image reading (CIR) and sensitive image reading (SIR). One hundred eighty-five breast tumors were evaluated by histology, revealing 132 breast carcinomas and 53 benign masses. RESULTS: Breast carcinomas were identified with an overall sensitivity of 64.4% (CIR) and 80.3% (SIR). The increase in sensitivity (SIR) resulted in a noticeable decrease in specificity, from 94.3% (CIR) to 75.5% (SIR). At stage pT1, only 30 (68.2%) of 44 breast carcinomas were detected, compared with 57 (91.9%) of 62 at stage pT2. A higher percentage of invasive lobular carcinomas were false-negative (65.2%) compared with invasive ductal carcinomas (23.7%). Nevertheless, positive PET scans provided a high positive-predictive value (96.6%) for breast cancer. CONCLUSION: Partial volume effects and varying metabolic activity (dependent on tumor type) seem to represent the most significant limitations for the routine diagnostic application of PET. The number of invasive procedures is therefore unlikely to be significantly reduced by PET imaging in patients presenting with abnormal mammography. However, the high positive-predictive value, resulting from the increased metabolic activity of malignant tissue, may be used with carefully selected subsets of patients as well as to determine the extent of disease or to assess therapy response.

Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer.

PURPOSE: To address the role of positron emission tomography (PET) using [(18)F]fluorodeoxyglucose (FDG) to monitor primary (neoadjuvant) chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS: Quantification of regional FDG uptake of the breast acquired after the first and second courses of chemotherapy was compared with the baseline scan in 22 patients with a total of 24 breast carcinomas. To evaluate the predictive value of PET imaging, histopathologic response after completion of chemotherapy classified as gross residual disease (GRD) or minimal residual disease (MRD) served as the gold standard. RESULTS: Significant differences in tracer uptake between nonresponding tumors (GRD) and responding lesions (MRD) were observed (P <.05) as early as after the first course of chemotherapy. Tracer uptake showed little change in tumors with GRD found later in pathologic analysis but decreased sharply to the background level in most tumors with MRD. After the first course, all responders were correctly identified (sensitivity 100%, specificity 85%) by a standardized uptake value decrease below 55% of the baseline scan. At this threshold, histopathologic response could be predicted with an accuracy of 88% and 91% after the first and second courses of therapy, respectively. CONCLUSION: This study demonstrates that in patients with advanced breast cancer undergoing primary chemotherapy, FDG-PET differentiates responders from nonresponders early in the course of therapy. This may help improve patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose-intensive preoperative chemotherapy in responding patients.

Detection of Intramural Choriocarcinoma of the Uterus with 18F-FDG-PET. A Case Report.

We are reporting the case of a 37-year-old woman with rising beta-human chorionic gonadotropin (HCG) levels over 4 years. Curettage was performed 5 times and diagnostic laparoscopy twice, but no trophoblastic tissue was found. Vaginal ultrasound and power Doppler sonography showed a solid tumor of the anterior uterus wall with high vascularization. 18F-2-deoxy-D-glucose-positron emission tomography (FDG-PET) revealed a single focus of FDG uptake in projection of the uterus. Sonographically, the tumor of the uterus appeared like a leiomyoma. Thus focal FDG uptake was the sole indicator for a malignant trophoblastic tumor. Histological examination of the tumor revealed a choriocarcinoma.

Effect of attenuation correction on lesion detectability in FDG PET of breast cancer.

UNLABELLED: The aim of this study was to compare the visual analysis of attenuation-corrected and noncorrected 18F-fluoro-2-deoxy-D-glucose (FDG) PET images in patients with primary or metastatic breast cancer using standardized film documentation and to evaluate the influence of attenuation correction on lesion detectability. METHODS: Standard FDG PET of the breasts and of the axillary regions was performed on 28 women with breast cancer. Transmission scans were acquired for attenuation correction after administration of FDG. Transverse and coronal slices and maximum intensity projections both with and without attenuation correction were documented in a standardized manner on film. Noncorrected images were displayed with an upper threshold of five times the mean activity in normal lung tissue. Attenuation-corrected images were documented with an upper threshold of a standardized uptake value of five. Two independent nuclear medicine physicians, who were unaware of the results of clinical investigation, other imaging modalities and histopathologic findings, interpreted the images visually, noncorrected images first. RESULTS: One hundred eighty-four of 189 lesions in 28 of 28 patients were found on attenuation-corrected and noncorrected images. Seventeen lesions were found in the breasts of 12 patients. In 18 patients, 31 axillary lesions were found. Moreover, 141 lesions representing distant metastases were detected in 18 patients. Attenuation-corrected images showed the same lesions in all patients but 2, in whom 5 of 189 small pulmonary lesions (2.6%) were not detected. Iterative reconstruction did not improve detectability of these lesions on attenuation-corrected images. These lesions were confirmed by CT, which revealed diameters of <1 cm. CONCLUSION: Attenuation correction by transmission measurement after injection may impair lesion detectability in PET for staging of breast cancer patients. When using the image modalities described, noncorrected PET images should be considered in image analysis.

