Heiko Alfke

Transarterial Chemoembolization of Advanced Liver Metastases of Neuroendocrine Tumors – A Retrospective Single-Center Analysis

Background: In neuroendocrine tumors, metastases are a negative prognostic factor for survival and quality of life. Transcatheter arterial chemoembolization (TACE) is thought to be an effective symptomatic and antiproliferative treatment in patients with otherwise progressive disease. Methods: 62 chemoembolization procedures in 26 patients with progressive neuroendocrine tumors were reviewed. The underlying disease was carcinoid syndrome in 10, non-functional midgut tumor in 2, non-functional pancreatic tumor in 7, malignant insulinoma in 2 patients, non-functional tumor of the stomach in 1 and of unknown origin in 4 patients. Tumor burden of the liver was <25% in 3, 25–50% in 11, 50–75% in 6 and >75% in 6 patients. Results: TACE was technically successful in 57 cases. Four patients developed minor and 5 major complications. The 30-day mortality rate was 7.7%. According to WHO criteria, 14 patients had no change in tumor burden, 2 had regression and 5 progress after chemoembolization. Patients with a tumor burden >75% of the liver did not benefit from TACE due to the development of major complications, whereas patients with low (<50%) tumor burden and high (>50%) lipiodol uptake showed a trend towards longer survival. Five-year survival time after diagnosis was 48%. Patients treated with octreotide and/or α-interferon had no benefit from chemoembolization with regard to their carcinoid syndrome. Conclusions: In this retrospective study, patients with low (<50%) tumor burden and high (>50%) lipiodol uptake responded better to TACE than end-stage patients.

Deposition of nanoparticles in the arterial vessel by porous balloon catheters: Localization by confocal laser scanning microscopy and transmission electron microscopy

Restenosis remains the major limitation of percutaneous transluminal angloplasty (PTA) and stenting in the treatment of patients with atherosclerotic disease. Catheter-based local delivery of pharmacologic agents offers a potential therapeutic approach to reducing restenosis and minimizing undesirable systemic side effects. However, the intramural retention of liquid agents is low. Therefore, to achieve a sustained and regional release of the therapeutic agent it must be encapsulated in nanoparticle carrier systems. The purpose of this study was to investigate the size dependence of the penetration of nanoparticles after local delivery into the vessel wall of the aorta abdominalis of New Zealand white rabbits. Two milliliters of a 0.025% fluorescence-labeled polystyrene nanoparticle suspension with diameters ranging from 110 to 514 nm were infused at 2 atm and at constant PTA pressure of 8 atm into the aorta abdominalis. After the infused segments were removed, the location of nanoparticles was visualized using confocal laser scanning microscopy and transmission electron microscopy. The study demonstrates a size-dependent nanoparticle penetration into the intact vessel wall. While nanoparticles of about 100 and 200 nm were deposited in the inner regions of the vessel wall, 514-nm nanoparticles accumulated primarily at the luminal surgace of the aorta. The observations confirm that size plays a critical role in the distribution of particles in the arterial vessel wall. It is additionally influenced by the formation of pressure-induced infusion channels, as well as by the existence of anatomic barriers, such as plaques, at the luminal surface of the aorta or the connective elastic tissue.

Paclitaxel inhibits proliferation of cell lines responsible for metal stent obstruction: possible topical application in malignant bile duct obstructions.

