Jörn O. Balzer

Intraarterial Administration of Bone Marrow Mononuclear Cells in Patients With Critical Limb Ischemia A Randomized-Start, Placebo-Controlled Pilot Trial (PROVASA)

Background—Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking. Methods and Results—Forty patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC (open label) after 3 months. Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and, thus, the trial missed its primary end point. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2±4.7 cm2 to 1.89±3.5 cm2 [P=0.014] versus placebo, 2.92±3.5 cm2 to 2.89±4.1 cm2 [P=0.5]) and reduced rest pain (5.2±1.8 to 2.2±1.3 [P=0.009] versus placebo, 4.5±2.4 to 3.9±2.6 [P=0.3]) within 3 months. Limb salvage and amputation-free survival rates did not differ between the groups.Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage (r=0.8; P<0.001). Conclusions—Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation. These exploratory findings of this pilot trial need to be confirmed in a larger randomized trial in patients with critical limb ischemia and stable ulcers. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00282646.

Repeated Transarterial Chemoembolization in the Treatment of Liver Metastases of Colorectal Cancer: Prospective Study

PURPOSE To evaluate local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of liver metastases in patients with colorectal cancer. MATERIALS AND METHODS The study was approved by institutional review board, and informed consent was obtained from all patients included in the study. A total of 463 patients (mean age, 62.5 years; range, 34.7-88.1 years) with unresectable liver metastases of colorectal cancer that did not respond to systemic chemotherapy were repeatedly treated with chemoembolization in 4-week intervals. In total, 2441 chemoembolization procedures were performed (mean, 5.3 sessions per patient). Of 463 patients, 67.4% had multiple (five or more) metastases, 8% had one metastasis, 10.4% had two metastases, and 14.3% had three or four metastases. The local chemotherapy protocol consisted of mitomycin C alone (n = 243), mitomycin C with gemcitabine (n = 153), or mitomycin C with irinotecan (n = 67). Embolization was performed with lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated with magnetic resonance imaging. The change in tumor size was calculated and the response was evaluated according to the Response Evaluation Criteria in Solid Tumors. Survival rates from first diagnosis and from first chemoembolization session were calculated according to the Kaplan-Meier method. Follow-up imaging was performed until patient death. RESULTS Evaluation of local tumor control resulted in partial response (68 patients [14.7%]), stable disease (223 patients [48.2%]), and progressive disease (172 patients [37.1%]). The 1-year survival rate after chemoembolization was 62%, and the 2-year survival rate was 28%. Median survival from date of diagnosis of liver metastases was 38 months and from the start of chemoembolization treatment was 14 months. There was no statistically significant difference between the three treatment protocols. CONCLUSION Chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with colorectal cancer, with similar results among three chemoembolization protocols.

Intraarterial Administration of Bone Marrow Mononuclear Cells in Patients With Critical Limb IschemiaClinical Perspective

Background—Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking. Methods and Results—Forty patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC (open label) after 3 months. Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and, thus, the trial missed its primary end point. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2±4.7 cm2 to 1.89±3.5 cm2 [P=0.014] versus placebo, 2.92±3.5 cm2 to 2.89±4.1 cm2 [P=0.5]) and reduced rest pain (5.2±1.8 to 2.2±1.3 [P=0.009] versus placebo, 4.5±2.4 to 3.9±2.6 [P=0.3]) within 3 months. Limb salvage and amputation-free survival rates did not differ between the groups.Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage (r=0.8; P<0.001). Conclusions—Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation. These exploratory findings of this pilot trial need to be confirmed in a larger randomized trial in patients with critical limb ischemia and stable ulcers. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00282646.

Magnetic resonance imaging of focal liver lesions. Comparison of the superparamagnetic iron oxide resovist versus gadolinium-DTPA in the same patient