Amphetamine administration improves neurochemical outcome of lateral fluid percussion brain injury in the rat.

This study examined the effects of the administration of D-amphetamine on the regional accumulation of lactate and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. Rats were subjected to either FP brain injury of moderate severity (1.9 to 2.0 atm) or sham operation. At 5 min after injury, rats were treated with either d-amphetamine (4 mg/kg, i.p.) or saline. At 30 min and 60 min after brain injury, brains were frozen in situ, and cortices and hippocampi were excised at 0 degrees C. In the saline-treated brain injured rats, levels of lactate were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. These increases were attenuated by the administration of D-amphetamine at 5 min after lateral FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of all individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex of the saline-treated injured rats. These increases in the ipsilateral cortex and hippocampus were also attenuated by the administration of d-amphetamine. Neither levels of lactate nor levels of FFAs were increased in the contralateral cortex in the saline-treated injured rats at 30 min or 60 min after FP brain injury. The levels of lactate and FFAs in the contralateral cortex were also unaffected by the administration of D-amphetamine. These results suggest that the attenuation of increases in the levels of lactate and FFAs in the ipsilateral cortex and hippocampus may be involved in the amphetamine-induced improvement in behavioral outcome after lateral FP brain injury.

Intradimensional transfer of duration matching-to-sample in pigeons with signals differing in color and location.

Duration matching-to-sample (MTS) was used to study the influence of signal attributes on temporal transfer in pigeons. Each of two groups was trained on two problems that involved 2 and 10 s duration samples that varied with respect to color and-or spatial location. For Group Color, signals were either a red or white light projected from the front wall. For Group Location, signals were a white light from either the front wall or the ceiling. Within each group, each combination of signal type (color or location) and duration was associated with a different choice stimulus, and one set of color choices always followed one signal type and a different set of color choices always followed the other signal type. Transfer tests involved a set of choices that had not previously been associated with the type of signal presented on that trial. Accuracy on transfer trials was very high in Group Color but at a chance level in Group Location, which indicates that temporal transfer occurs when signals emanate from the same location but not when signals emanate from different locations. These results are discussed in terms of other evidence of transfer of duration-MTS.

Impact of d-amphetamine on temporal estimation in pigeons tested with a production procedure.

The influence of d-amphetamine on timing in pigeons was examined with a production procedure. Birds were trained with a fixed time schedule in which food reinforcement was contingent on the first response made after a duration signal had appeared for 30 s. Probe tests involved trials in which the duration signal was extended to 90 s and reinforcement was omitted. In Experiment 1, 2.0 mg/kg d-amphetamine shifted peak responding to a duration shorter than that found with saline. In Experiment 2, the dose-response function for this drug effect was examined. A 0.3-mg/kg dose of d-amphetamine had no impact on performance, but a 1.0-mg/kg dose shifted the peak duration significantly relative to saline; a 2.0-mg/kg dose shifted the function even more. These results complement previous findings with rats tested with the peak procedure and pigeons tested with a discrimination procedure.

Breast imaging with fluorine-18-FDG PET: quantitative image analysis.

