PURPOSE:The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2-negative early breast cancer (EBC).PATIENTS AND METHODS:Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were eligible. High-risk pN0 was defined by one or more of the following: pT greater than 2, grade 2 to 3, high urokinase-type plasminogen activator/plasminogen activator inhibitor-1, hormone receptor (HR) negativity, and less than 35 years of age. After an early amendment, all HR-positive tumors underwent recurrence score (RS) testing, with chemotherapy omission recommended in RS less than or equal to 11 pN0 to pN1 disease. Patients were randomly assigned to four cycles of epirubicin (E)90/cyclophoshamide (C)600 followed by four cycles of docetaxel (T)100 or six cycles of T75C600 (administered once every 3 weeks). The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The protocol specified P = .05 for a noninferiority margin of 4.4% for all patients combined.RESULTS:Of the 3,198 registered patients, 348 (RS ≤ 11) omitted chemotherapy, and 401 were not randomly assigned. The intention-to-treat population included 2,449 patients (1,227 EC-T v 1,222 TC: postmenopausal, 62.2% v 60.8%; pN0, 58.2% v 59.5%; pT1, 57.6% v 52.3%; HR positive, 81.4% v 82.2%; RS greater than 25 [in HR-positive patients], 26.2% v 27.5%). Within the safety population (1,167 v 1,178 patients), 87.5% v 93.0% completed therapy. After a 60-month median follow-up, 5-year outcomes were similar in the EC-T and TC arms (DFS, 89.6% [95% CI, 87.9% to 91.5%] v 89.9% [95% CI, 88.1% to 91.8%]; OS, 94.5% [95% CI, 93.1% to 95.9%] v 94.7% [95% CI, 93.3% to 96.1%]). The DFS difference was within the noninferiority margin of the original trial design. Five treatment-related deaths were reported for TC (one for EC-T), despite a trend toward more-severe adverse events in the latter. Interaction analysis revealed no predictive trends with respect to key factors, including triple-negative, luminal A/B-like, pN, age, and RS status.CONCLUSION:In the West German Study Group PlanB trial, 5-year outcomes for TC and EC-T were equally excellent. Six cycles of TC is an effective/safe option in human epidermal growth factor receptor 2-negative EBC with pN0 high genomic risk or pN1 EBC with genomically intermediate- to high-risk disease.

This study evaluated graft patency and flow at rest/stress in patients with coronary artery bypass grafts using MR flow measurements and MR angiography (MRA). 45 symptomatic patients with 86 grafts (46 arterial, 40 venous) were examined 5.5 years after surgery. MRA was used to assess bypass patency. Flow measurements were performed at rest and after stress induction with dipyridamole. All graft segments were evaluated at MRA for stenosis, and were additionally evaluated by the combination of flow measurements and MRA. Conventional coronary angiography or multidetector computed tomography was regarded as a reference standard. No significant stenosis was observed in 49 grafts (Group A), whereas significant stenosis was observed in 37 grafts (Group B). Sensitivity, specificity, and positive and negative predictive values for stenosis in arterial grafts were 95.2%, 96.8%, 80% and 99.4%, respectively, and in venous grafts were 100%, 97.8%, 87.5% and 100%, respectively. The mean blood flow rate at baseline/stress in Group B was significantly lower than that in Group A (p<0.002/p<0.001). With the combined MR method, 84 of 86 (97%) grafts could be correctly classified. In conclusion, MRI allows a combined assessment of graft status, including bypass patency and flow, in symptomatic patients after revascularization.

Objectives: Milrinone has been shown to be effective in corrective surgery for congenital heart disease. Increase in cardiac output is thought to be caused by a combination of inotropy and reduction of systemic and pulmonary vascular resistance. The aim of this study was to evaluate the pure cardiac effects of milrinone in isolated hearts after cardioplegic cardiac arrest.

Ziele: Bestimmung der Bypass-Offenheit und der Flussvolumina in Ruhe und nach medikamentöser Stressbelastung bei Patienten mit erneuten pectanginösen Beschwerden nach operativer Myokardrevaskularisation. Methode: An einem 1.5T Magnetom Sonata (SIEMENS) wurden 45 symptomatische Patienten mit 86 grafts postoperativ untersucht. Zunächst erfolgte die Bypassdarstellung mittels einer Kontrastmittel verstärkten FLASH-3D MR Angiographie (0,02 mmol/kg/KG Gd-DTPA). Danach wurden Phasenkontrast Flussmessungen im Bypass in Ruhe und nach medikamentöser Stressbelastung mit 0,56mg/kg/KG Dipyridamol zur Bestimmung der Flussreserve durchgeführt. Die Ergebnisse wurden mit der selektiven Bypassangiographie (SBA) oder Multi-Detektor-CT-Angiographie (MDCTA) verglichen (Sensation 16, SIEMENS). Es erfolgte ein Segment-zu-Segment-Vergleich. Ergebnis: 49 Bypasses waren in der SBA/MDCTA offen und 37 stenosiert.