RATIONALE AND OBJECTIVES The authors assess the efficacy of static and dynamic magnetic resonance (MR) imaging using the superparamagnetic iron oxide SHU-555A (Resovist) versus standard dose of gadolinium (Gd)-DTPA in patients with focal liver lesions. METHODS Magnetic resonance imaging was performed in 30 patients suffering from histopathologically verified malignant (n = 22) and benign (n = 8) liver lesions. T2-weighted conventional and fat-suppressed as well as T1-weighted sequences were used before, during, and after fast intravenous administration of Resovist (1 mL/minute) at three doses of 4, 8, and 16 mumol/kg body weight. One week before the Resovist-enhanced MR imaging study 20 patients underwent Gd-DTPA-enhanced MR imaging. RESULTS Detection rate was improved for metastatic lesions revealing 36 lesions unenhanced versus 53 focal lesions using Resovist-enhanced MR imaging. Gadolinium-DTPA-enhanced scans showed no additional lesion versus unenhanced and Resovist-enhanced MR imaging. Static and dynamic imaging demonstrated no measurable percentage signal intensity loss (PSIL) using Resovist-enhanced MR imaging versus a percentage enhancement of 79.7% in Gd-DTPA enhanced scans. In the dynamic T2-weighted sequences, hepatocellular carcinoma nodules (n = 4) showed a rapid decrease in signal intensity starting at 44 seconds. Postinfusion of Resovist followed by a low, constant increase in signal intensity. Gadolinium-DTPA enhanced scans showed a percentage enhancement of 73.4 focal nodular hyperplasia (FNH) and hemangioma revealed a strong and early dose-dependent PSIL 44 to 60 seconds postinfusion with a prolonged signal loss for the FNH in the late study. Statistical evaluation revealed a statistically significant superiority of Resovist-enhanced MR imaging concerning the detection and delineation of focal liver lesions compared with unenhanced and Gd-DTPA enhanced scans (P < 0.05). CONCLUSIONS The fast infusion of the new superparamagnetic contrast agent Resovist shows advantages for dynamic and static MR imaging of focal liver lesions.

One-Year Outcome of Percutaneous Rotational Atherectomy with Aspiration in Infrainguinal Peripheral Arterial Occlusive Disease: The Multicenter Pathway PVD Trial

Purpose: To report a safety and efficacy study of a novel rotational atherectomy system with aspiration capabilities for the treatment of infrainguinal arterial lesions. Methods: From February 2006 to January 2007, 172 patients (88 women; mean age 72 years, range 51–93; 47% diabetics) with Rutherford class 1–5 lower limb ischemia were enrolled at 9 study sites. Inclusion criteria were atherosclerotic stenoses >70% and up to 10 cm long in the femoropopliteal segment or up to 3 cm long in the infrapopliteal vessels (reference vessel diameter 3.0–5.0 mm). In the study, 210 lesions (mean length 2.7 cm) were treated with the Pathway PV System, including total occlusions (31%), lesions with a moderate to high calcium score (51%), and post-angioplasty (non-stent) restenotic lesions (15%). The primary study endpoint was the 30-day major adverse event (MAE) rate. Results: Device success was 99% (208/210 lesions). MAE at 30 days was 1% (2 preplanned amputations). Clinically driven target lesion revascularization rates at 6 and 12 months were 15% (25/172) and 26% (42/162), respectively. The 1-year restenosis rate was 38.2% based on duplex imaging. The ankle-brachial index increased significantly from 0.59±0.21 at baseline to 0.82±0.27 (p<0.05) at 12 months. Mean Rutherford class improved from 3.0±0.9 at baseline to 1.5±1.3 at 1 year (p<0.05). Conclusion: The use of the Pathway PV System in atherosclerotic lesions appears to be safe and effective in improving stenosis severity, even in the presence of challenging lesion conditions. Vessel patency following intervention appears to be good up to 12 months, and these results translate into clinical benefit.

Percutaneous interventional reconstruction of the iliac arteries: primary and long-term success rate in selected TASC C and D lesions

We report the primary and long-term outcome of patients with selected TransAtlantic Inter-Society Consensus (TASC) C or D lesions of the iliac arteries after percutaneous interventional reconstruction. Between 1999 and 2001, 89 patients with peripheral arterial disease categorized as TASC C (n=37) and D (n=52) underwent percutaneous interventional reconstruction and stent implantation. Patients were followed for 1–62 months (mean 36 months). Patency rates were assessed by Duplex ultrasound and ankle–brachial index (ABI) measurement. The primary technical success rate was 96.9% with an overall complication rate of 5.6%. The ABI improved from an average of 0.51±0.15 before intervention to 0.79±0.16 on the day following intervention and to 0.81±0.17 within 3 years after intervention. Clinical improvement was observed in 97.3% of the patients in the TASC C group and in 88.5% in the TASC D group. Eighty of 89 patients (89.9%) remained patent at 3-year follow-up. In five patients the reintervention was successful. The secondary patency rate was 95.5%. The patency rates were similar in our selected TASC C and D patients to those so far published for TASC A and B, with low complication rates. Therefore, percutaneous intervention can be recommended for these patients.