UNLABELLED: This study evaluated various quantitative criteria for analysis of breast imaging with PET using the radiolabeled glucose analog 18F-fluorodeoxyglucose (FDG). METHODS: In a prospective study, 73 patients with abnormal mammography or palpable breast masses scheduled for biopsy were investigated with PET. A total of 97 breast tumors were evaluated by histology, including 46 benign and 51 malignant tumors. Using a whole-body PET scanner, attenuation-corrected images were acquired between 40 and 60 min after tracer injection. For Patlak analysis, dynamic data acquisition was obtained in 24 patients. To differentiate between benign and malignant breast tumors, receiver operating characteristic curves were calculated using incrementally increasing threshold values for tumor/ nontumor ratios based on average and maximum activity values per region of interest, standardized uptake values (corrected for partial volume effect, normalized to blood glucose, partial volume effect and blood glucose, using the lean body mass as well as the body surface area) and calculating the FDG influx rate (K) assessed by Patlak analysis. RESULTS: Quantification of FDG uptake in breast tumors provided objective criteria for differentiation between benign and malignant tissue with similar diagnostic accuracy as compared with visual analysis. Applying correction for partial volume effect and normalization by blood glucose yielded the highest diagnostic accuracy. CONCLUSIONS: These quantitative methods provided accurate evaluation of PET data for differentiating benign from malignant breast tumors. Quantitative assessment is recommended to complement visual image interpretation with the potential benefit of reduced interobserver variability.

Time course of changes in lactate and free fatty acids after experimental brain injury and relationship to morphologic damage.

Regional levels of lactate and free fatty acids (FFA) were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min after injury, tissue concentrations of lactate were elevated in the cortices and hippocampi of both ipsilateral and contralateral hemispheres. Whereas lactate levels had returned to normal by about 20 min after injury in the penumbra and contralateral cortices, their elevation persisted in the ipsilateral injured cortex and hippocampus for 24 h after injury. Increases in the levels of FFA (particularly stearic and arachidonic acids) were observed in the cortices and hippocampi of both ipsilateral and contralateral hemispheres at 5 min after injury; these levels returned to normal in only the penumbra and contralateral cortices by 20 min after injury. Increased amounts of palmitic and oleic acids were also found only in the injured left cortex and ipsilateral hippocampus at 20 min or later after injury. In general, these elevations persisted for as long as 6 to 24 h in the injured cortex and for 2.5 to 24 h after injury in the ipsilateral hippocampus. Histologic studies revealed a similar extent of damage in the cortex between 5 min and 24 h after injury, whereas damage in the CA3 region of the ipsilateral hippocampus increased during that period. These findings suggest a role for lactic acid and FFA, two secondary injury factors, in neuronal cell loss after brain injury.

Lack of delayed effects of amphetamine, methoxamine, and prazosin (adrenergic drugs) on behavioral outcome after lateral fluid percussion brain injury in the rat.

This study examined the delayed effects of the administration of d-amphetamine, methoxamine (an alpha1-adrenergic receptor agonist), and prazosin (an alpha1-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid-percussion (FP) brain injury. Rats trained to perform a beam-walking task were subjected to brain injury of moderate severity (2.1 to 2.2 atm). Twenty-four hours after injury, rats were treated with amphetamine, methoxamine, or prazosin at two or three different dose levels. Amphetamine-treated animals displayed no significant improvement in beam-walking ability either during or after drug intoxication (from days 3 to 5 after brain injury). Similarly, neither methoxamine nor prazosin significantly affected beam-walking ability during or after drug intoxication. Neither amphetamine treatment at three different doses nor treatment with methoxamine or prazosin at two different doses affected the spatial learning disabilities of brain-injured animals. These results suggest that (1) unlike amphetamine administration after sensorimotor cortex (SMC) ablation or contusion brain injury models, amphetamine administration at 24 h after concussive FP brain injury does not improve beam-walking performance; (2) unlike amphetamine administration 10 min after concussive FP brain injury amphetamine administration 24 h after injury does not improve cognitive function; and (3) unlike prazosin administration after SMC ablation brain injury, prazosin administration 24 h after concussive FP brain injury does not effect beam-walking performance.

[Metabolic characterization of ovarian tumors with positron-emission tomography and F-18 fluorodeoxyglucose]. / Metabolische Charakterisierung von Ovarialtumoren mit der Positronen-Emissions-Tomographie und F-18-Fluordeoxyglukose.

PURPOSE: This study describes diagnostic accuracy of PET imaging in patients with ovarian tumours using histological diagnosis as gold standard. METHODS AND RESULTS: Pet studies were performed in 19 patients who were scheduled to undergo exploratory surgery for a suspicious ovarian mass and in 5 patients with suspected recurrence. The PET data were analyzed visually and quantitatively and compared to the histologic findings. 6 patients had ovarian cancer, while in 13 patients a benign tumour was found including inflammatory processes in 4 cases. All malignant tumours showed an enhanced FDG uptake with the exception of one false-negative borderline carcinoma. 4 cases with inflammatory processes as well as endometrial and follicular cysts revealed a high FDG uptake. A successful localisation of a recurrent tumour was possible in 4 out of 5 cases. Disseminated peritoneal carcinomatosis in two patients could not be detected by PET. CONCLUSIONS: Enhanced glucose metabolism of ovarian cancer enables PET diagnosis with a sensitivity of 83%. An intensive FDG uptake in inflammatory processes resulted in a specificity of only 54% in this study. The high sensitivity of PET for malignant tumours may be useful in the detection of recurrent ovarian cancer.