Kalinowski M, Alfke H, Kleb B, et al. Paclitaxel inhibits proliferation of cell lines responsible for metal stent obstruction - possible topical application in malignant bile duct obstructions: paclitaxel inhibits proliferation of gallbladder epithelium. Invest Radiol 2002;37:399–404. rationale and objectives. To evaluate a dose dependent inhibitory effect of paclitaxel to assess a possible local application for biliary tract malignancies in conjunction with stent placement. methods. Cell cultures of the three different cell types (human epithelial gallbladder cells [HEGC], human fibroblasts [HF; PA 314 wt] and pancreatic carcinoma cells [PC; P181]) were incubated for 20 minutes at 37°C with increasing doses of paclitaxel (1.0 × 10−4 − 1.0 × 102 &mgr;mol). Half of the cultures were then incubated without paclitaxel, the other half with paclitaxel for 20 minutes, 24 hours, or 72 hours. Cell proliferation was detected by photometric measurements of mitochondrial dehydrogenase activity (MTT assay). results. Incubation of cell cultures with paclitaxel resulted in a dose dependent and cell specific inhibition of cell proliferation. Concentrations of 1.0 × 10−4 (and higher) paclitaxel for 20 minutes resulted in a inhibition of cell proliferation of HEGC (28%), PA (26%), and HF (17%). A prolonged paclitaxel incubation (up to 72 hours) resulted in an inhibitory effect on cell proliferation of HEGC (40%), PA (45%), and HF (39%). Cytotoxic effects, manifested by development of vacuoles and damage of cell integrity were seen at concentrations above 1.0 × 101 for both the short and long term incubation. conclusions. Paclitaxel incubation resulted in a dose dependent inhibition of cell proliferation of human epithelial gallbladder cells, human fibroblasts and pancreatic carcinoma cells. This inhibitory effect of paclitaxel on the cell lines could serve as the basis to develop drug coated or drug eluting stents for malignant biliary strictures.

Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo

PurposeThere is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects.MethodsBiodistribution studies and in vivo therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of 131I and 99mTc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, 99mTc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration.ResultsNIS-expressing neuroendocrine tumors strongly accumulated 131I and 99mTc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of 131I or 99mTc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of 99mTc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of 99mTc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons.ConclusionsNIS-expressing neuroendocrine tumors efficiently concentrate radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful radioisotope therapy of neuroendocrine tumors.

Influence of somatostatin receptor scintigraphy and CT/MRI on the clinical management of patients with gastrointestinal neuroendocrine tumors: an analysis in 188 patients.

Aim: Many studies describe the sensitivities and specificities of computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT). We performed a study to evaluate the influence of these techniques on the therapeutic management of patients with advanced stages of GNT. Patients and Methods: The results of either CT/MRI scans or SRS were reviewed by two independent observers who decided on the therapy of a patient. They then had to determine whether the results of the complementary imaging modality would change the decision. The study design was a matched cross-over study with two groups matching in respect to tumor type, imaging modality known first to the observer, and number of patients. For further analysis, patients were divided into three subgroups dependent on tumor stage (group 1, without metastases, group 2, liver metastases, group 3, recurrent disease/extrahepatic metastases). Results: 188 patients were included into the study. If SRS was known to the observers first, CT/MRI changed the therapeutic management in 16.2, 13.9 and 11.4% of the patients (subgroups 1–3). SRS changed the therapeutic management in 13.5, 12.5 and 10.3%. Overall, CT/MRI would have changed the management in 13.3% and SRS in 11.7% of the patients. Conclusion: Though the patients studied mainly suffered from already advanced stages of the disease, all imaging techniques change the therapeutic management to a comparable extent. Our results support the importance of combined imaging in the management of patients with GNT.

The value of screening for multiple arterio-venous malformations in hereditary hemorrhagic telangiectasia: a diagnostic study

Occult visceral arterio-venous malformations (AVMs) may be a constant threat to patients suffering from hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome (M. ROW). HHT patients predominantly become symptomatic through chronic, recurrent epistaxis, a symptom that can alert physicians at an early stage of the disease. The purpose of this study was to investigate whether occult, visceral arterio-venous malformations could be detected by screening imaging studies in patients suffering from HHT. In a comprehensive diagnostic study, Rendu-Osler-Weber patients were examined for potential visceral arterio-venous malformations by physical examination and non-invasive imaging techniques. The Department of Otolaryngology of the Philipps University of Marburg is a major referral center and coordinated the screening procedures. Thirty-five individuals with the presumed diagnosis of HHT gave informed consent to the screening investigations. Eighteen of 35 individuals were found to suffer from visceral vascular malformations; most of the AVMs were diagnosed in the lung, but also the liver, spleen, brain and eyes were affected. Six patients could be treated preventively by arterial embolization for AVMs of the lung, liver and brain. Comprehensive screening for occult AVMs in HHT patients seems to be justified to avert potential complications in this group of patients.

