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Background A multicenter phase II study was conducted to analyze the clinical activity of the steroidal aromatase inhibitor exemestane in the neoadjuvant treatment of post-menopausal women with strongly ER- and/or PgR- positive operable breast cancer. Patients and methods From September 2000 to December 2003, 80 women were recruited for treatment with exemestane 25 mg once daily for 4 months. The primary end-point was the clinical response rate according the WHO criteria; the secondary end-points included toxicity and the number of patients who qualified for breast conserving surgery at the end of treatment, comparability of evaluation methods for response, potential alterations of hormone receptor and Her2/neu status during treatment. Results On an intention to evaluate analysis, according to the prespecified criteria the overall clinical objective response rate was 34%, the pCR rate was 3% and the rate of breast conserving surgery was 76%. When sonographic and mammographic longitudinal measurements were included in patients with missing palpation data, response rates were 38% and 41%, respectively. The tumor response was independent of the Her2/neu status which remained unchanged during treatment. In contrast, while the ER expression remained unaltered, downregulation of the PgR was observed. The treatment was well tolerated with no grade 3 and 4 toxicities except gastrointestinal (one grade 3 case) and hot flushes (two grade 3 cases). Conclusion This study shows that exemestane is effective and safe as a preoperative therapy in post-menopausal patients with strongly hormone receptor-positive breast cancer.

The standard treatment for early breast cancer comprises wide local excision, sentinel lymph node biopsy or axillary lymph node dissection, adjuvant medical treatment and radiotherapy to the whole breast. Many studies suggest that local control plays a crucial role in overall survival. The local recurrence rate is estimated to be 1% per year and varies between 4 and 7% after 5 years and up to 10 to 20% in the long-term follow up. On the basis of low local recurrence rates the concept of whole breast irradiation comes up for discussion, and partial breast irradiation (PBI) is increasingly under consideration. Intraoperative radiotherapy (IORT) is referred to as the delivery of a single high dose of irradiation directly to the tumor bed (confined target) during surgery. PBI (limited field radiation therapy, accelerated partial breast irradiation APBI) is the irradiation exclusively confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery without whole breast irradiation. Various methods and techniques for IORT or PBI are under investigation. The advantage of a very short radiation time or the integration of the complete radiation treatment into the surgical procedure convinces at a first glance. The promising short-term results of those studies must not fail to mention that local recurrence rates could probably increase and furthermore give rise to distant metastases and a reduction in overall survival. The combination of IORT in boost modality and whole breast irradiation has the ability to reduce local recurrence rates. The EBCTCG overview approves that differences in local treatment that substantially affect local recurrence rates would avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Die Exzision von Sentinel-Lymphknoten (LK) bekommt eine zunehmende Bedeutung bei der Diagnostik von Mundhohlen- und Oropharynxkarzinomen im Falle eines N0-Halses. Die Sentinel-Node-Biopsie (SNB) wurde in ihrer Wertigkeit als einzige chirurgische Staging-Masnahme untersucht. Im Rahmen eines multimodalen Behandlungskonzeptes wurde die SNB ohne elektive Neck-Dissection (ND) bei 70 Patienten im Rahmen der Operation des Primarius durchgefuhrt. Die Kontrolle der Genauigkeit erfolgte uber die Manifestation von Hals-LK-Metastasen bei 45 Patienten, die keine postoperative Bestrahlung erhalten hatten. Es konnten in 94% der Falle Sentinel-LK exzidiert werden; 9 Patienten (13%) hatten positive LK und erhielten eine therapeutische ND. Es kam zu 2 Hals-LK-Metastasen im Zusammenhang mit Zweitkarzinomen, alle anderen Patienten blieben regionar unauffallig (mediane Beobachtungszeit: 26 Monate). Die SNB konnte als Staging-Masnahme beim N0-Hals und T1- bis T3-Tumoren zu einer erheblichen Reduktion der Anzahl elektiver NDs fuhren. Sie kann gut in ein multimodales Behandlungsschema integriert werden.

Intra-arterial iodine-131 labelled Lipiodol therapy for liver cancer has been investigated for safety and efficacy over a number of years, but data on radiation exposure of personnel have remained unavailable to date. The aim of this study was to assess the radiation exposure of the physician during intra-arterial 131I-Lipiodol therapy for liver malignancies and to develop appropriate radiation protection measures and equipment. During 20 intra-arterial administrations of 131I-Lipiodol (1110-1924 MBq), radiation dose equivalents (RDE) to the whole body, fingers and eyes of the physician were determined for (a) conventional manual administration through a shielded syringe, (b) administration with an automatic injector and (c) administration with a lead container developed in-house. Administration by syringe resulted in a finger RDE of 19.5 mSv, an eye RDE of 130-140 microSv, and a whole-body RDE of 108-119 microSv. The injector reduced the finger RDE to 5 mSv. With both technique (a) and technique (b), contamination of angiography materials was observed. The container allowed safe transport and administration of the radiopharmaceutical from 4 m distance and reduced the finger RDE to3 microSv and the eye RDE to1 microSv during injection. During femoral artery compression, radiation exposure to the fingers reached 170 microSv, but the whole-body dose could be reduced from a mean RDE of 114 microSv to 14 microSv. No more contamination occurred. In conclusion, radiation exposure was high when 131I-Lipiodol was administered by syringe or injector, but was significantly reduced with the lead container.