[Diagnosis of breast carcinoma and locoregional lymph nodes with positron emission tomography]. / Diagnostik des Mammakarzinoms und der lokoregionären Lymphknoten mit der Positronenemissionstomographie.

Based on the increased glucose metabolism of malignant tissue, positron emission tomography (PET), using the radiolabeled glucose analog 18F-fluorodeoxyglucose (FDG), allows identification of breast cancer. Based on the criteria implemented in image interpretation, sensitivity of PET imaging ranged from 68% to 94% with a specificity between 84% and 97%. However, sensitivity for small tumors (< 1 cm) was found to be low. PET demonstrates tumor involvement of regional lymph nodes with high accuracy, predominantly in patients with advanced breast cancer. The sensitivity for the detection of axillary lymph node metastases was 79%, increasing to 94% in patients with primary breast tumors larger than 2 cm in diameter. Corresponding specificities were 96 and 100%, respectively. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33% in these patients. By visualizing primary tumors and metastases in one imaging procedure, PET imaging may allow the effective staging of breast cancer patients. Response to treatment may be assessed at an earlier point than with imaging techniques currently used. Therefore, indications for PET studies in the future may be the evaluation of loco-regional lymph nodes, whole-body staging, diagnosis of local recurrence and therapy monitoring.

Regional generation of leukotriene C4 after experimental brain injury in anesthetized rats.

Regional concentrations of leukotriene C4 and extravasation of Evans blue were measured after lateral fluid-percussion brain injury in rats. Tissue levels of LTC4 were elevated in the injured cortex at 10 min, 30 min, and 1 h after injury; these levels returned to normal by 2 h after injury. Increases in the levels of LTC4 were also observed in the ipsilateral hippocampus after brain injury, and these elevations persisted for 2 h after injury. No significant increase in levels of LTC4 was observed in the contralateral cortex at any time after injury. A substantial extravasation of Evans blue was observed only in the ipsilateral cortex and hippocampus at 3 h and 6 h after brain injury. Although a temporal association between LTC4 and blood-brain barrier (BBB) breakdown is suggested by these data, no cause-and-effect relationship has been addressed in this study. However, it is possible that, as is true for cerebral ischemia, LTC4 may play a role as a mediator in the BBB breakdown associated with fluid-percussion brain injury in rats.

Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.

Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose.

PURPOSE: To evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors. PATIENTS AND METHODS: Fifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake. RESULTS: Primary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information. CONCLUSION: PET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.

-Intravenous or oral etoposide therapy of platinum refractory ovarian cancer with early recurrence. Results of a prospective randomized study-. / Die intravenöse oder orale Etoposid-Therapie des Platin-refraktären Ovarialkarzinom-Frührezidivs. Ergebnisse einer prospektiven randomisierlen Studie.

121 patients with advanced ovarian cancer resistant to or relapsing following platinum-based chemotherapy participated in this prospective randomised multicenter study. The second-line treatment was indicated according to the relapse-free interval. 36 assessable patients were resistant to platinum-based chemotherapy or relapsed within 12 months following primary surgery. This group of patients with early relapse was randomized to oral or parenteral etoposide. 82 patients relapsed within an interval longer then 12 months following primary surgery; these patients with delayed relapse underwent a secondary tumour-debulking surgery. The data of this group of patients with delayed relapse will be published as soon as the time of observation allows adequate results. In this paper the efficiency of etoposide in the patients with early relapse is analysed according to the application form of the drug (oral vs. parenteral). No statistically significant difference in response rate, toxicity, and median survival time was found between the oral (n = 18) and parenteral (n = 18) treatment. In both application groups the response rate was 22%, the median survival time 14 and 13 months respectively. Alopecia and leucopenia were the most frequent toxicities. As a result etoposide is efficient in unfavorable ovarian cancer patients with early relapse. Because of better compliance etoposide should be administered parenterally. In respect of response rate and median survival time, etoposide is comparable with paclitaxel.