Aims: The use of Aprotinin in many surgical disciplines is increasing. Most reported anaphylactic reactions occurred within one moth after first exposure, often in patients reexposed to aprotinin after failed mitral valve repair, or patients being on ventricular assist device as bridge to transplant. The present study was designed to investigate the immunopathologic reactions during the first 100 days post exposure.

Purpose: To evaluate graft patency, flow and flow reserve in patients with minimal invasive direct coronary artery bypass (MIDCAB) of internal mammary artery (IMA) grafts using a combined MR protocol with phase-contrast technique and MR angiography. Material and Methods: At a 1.5T Magnetom Sonata (SIEMENS),19 symptomatic (angina CCS I-III, intermittent thoracic discomfort, scar disorders) patients (59.9 +/- 7.9 years old) with 19 left internal mammary artery (LIMA) grafts implanted in minimal invasive technique were examined 6.9 +/- 1.5 years post surgery. Contrast enhanced MR angiography (TR 2.5 ms, TE 1 ms, flip angle 20, spatial resolution 1.4 x 0.9 x 1.0 mm(3), breath hold technique, no ECG-triggering, 25 ml Gd-DTPA) was performed to assess bypass patency. Phase-contrast flow measurements with retrospective gating (TR 41 msec, TE 3.2 msec, flip angle 30, spatial resolution 1.1 x 1.1 x 5 mm3, temporal resolution 42 msec, venc 90 cm/sec) were applied in the IMA grafts at rest and after stress induction with dipyridamole (0.56 mg/kg/BW). For comparison, graft patency was evaluated by multidetector-row computed tomography (16-row CT). In 9 patients a selective catheter angiography was performed. Results: MIDCAB grafts were occluded in 4/19 patients. In 4 patients the anastomosis to LAD was highly stenotic (> 70%) at MDCT (2 experienced investigators in consensus reading). In MRA 9 grafts could be delineated completely including the distal anastomosis to LAD (47%). In 9 patients the distal part could not be evaluated. In patients with patent grafts (MDCT), a significant improvement of graft flow (at rest 75.4 +/- 33.3 ml/min; after stress 202.7 +/- 49.6; P < 0.002) and flow reserve (patent grafts +/- 1.1; stenotic grafts 1.5 +/- 0.2, P < 0.02; occluded grafts 0.9 +/- 0.2, P < 0.01) after stress induction was detected. Diastolic-to-systolic peak velocity ratios (D/S-PVR) at baseline were not significant between patent and stenotic grafts. Mean flow at baseline and after stress induction and flow reserve show a high sensitivity (91/92/83%) and specificity (86/100/83%) for detection of graft stenosis. MR angiography combined with flow reserve measurements could distinguish between occluded/stenotic and patent grafts in all MIDCAB grafts. Conclusion: MR imaging allows combined assessment of bypass patency and flow with flow reserve in patients after MIDCAB. The protocol of this study is applicable for the evaluation of graft patency in patients after revascularization.

Objectives: We sought to evaluate graft patency, flow, and flow reserve in patients with minimally invasive direct coronary artery bypass surgery of internal thoracic artery grafts by a combined magnetic resonance protocol with a phase-contrast technique and magnetic resonance angiography.Methods: At 1.5 T (Magnetom Sonata, Siemens), 30 symptomatic patients with 30 left internal thoracic artery grafts were examined 6 years after minimally invasive surgical intervention. Navigator-gated magnetic resonance angiography and contrast-enhanced FLASH-3D magnetic resonance angiography (0.2 mmol gadopentate-diethylene tri-amine pentetic acid [Gd-DTPA]/kg body weight) was used to assess bypass patency. Phase-contrast flow measurements with retrospective gating were performed in the internal thoracic artery grafts at rest and after stress induction with dipyridamole (0.57 mg/kg body weight). Graft patency was evaluated by means of multidetector computed tomography (Sensation 16, Siemens).Results: internal thoracic artery grafts were occluded in 5 of 30 patients. In 6 patients the anastomosis to the left anterior descending artery was highly stenotic (>70%) at multidetector compled tomography. In patients with regular grafts (multidetector computed tomography), a significant improvement of graft flow (P < .001) and diastolic/systolic peak velocity ratio (P < .001) after stress induction was detected. Magnetic resonance angiography combined with flow reserve measurements Could differentiate between occluded-stenotic and regular minimally invasive direct coronary artery bypass grafts.Conclusions: Magnetic resonance imaging allows a combined assessment of bypass patency and flow with flow reserve in patients after the minimally invasive direct corollary artery bypass operation. The protocol of this study might be applicable for the evaluation of graft status in symptomatic patients after revascularization.

