Klaus Brechtel

Sirolimus-eluting stents vs. bare-metal stents for treatment of focal lesions in infrapopliteal arteries: a double-blind, multi-centre, randomized clinical trial

AIMS Preliminary reports indicate that sirolimus-eluting stents reduce the risk of restenosis after percutaneous infrapopliteal artery revascularization. We conducted a prospective, randomized, multi-centre, double-blind trial comparing a polymer-free sirolimus-eluting stent with a placebo-coated bare-metal stent in patients with either intermittent claudication or critical limb ischaemia who had a de-novo lesion in an infrapopliteal artery. METHODS AND RESULTS 161 patients were included in this trial. The mean target lesion length was 31 ± 9 mm. The main study endpoint was the 1-year primary patency rate, defined as freedom from in-stent-restenosis (luminal narrowing of ≥50%) detected with duplex ultrasound if not appropriate with angiography. Secondary endpoints included the 6-month primary patency rate, secondary patency rate, and changes in Rutherford-Becker classification after 1 year. Twenty-five (15.5%) patients died during the follow-up period. One hundred and twenty-five patients reached the 1-year examinations. The 1-year primary patency rate was significantly higher in the sirolimus-eluting stent group (80.6%) than in the bare-metal stent group (55.6%, P= 0.004), and the 1-year secondary patency rates were 91.9 and 71.4% (P= 0.005), respectively. The median (interquartile range) change in Rutherford-Becker classification after 1 year was -2 (-3 to -1) in the sirolimus-eluting stent group and -1 (-2 to 0) in the bare-metal stent group, respectively (P= 0.004). CONCLUSION Mid-term patency rates of focal infrapopliteal lesions are substantially improved with sirolimus-eluting stent compared with bare-metal stent. Corresponding to the technical results, the changes in Rutherford-Becker classification reveal a significant advantage for the sirolimus-eluting stent.

Fast elevation of the intramyocellular lipid content in the presence of circulating free fatty acids and hyperinsulinemia: a dynamic 1H-MRS study.

The influence of a short‐term elevation of free fatty acids (FFAs) on intramyocellular lipids (IMCL) under hyperinsulinemic conditions was monitored in five healthy male subjects in the course of a 5‐hr hyperinsulinemic glucose clamp. During the glucose clamp a lipid emulsion (Intralipid 20®) and heparin were administered intravenously. IMCL was quantified in the tibialis anterior (TA) and the soleus (SOL) muscle by 1H‐MRS. A rapid elevation of the IMCL pool was found in both muscles (61% in TA and 22% in SOL) in the 5‐hr time period. A control hyperinsulinemic glucose clamp in the same study group, repeated without elevation of circulating FFAs, did not lead to significant changes in IMCL for both muscles. The present study shows for the first time that only the combination of high concentrations of FFAs and insulin lead to marked storage of lipids in skeletal muscle cells in humans. Magn Reson Med 45:179–183, 2001.

MRI of muscular fat

An MRI technique with high selectivity and sensitivity to the signal components in the chemical shift range of methylene and methyl protons of fatty acids has been developed for noninvasive assessment of muscular fat in vivo. A spoiled gradient‐echo sequence with spatial‐spectral excitation by six equidistant pulses with 2°‐(−9°)‐17°‐(−17°)‐9°‐(−2°) and a multi‐echo train (TE = 16, 36, 56, 76, 96, and 116 ms) allowed a series of images to be recorded with a receiver bandwidth of 78 Hz per pixel. SIs from phantoms with lipid contents between 0.1% and 100% were compared to those from pure water. Thirty healthy volunteers underwent fat‐selective imaging of their lower leg, and parallel localized proton spectroscopy of the tibialis anterior and the soleus muscle by a single‐voxel stimulated echo acquisition mode (STEAM) technique (TR = 2 s, TE = 10 ms, TM = 15 ms). Results show a high correlation (r = 0.91) between fat imaging and the spectroscopic approach in the soleus muscle, considering the percentage total fat content of musculature. The correlation coefficient was clearly lower (r = 0.55) in the tibialis anterior muscle due to signal contaminations from adjacent subcutaneous fat in the images, inhomogeneous fat distribution, and generally lower lipid content in this muscle. Applications of the new imaging technique showed marked intra‐ and interindividual variability in the spatial distribution of lipids in the musculature of the lower leg. No significant correlation of the muscular fat with the thickness of the subcutaneous fat layer was found. In addition, the body mass index does not appear to determine muscular fat content, except in very obese cases. Magn Reson Med 47:720–727, 2002.