Angioplasty of the pelvic and femoral arteries in PAOD: results and review of the literature.

PURPOSE Evaluation of percutaneous recanalization of obstructed iliac as well as superficial femoral arteries (SFAs) in patients with peripheral arterial obstructive disease (PAOD). MATERIAL AND METHODS The data of 195 consecutive patients with 285 obstructions of the common and or external iliac artery as well as the data of 452 consecutive patients with 602 long occlusions (length>5 cm) of the SFA were retrospectively analyzed. The lesions were either treated with percutaneous transluminal angioplasty (PTA) or Excimer laser assisted percutaneous transluminal angioplasty (LPTA). Overall 316 stents were implanted (Nitinol stents: 136; stainless steel stents: 180) in the iliac artery and 669 stents were implanted (Nitinol stents: 311; Easy Wallstents: 358) in the SFA. The follow-up period was 36-65 months (mean 46.98+/-7.11 months) postinterventionally using clinical examination, ABI calculation, and color-coded duplex sonography. Patency rates were calculated on the basis of the Kaplan-Meier analysis. RESULTS The overall primary technical success rate was 97.89% for the iliac arteries and 92.35% for the SFA. Minor complications (hematoma, distal emboli and vessel dissection) were documented in 11.79% for the iliac arteries and 7.97% for the SFA. The primary patency rate was 90.3% for the iliac and 52.8% for the SFA after 4 years. The secondary patency rate was 96.84% for the iliac and 77.8% for the SFA after 4 years. CONCLUSION Percutaneous recanalization of iliac and superficial femoral artery obstructions is a safe and effective technique for the treatment of patients with PAOD. By consequent clinical monitoring high secondary patency rates can be achieved. The use of a stents seems to result in higher patency rate especially in the SFA when compared to the literature in long-term follow-up.

Chronische Infektionen der Nasennebenhöhlen

ZusammenfassungZielsetzung. Evaluation des Stellenwerts der bildgebenden Diagnostik bei entzündlichen Erkrankungen der Nasennebenhöhlen. Material und Methoden. Die moderne Diagnostik der Nasennebenhöhlen beruht auf dem kombinierten Einsatz klinischer Untersuchungsverfahren sowie bildgebender radiologischer Techniken. Zum Einsatz kommen einmal die konventionelle Röntgendiagnostik mit Nasennebenhöhlenaufnahmen in o.m.- und o.f.-Orientierung, die A- und B-Bild-Sonographie, die Computertomographie sowie die Magnetresonanztomographie nativ und kontrastmittelverstärkt. Ergebnisse. Die Wertigkeit der konventionell röntgenologischen Nasennebenhöhlendiagnostik ist heute stark eingeschränkt. Indikationsbereiche umfassen die gezielte Fokussuche sowie die Fahndung nach Spiegelbildung bei der akuten Sinusitis. Für die Diagnostik chronisch entzündlicher Veränderungen hat die Computertomographie die höchste diagnostische Bedeutung. Im Falle komplett verschatteter Nasennebenhšhlen oder bei Verdacht auf Beteiligung der Frontobasis liefert die MRT wichtige diagnostische Zusatzinformationen. Schlussfolgerungen. Die bildgebende Diagnostik der Nasennebenhöhlen ist heute unverzichtbar zur Diagnostik chronischentzündlicher Veränderungen.AbstractPurpose. Evaluation of the clinical value of imaging techniques for chronic inflammatory disease of paranasal sinuses. Materials and methods. Beside clinical tests imaging of the paranasal sinuses is based on the techniques like conventional X-ray studies, ultrasound, computed tomography and magnetic resonance techniques. Results. The value of conventional X-ray is lowered and is today focused on the diagnosis of acute sinusitis with fluid level and the detection of inflammatory foci. Spiral-CT using transverse and coronal orientation or reformatted images is considered as the diagnostic method of choice for the majority of clinical questions. MRT allows additional diagnostic informations in completely obstructed maxillary sinuses and patients with suspected anterior skullbase involvement. Conclusion. Imaging techniques do provide substantial diagnostic informations in patients with chronic sinusitis.