Ziele: Bestimmung der Flussreserve und Offenheit bei Patienten nach minimalinvasiver linksseitiger Mammaria Interna Bypass-Operation (MIDCAB) im Vergleich zur Multidetektor-CT-Angiographie. Methode: An einem 1.5T Magnetom Sonata (SIEMENS) wurden 34 symptomatische Patienten mit 34 Linke Mammaria Interna (LIMA) grafts in minimalinvasiver Technik 6 Jahre postoperativ untersucht. Zunächst erfolgte die Bypassdarstellung mittels einer Kontrastmittel verstärkten FLASH-3D MR-Angiographie (0,02 mmol/kg/KG Gd-DTPA). Danach wurden Phasenkontrast Flussmessungen im Bypass in Ruhe und nach medikamentöser Stressbelastung mit 0,56mg/kg/KG Dipyridamol zur Bestimmung der Flussreserve durchgeführt. Die Ergebnisse wurden mit der Multi-Detektor-CT-Angiographie verglichen (Sensation 16, SIEMENS). Ergebnis: In 21/34 Patienten waren die Bypasses im MDCT offen. Bei diesen Patienten konnte ein signifikanter Flussanstieg (p<0,001)und ein Anstieg der Diastolisch-zu-systolischen Peak (p<0,01) nach medikamentöser Stressbelastung gemessen werden. 6/34 LIMA grafts waren sowohl im CT als auch im MRT verschlossen. Bei 7 Patienten waren im CT die distale Anastomose zum RIVA höhergradig stenosiert. Bei diesen Patienten wurde im Vergleich zu den offenen Bypasses ein deutlich niedrigerer Fluss und Flussreserve in den grafts gemessen. Schlussfolgerung: Mit dem vorgestellten kombinierten Untersuchungsprotokoll ist es möglich die Offenheit, sowie den Fluss und Flussresereve in den Bypasses bei symptomatischen Patienten nach MIDCAB-Op zu bestimmen. Die Detektion hämodynamisch relevanter Stenosen gelang bei allen 7 Patienten, bei denen im CT eine Stenose im Bypass nachgewiesen wurde.

PURPOSE:To evaluate graft patency, flow and flow reserve in patients with minimal invasive direct coronary artery bypass (MIDCAB) of internal mammary artery (IMA) grafts using a combined MR protocol with phase-contrast technique and MR angiography.MATERIAL AND METHODS:At a 1.5T Magnetom Sonata (SIEMENS), 19 symptomatic (angina CCS I-III, intermittent thoracic discomfort, scar disorders) patients (59.9 +/- 7.9 years old) with 19 left internal mammary artery (LIMA) grafts implanted in minimal invasive technique were examined 6.9 +/- 1.5 years post surgery. Contrast enhanced MR angiography (TR 2.5 ms, TE 1 ms, flip angle 20 (o), spatial resolution 1.4 x 0.9 x 1.0 mm(3), breath hold technique, no ECG-triggering, 25 ml Gd-DTPA) was performed to assess bypass patency. Phase-contrast flow measurements with retrospective gating (TR 41 msec, TE 3.2 msec, flip angle 30 degrees , spatial resolution 1.1 x 1.1 x 5 mm(3), temporal resolution 42 msec, venc 90 cm/sec) were applied in the IMA grafts at rest and after stress induction with dipyridamole (0.56 mg/kg/BW). For comparison, graft patency was evaluated by multidetector-row computed tomography (16-row CT). In 9 patients a selective catheter angiography was performed.RESULTS:MIDCAB grafts were occluded in 4/19 patients. In 4 patients the anastomosis to LAD was highly stenotic (> 70 %) at MDCT (2 experienced investigators in consensus reading). In MRA 9 grafts could be delineated completely including the distal anastomosis to LAD (47 %). In 9 patients the distal part could not be evaluated. In patients with patent grafts (MDCT), a significant improvement of graft flow (at rest 75.4 +/- 33.3 ml/min; after stress 202.7 +/- 49.6; P < 0.002) and flow reserve (patent grafts 3.0 +/- 1.1; stenotic grafts 1.5 +/- 0.2, P < 0.02; occluded grafts 0.9 +/- 0.2, P < 0.01) after stress induction was detected. Diastolic-to-systolic peak velocity ratios (D/S-PVR) at baseline were not significant between patent and stenotic grafts. Mean flow at baseline and after stress induction and flow reserve show a high sensitivity (91/92 /83 %) and specificity (86 /100/83 %) for detection of graft stenosis. MR angiography combined with flow reserve measurements could distinguish between occluded/stenotic and patent grafts in all MIDCAB grafts.CONCLUSION:MR imaging allows combined assessment of bypass patency and flow with flow reserve in patients after MIDCAB. The protocol of this study is applicable for the evaluation of graft patency in patients after revascularization.