Sirolimus-eluting stents for treatment of infrapopliteal arteries reduce clinical event rate compared to bare-metal stents: long-term results from a randomized trial.

OBJECTIVES The study investigated the long-term clinical impact of sirolimus-eluting stents (SES) in comparison with bare-metal stents (BMS) in treatment of focal infrapopliteal lesions. BACKGROUND There is evidence that SES reduce the risk of restenosis after percutaneous infrapopliteal artery revascularization. No data from randomized trials are available concerning the clinical impact of this finding during long-term follow-up. METHODS The study extended the follow-up period of a prospective, randomized, multicenter, double-blind trial comparing polymer-free SES with placebo-coated BMS in the treatment of focal infrapopliteal de novo lesions. The main study endpoint was the event-free survival rate defined as freedom from target limb amputation, target vessel revascularization, myocardial infarction, and death. Secondary endpoints include amputation rates, target vessel revascularization, and changes in Rutherford-Becker class. RESULTS The trial included 161 patients. The mean target lesion length was 31 ± 9 mm. Thirty-five (23.3%) patients died during a mean follow-up period of 1,016 ± 132 days. The event-free survival rate was 65.8% in the SES group and 44.6% in the BMS group (log-rank p = 0.02). Amputation rates were 2.6% and 12.2% (p = 0.03), and target vessel revascularization rates were 9.2% and 20% (p = 0.06), respectively. The median (interquartile range) improvement in Rutherford-Becker class was -2 (-3 to -1) in the SES group and -1 (-2 to 0) in the BMS group, respectively (p = 0.006). CONCLUSIONS Long-term event-free survival, amputation rates, and changes in Rutherford-Becker class after treatment of focal infrapopliteal lesions are significantly improved with SES in comparison with BMS. (YUKON-Drug-Eluting Stent Below the Knee-Randomised Double-Blind Study [YUKON-BTX]; NCT00664963).

Angioplasty of Femoral-Popliteal Arteries With Drug-Coated Balloons: 5-Year Follow-Up of the THUNDER Trial

OBJECTIVES The purpose of this study was to evaluate the 5-year follow-up (FU) data of the THUNDER (Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries). BACKGROUND The THUNDER trial was the first study to investigate the treatment of femoropopliteal arteries with a paclitaxel-coated balloon (PCB). METHODS In 154 patients, femoropopliteal arteries were treated with PCB, with angioplasty with paclitaxel in contrast medium, or no paclitaxel (control). The primary endpoint was 6-month late lumen loss (LLL). Secondary endpoints included freedom from target lesion revascularization (TLR), binary restenosis rate, and amputation. The 5-year FU compares outcomes in patients treated with PCB and control subjects. Additionally, LLL at 6 months and TLR up to 5-year FU were analyzed in terms of sex and lesion length. RESULTS Over the 5-year period, the cumulative number of patients with TLR remained significantly lower in the PCB group (21%) than in the control group (56%, p = 0.0005). In the small group of patients with angiographic and duplex sonographic follow-up, PCB was associated with a lower rate of binary restenosis (17% vs. 54%; p = 0.04). No signs of aneurysm formation or constrictive fibrosis were detected. Whereas LLL at 6-month FU did not differ between men and women in the PCB group, the TLR rate was lower in men than in women at 5-year FU. A benefit of PCB treatment in terms of LLL and TLR was seen independent of lesion length. CONCLUSIONS The reduced TLR rate following PCB treatment was maintained over the 5-year FU period. No signs of drug-related local vessel abnormalities were detected. (Thunder Trial-Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries [THUNDER]; NCT00156624).

Treatment of femoropopliteal in-stent restenosis with paclitaxel-eluting stents.