German Multicenter Real-World Registry of Stenting for Superficial Femoral Artery Disease: Clinical Results and Predictive Factors for Revascularization

Purpose: To investigate nitinol stent treatment of superficial femoral artery (SFA) lesions and the impact of different risk factors on the need for clinically driven target lesion revascularization (TLR) in a large, real-world population of claudicants. Methods: Patients presenting with symptomatic SFA stenosis >70% were consecutively enrolled in the 13-center MARIS prospective registry (ClinicalTrials.gov identifier NCT01067885). There was no restriction on lesion length, thus leading to the inclusion of a real-world as well as high-risk patient cohort. The 998 participating patients (657 men; mean age 67.4±9.2 years) had 1050 lesions treated with the same nitinol stent type. The mean lesion length was 9.5±9.6 cm (range 0.5–44; median 8.0); more than a third of the lesions (450, 42.9%) were total occlusions. The primary endpoint was the need for clinically driven target lesion revascularization (TLR) at 12 months. Results: Acute technical success was achieved in 1042 (99.2%) lesions. Restenosis occurred in 187 (23.7%) and reocclusion in 79 (10.0%) lesions at 12 months. The primary endpoint of TLR at 12 months was reached by 136 (17.2%) patients. The periprocedural complication rate was 5.4%. Independent predictors of TLR were female gender [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.3 to 0.7, p<0.001] and lesion length >20 cm vs. 10 cm (OR 2.7, 95% CI 1.1 to 6.6, p=0.029) and 10–20 cm vs. 10 cm (OR 1.9, 95% CI 1.0 to 4.1, p=0.047). Conclusion: Stent implantation in the SFA is safe and associated with favorable acute and midterm results in a real-world setting. Lesion length and female gender were identified as independent risk factors for TLR.

One-Year Outcome After Percutaneous Rotational and Aspiration Atherectomy in Infrainguinal Arteries in Patient With and Without Type 2 Diabetes Mellitus

BACKGROUND To compare the safety and efficacy of a rotational aspiration atherectomy system (Jetstream) for the treatment of infrainguinal arteries in diabetic versus nondiabetic patients. METHODS A total of 172 patients with Rutherford stage 1-5 lower limb ischemia were treated with rotational aspiration atherectomy between February 2006 and February 2007. Of these, 80 patients with type 2 diabetes mellitus (DM: 46.5%) were compared with 92 nonDM (53.5%) patients. Overall, 210 target lesions (99 DM; 111 nonDM) were treated, located in the superficial femoral (67% DM; 61% nonDM), popliteal (25% DM; 30% nonDM), and tibial (8% DM; 9% nonDM) arteries. Lesion characteristics were comparable in both groups, mean lesion length was 28.5 mm (DM) and 26.2 mm (nonDM); total occlusions were present in 29% (DM) and 32% (nonDM), and 15% (DM) and 14% (nonDM) were restenotic. RESULTS In the entire cohort, device success was 99% (all but two lesions). The major adverse event (MAE) rate (death, index limb amputation, myocardial infarction, target lesion revascularization [TLR] and target vessel revascularization) in DM at 30 days was 2.5% (n = 2 planned amputations) and 0% in nonDM. At 6 and 12 months, MAE in DM was seen in 13.8% (11/80) and 25% (20/80) compared with 21.7% (20/92) and 31.5% (29/92) in nonDM, respectively. TLR rate through 12 months was 20% (16/80) in DM and 28% in nonDM (26/92). Overall, 1 year restenosis rate was 38.2% based on duplex. The ankle-brachial index, mean Rutherford categories, and walking impairment questionnaire did not differ between groups at baseline and were increased significantly in both study cohorts at 12 months. CONCLUSION Jetstream-assisted atherectomy in infrainguinal arteries is safe and effective in DM compared with nonDM patients. In this short-lesion cohort, vessel patency in diabetics was as good as for non-DM at 1 year. TLR and MAE were higher by trend in nonDM, although planned amputations were seen only in DM. The clinical benefit was similar in both groups.