The diagnostic potential of technetium-99m hexamethylpropylene amine oxime (HMPAO) following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer’s disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPET slices were evaluated visually and semiquantitatively by a semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of the VD patients and in 70% (23/33) of the AD patients. The corresponding data obtained by quantitative evaluation were 41% (7/17) and 71% (15/21), respectively. The vascular reserve capacity, as determined with the acetazolamide test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The differences in the perfusion patterns between the VD and AD patients were statistically significant (P

In a patient with the occipitoparietal form of Creutzfeldt-Jakob disease (CJD) (Heidenhain type) positron emission tomography (PET) demonstrated decreased glucose utilization in the occipital lobes and adjacent cortical regions. Single photon emission computed tomography (SPECT) with 99mTc-bicisate showed a "coupled" decrease in blood flow in identical cortical areas in this patient. In contrast, magnetic resonance imaging (MRI) was normal. In the early stage of CJD, when still no major morphological abnormalities can be observed, functional imaging is useful for differential diagnosis, particularly to exclude other causes of dementia or pathological EEG patterns.

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with 131I) and a negative FDG PET, in four cases 131I-negative lymph node metastases were detectable with PET. Even in the patients with concordant "staging", differences between 131I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 131I-positive/FDG-negative, 131I-negative/FDG-positive and 131I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours 131I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.

Clinical outcome after myocardial infarction depends on the extent of irreversibly damaged myocardium. Implantation of bone marrow-/circulating blood-derived progenitor cells has been shown to improve contractile cardiac function after myocardial infarction in both experimental and initial clinical studies. In the present study, first observations of the effect of local intracoronary progenitor cell infusion on the regeneration of infarcted cardiac tissue after acute myocardial infarction was evaluated by means of 18F-fluorodeoxyglucose positron emission tomography (PET) and 201Tl single-photon emission computed tomography (SPECT). Twenty-six patients underwent intracoronary infusion of bone marrow-derived (BMCs) (15 patients) or circulating blood-derived endothelial progenitor cells (EPCs) (11 patients) 4+/-2 days after acute myocardial infarction. Based on a left ventricular segmentation model (17 segments), mean signal intensities as a parameter of viability and perfusion in the infarct zone and non-infarct areas were calculated quantitatively by PET and SPECT at baseline and at 4 months of follow-up. Transplantation of progenitor cells was associated with a significant increase in the mean signal intensity (MSI) in the infarct zone from 54.5% (25th and 75th percentiles: 47.7%, 60.0%) to 58.0% (52.7%, 66.7%) on PET (P=0.013) and from 58.0% (49.5%, 63.0%) to 61.5% (52.5%, 70.2%) on SPECT (P=0.005). Global left ventricular ejection fraction (LVEF) increased from 53.5% (42.6%, 60.0%) to 58.0% (53.0%, 65.8%) (P0.001). In the five patients without an increase in MSI on PET, LVEF changed from 60.0% (50.0%, 64.0%) to 72.0% (64.0%, 75.5%) at follow-up. PET and SPECT did not show any significant changes in MSI in the non-infarct areas [from 73% (68.5%, 76.2%) to 73% (69.7%, 78.0%) for PET and from 72.0% (66.5%, 77.6%) to 73.0% (67.5%, 78.2%) for SPECT]. There were no significant differences in myocardial viability and perfusion between BMC and EPC infusion. These preliminary results show that coronary stenting and transplantation of progenitor cells result in a significant increase in myocardial viability and perfusion. Therapeutic effects can be reliably measured by PET and SPECT.

Vascularisation of coralline hydroxyapatite used to replace the enucleated bulb is of critical importance for the uncomplicated implantation of a motility peg connecting the implant with the cosmetic prosthesis. Technetium-99m diphosphopropanedicarboxylic acid (DPD) single-photon emission tomography (SPET) was used to evaluate the rate of vascularisation as well as the time required for completion of vascularisation. Twenty-four patients were enrolled in the study, which was designed to evaluate vascularisation 10 days, 2 months and 4 months after implantation of a coralline implant. Nineteen patients completed the study and the visual impression of the completion of the vascularisation was scored from 0 (no vascularisation) to ++++ (complete vascularisation) for each patient. No tracer accumulation was detected in any patient at the 10-day examination. Increasing vascularisation was demonstrated with time, and full vascularisation of the coralline implant was seen in all but one case by 4 months after implantation. We conclude that vascularisation of ocular coralline hydroxyapatite implants occurs early and is completed by 4 months after implantation in most cases, but should be confirmed at this time by99mTc-DPD SPET.

The clinical application of technetium-99m bicisate (ethyl cysteinate dimer, ECD) for ictal and interictal studies of regional cerebral blood flow (rCBF) in a patient suffering from medically intractable simple and complex partial seizures is reported. The interictal study was performed 60 min p.i. and the ictal studies were performed at 60 min p.i. using an annular crystal single photon emission tomography (SPET) system dedicated for high-resolution brain SPET imaging. Visual evaluation of the studies was carried out, as well as semiquantitative measurement of regional tracer uptake. Magnetic resonance imaging (MRI) scans revealed atrophy of almost the complete left frontal lobe and the ventral parts of the left temporal lobe, including in part the temporomesial structures. The left parietal and occipital structures and the right hemisphere were normal. The interictal study showed a large perfusion defect involving the whole left frontal lobe as well as the left temporal lobe with remaining small areas of normal cortical tracer uptake. The ictal studies detected circumscribed hyperperfusion within the left mesial temporal lobe (ventral part of the hippocampus). Additionally an increase in perfusion could be seen within the entire remaining left temporal lobe. Semiquantitative evaluation of tracer uptake comparing both studies detected markedly increased uptake within the focus compared to the remaining left temporal lobe. On this basis the newly available tracer for studies of rCBF, 99mTc-bicisate, seems to be of value for the detection of epileptogenic foci. Additionally, the value of ictal rCBF studies in the presurgical evaluation of those patients presenting severe morphological alterations on MRI is clearly underlined by this case.