OBJECTIVES This study sought to evaluate the outcomes of drug-eluting stent treatment for femoropopliteal in-stent restenosis (ISR). BACKGROUND ISR after femoropopliteal interventions is an increasing problem. Although the role of drug-eluting stents in the treatment of coronary ISR is well defined, no published studies have examined drug-eluting stents in the treatment of femoropopliteal ISR. METHODS This study examines 108 patients with 119 ISR lesions who were enrolled in the ZILVER-PTX single-arm study, a prospective, multicenter clinical trial of 787 patients. All patients were treated with paclitaxel-eluting nitinol stents. RESULTS Mean patient age was 68.3 ± 9.4 years; 61.1% of patients were men. Mean lesion length was 133.0 ± 91.7 mm; 33.6% of lesions were >150 mm long and 31.1% of lesions were totally occluded. Procedural success was achieved in 98.2% of lesions with 2.1 ± 1.2 stents placed per lesion. Primary patency was 95.7% at 6 months and 78.8% at 1 year. Freedom from target lesion revascularization was 96.2% at 6 months, 81.0% at 1 year, and 60.8% at 2 years. Forty patients experienced major adverse events, exclusively target lesion revascularization. Before treatment, 81.1% of patients had Rutherford scores ≥3; at 2 years, 60.9% of patients had Rutherford scores ≤1. Both ankle brachial index and walking impairment questionnaire scores significantly improved following treatment. The 1-year fracture rate of stents used in ISR lesions was 1.2%. No significant risk factors associated with loss of patency were identified. CONCLUSIONS Treatment of femoropopliteal ISR with paclitaxel-eluting stents results in favorable acute, midterm, and long-term outcomes. (Zilver PTX Global Registry [ZILVER-PTX]; NCT01094678).

Lipid content in the musculature of the lower leg assessed by fat selective MRI: Intra‐ and interindividual differences and correlation with anthropometric and metabolic data

To assess the muscular lipid content (LC) in different muscle groups of the lower leg by a magnetic resonance imaging technique working with chemical shift selective excitation, and comparison with anthropometric and metabolic data.

PET/CT for the assessment and quantification of 90Y biodistribution after selective internal radiotherapy (SIRT) of liver metastases

Dear Sir, We read with great interest the recently published Image of the Month by Lhommel et al. “Yttrium-90 TOF PET scan demonstrates high-resolution biodistribution after liver SIRT” [1]. The authors used a high-end time-of-flight (TOF) PET/CT in order to detect the annihilation photons that occur after internal pair formation in Y [2–4]. The authors show that Y PET/CT is feasible and potentially yields a better spatial resolution than bremsstrahlung scintigraphy or SPECT typically used for the evaluation of Y biodistribution after selective internal radiotherapy (SIRT) [5]. The authors used a 2.5-mm copper ring to prevent saturation of the PET detectors arising from the bremsstrahlung photons. In our department we had initiated similar measurements albeit with a non-TOF PET/CT (biograph Hi-Rez 16, Siemens Healthcare, Erlangen, Germany). Our results indicate that, in addition to the findings of Lhommel et al., Y PET/CT can be performed even without an advanced TOF mode (Fig. 1a). Saturation of the detectors did not seem to be an issue with our scanner, so an additional shielding of Y bremsstrahlung with a copper ring was not essential. We would like to add to the results presented by Lhommel and colleagues data from phantom studies performed using an International Electrotechnical Commission (IEC) hotsphere phantom with a Y concentration of 3.6 MBq/ml and an acquisition time of 40 min/bed position (Fig. 1c). Our studies using non-TOF PET/CT with 4×4 mm lutetium oxyorthosilicate (LSO) detector elements revealed a recovery coefficient (RC) of 0.6–1.0 with spheres 17 mm or larger in diameter. Recovery increased with the sphere diameter (Fig. 1d). Assuming a hot background (healthy liver tissue receiving a minor Y dose), a lesion size of approximately 17 mm seems to be the limit for reliable detectability with our PET/CT system. Using ordered subset expectation maximization (OSEM) reconstruction, a resolution of 5.2±0.6 mm (336×336 matrix, 8 iterations, 16 subsets) and 7.8±0.5 mm (128×128 matrix, 4 iterations, 8 subsets) was achieved. Our studies suggest a minimum concentration of 1MBq/ml of Y for PET imaging, which is easily obtained in SIRT. The sensitivity for Y PET is reduced by a factor of 3.4e-5 in comparison to F PET. Although bremsstrahlung scans (Fig. 1b) will probably remain the method of choice for the assessment of Y biodistribution in most applications, PET/ CT is possible in cases of sufficient radioactivity concentration in the target tissue as achieved in SIRT. Y PET/CT could become a versatile adjunct as we see combined PET/ M. K. Werner (*) :K. Brechtel :C. Pfannenberg Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Medical Center, Tübingen, Germany e-mail: Matthias.Werner@med.uni-tuebingen.de