Ziele: Bestimmung der Flussreserve und Offenheit bei symptomatischen Patienten nach minimal invasiver linksseitiger Mammaria Interna Bypass-Operation (MIDCAB) im Vergleich zur Multidetektor-CT-Angiographie. Methode: An einem 1,5T Magnetom Sonata (SIEMENS) wurden 22 symptomatische Patienten mit 22 linke Mammaria Interna Bypasses in MIDCAB-Technik 6 Jahre postoperativ untersucht. Zunächst erfolgte die Bypassdarstellung mittels einer Kontrastmittel verstärkten FLASH-3D MR Angiographie (25ml Gd-DTPA). Danach wurden Phasenkontrast Flussmessungen im Bypass in Ruhe und nach medikamentöser Stressbelastung mit 0,56mg/kg/KG Dipyridamol zur Bestimmung der Flussreserve durchgeführt. Die Ergebnisse wurden mit der Multi-Detektor-CT-Angiographie verglichen (Sensation 16, SIEMENS). Ergebnis: In 16/22 Patienten waren die Bypasses im MDCT offen. Bei diesen Patienten konnte ein signifikanter Flussanstieg (p<0,00002) und ein Anstieg der Diastolisch-zu-systolischen Peaks (p<0,01) nach medikamentöser Stressbelastung gemessen werden. 3/22 LIMA grafts waren sowohl im MR als auch im CT verschlossen. Bei 3 Patienten waren im CT die distale Anastomose zum RIVA höhergradig stenosiert. Bei diesen Patienten wurde im Vergleich zu den offenen Bypasses ein deutlich niedrigerer Fluss und Flussreserve in den grafts gemessen. Schlussfolgerung: Mit dem vorgestellten kombinierten Untersuchungsprotokoll ist es möglich, die Offenheit, sowie den Fluss und die Flussreserve in den Bypasses bei symptomatischen Patienten nach MIDCAB-Op zu bestimmen. Die Detektion hämodynamisch relevanter Stenosen gelang mit der MRT bei allen 3 Patienten, bei denen im CT eine Stenose im Bypass nachgewiesen wurde.

Purpose: The aim of this review is to present the current state of clinical oncological research on mistletoe extracts standardised in terms of the active substance mistletoe lectin. Methods: This review focuses on studies with clearly defined mistletoe extracts standardised in terms of mistletoe lectins I, II, and III (calculated as mistletoe lectin I, ML I) which belong to the category of rational phytotherapy. That means that studies with anthroposophic or homeopathic drugs will not be included. Results: There are several preclinical studies that show a cytotoxic and immunostimulating effect of mistletoe extracts, predominantly on the cellular immune system. The clinical database, however, is not as good as the experimental results. So far, no direct anticancer action or any improvement in time to tumour progression or overall survival in cancer patients has been seen. The first results of a randomised phase III study suggest that additive administration of a mistletoe preparation may improve the quality of life. Conclusion: Mistletoe therapy has not gained an established place in oncology. Further, well-planned randomised clinical investigations will be necessary to verify the first positive findings with regard to an improvement of quality of life in cancer patients.

European Society of Anaesthesiologists; 8th Annual Meeting with the Austrian International Congress; Vienna, Austria, 1-4 April 2000