First Experiences of Radiation Treatment Planning with PET/CT

Background:Positron emission tomography/computed tomography (PET/CT) is composed of modern CT and PET technology in one machine enabling examinations of patients in one session in the same position. Its value for modern radiation treatment planning is under investigation.Methods:In 53 patients with head-and-neck (n = 11), non-small cell lung (n = 16), prostate (n = 14) and other cancers (n = 12), a PET/CT investigation was performed. During the diagnostic examination process an integrated scan under radiation treatment-planning conditions was included. Interpretation and delineation of macroscopic tumor were done in an interdisciplinary approach. Treatment changes occurred after critical interpretation of the PET/CT findings by the responsible radiotherapist. Analysis is descriptive with regard to changes in treatment intention, mode, radiation volumes and doses.Results:Examinations were well tolerated. CT datasets in treatment position could be used for planning. Delineation of macroscopic tumor led to changes of the planning target volume after PET/CT 15 times, total dose was modified twelve times. PET/CT examinations led to changes of the general treatment mode in 19 cases. Using the separate CT and PET datasets, fusion in the planning software was easily performed in all patients due to the use of the same positioning and immobilization devices in PET/CT.Conclusion:Despite the low number of patients and an expectable bias of selection, the first results are encouraging to perform more extended and detailed trials of this technology in radiotherapy planning. Whether PET/CT is superior to PET alone is part of ongoing investigations.Hintergrund:Die Positronenemissionstomographie/Computertomographie (PET/CT) ist eine Weiterentwicklung der Einzelkomponenten moderner CT- und PET-Technologie in einer kombinierten Hybridmaschine, die eine Untersuchung in einer Sitzung in derselben Position ermöglicht. Die Bedeutung für die moderne Strahlentherapie wird intensiv erforscht.Methodik:Bei 53 Patienten mit fortgeschrittenen Kopf-Hals- (n = 11), nichtkleinzelligen Bronchial- (n = 16) und Prostatakarzinomen (n = 14) sowie anderen Tumoren (n = 12) wurde eine PET/CT durchgeführt. Während der diagnostischen Untersuchung wurden die Patienten in Bestrahlungsposition gelagert und ein Scan zur Bestrahlungsplanung integriert. Die Interpretation und Einzeichnung makroskopischen Tumors wurden in einem interdisziplinären Ansatz aus erfahrenem Strahlentherapeut, Nuklearmediziner und radiologischem Diagnostiker vollzogen. Änderungen der Behandlung wurden eingeleitet, wenn sich nach kritischer klinischer Abschätzung der PET/CT-Ergebnisse relevante neue Befunde ergaben. Die Analyse ist deskriptiv in Bezug auf Änderungen von Behandlungsmodalität, -intention, Bestrahlungsvolumen und -dosis.Ergebnisse:Die Untersuchungen mit der PET/CT wurden von den Patienten gut toleriert. Die CT-Datensätze in Behandlungsposition konnten für die Planung verwendet werden. Die Einzeichnung des makroskopischen Tumors führte nach 15 Untersuchungen (26%) zu Änderungen des Planungszielvolumens. Die Gesamtdosis wurde nach zwölf PET/CT-Untersuchungen (21%) modifiziert. PET/CT führte 19-mal (33%) zu Änderungen des generellen Behandlungsmodus. Die separaten CT- und PET-Datensätze der Patienten in derselben Position mit denselben Immobilisierungshilfen konnten zur Fusion in der Planungssoftware einfach genutzt werden.Schlussfolgerung:Trotz der relativ niedrigen Patientenzahl und eines möglichen Selektionsfehlers sind die ersten Ergebnisse erfolgversprechend, um weitere, ausgedehntere Untersuchungen mit großen Patientenzahlen durchzuführen. Inwieweit die kombinierte PET/CT den Einzelkomponenten mit späterer Fusion überlegen ist, sollte in diesem Zusammenhang evaluiert werden.

Endovascular Aneurysm Repair Using a Reverse Chimney Technique in a Patient With Marfan Syndrome and Contained Ruptured Chronic Type B Dissection

We report endovascular thoracic and abdominal aneurysm repair (EVAR) with reverse chimney technique in a patient with contained ruptured type B dissection. EVAR seems feasible as a bailout option in Marfan patients with acute life-threatening disease.