Volumetric analysis of mice lungs in a clinical magnetic resonance imaging scanner.

Small animal models are widely used to study various pathologies. Magnetic resonance imaging (MRI) allows investigation of these animals in a non-invasive way. Therefore, the aim of our study was to develop and evaluate a low-cost approach to measure lung volumes in small animal MRI using a clinical scanner and a specially designed RF coil. Five mice (three of an established emphysema model and two controls) were investigated in a 1.0-T clinical scanner using a specially built small animal saddle coil and three different three-dimensional sequences; overall imaging time was approximately 16 min. Lung volumes were calculated from these images using an interactive watershed transform algorithm for semi-automatic image segmentation. The gold standard for the volume measurement was water displacement after surgical explantation. MRI measured volumes correlated significantly with ex vivo measurements on the explanted lungs (r = 0.99 to 0.89; p < 0.05). Mean lung volume in emphysema model mice was larger than in controls. High-resolution, small animal MRI using a clinical scanner is feasible for volumetric analysis and provides an alternative to a dedicated small animal scanner.

Effects of Nitinol Strecker Stent Placement on Vascular Response in Normal and Stenotic Porcine Iliac Arteries

PURPOSE This experimental study was conducted to evaluate neointimal thickness, lumen diameters, and histologic changes in normal and stenotic porcine iliac arteries following placement of self-expanding nitinol Strecker stents. MATERIALS AND METHODS Neointimal trauma causing slight vascular stenosis was induced unilaterally within external iliac arteries of 12 swines by means of endothelial abrasion and high cholesterol diet. Nitinol Strecker stents were placed within the stenotic and the normal contralateral vascular segments. For histopathologic evaluation, the pigs were killed 12 or 24 weeks after stent placement and luminal diamters were evaluated angiographically. RESULTS Excluding one occlusion, 15% narrowing of the lumen diameter was induced unilaterally (P = .002). Initial luminal gain after stent placement was greater for stenotic than for normal arteries. The amount of neointima thickness was not different between stenotic and normal vessels (P > .05). Comparing vascular diameters before stent placement and at follow-up, luminal loss due to neointima proliferation was 22% within normal arteries (P = .0002), while a luminal gain by 15% was found within the stenotic arteries (P = .008). Maturation of neointima and endothelial coverage were complete after 24 weeks. CONCLUSIONS Even though nitinol Strecker stents induce excessive neointimal proliferation, stenotic arteries seem to profit from great early luminal gain resulting in 15% of vascular expansion at follow-up while slight stenosis is induced within normal iliac arteries.

Treatment of Benign Tracheal Stenosis Utilizing Self-Expanding Nitinol Stents

We assessed the results of self-expanding metallic stent insertion into benign proximal tracheal stenosis in patients not appropriate or unfit for surgical repair. Proximal benign tracheal stenoses had occurred in 11 patients (7 men, 4 women, mean age 68.8 years) after long-time intubation (n = 6), tracheostomy (n = 4), or chondropathia (n = 1). Fourteen self-expanding nitinol stents were placed in the patients under general anesthesia with endoscopical and fluoroscopical guidance. Stent insertion was successful in all cases and led to immediate relief of the morphological and functional airway obstruction. No immediate complications were noted. During the mean follow-up period of 67.5 weeks we observed one recurrent dyspnea 3 months after implantation and granuloma formation at the stent insertion site in another patient. Both complications were successfully treated with additional stent insertion in one case and laser resection of granulomas in the other. Self-expanding nitinol stents should be considered for the treatment of benign proximal tracheal obstruction in selected patients for whom surgical repair is contraindicated.

Teleteaching with CONRAD. From case collections to an interactive teaching system

SummaryRadiological teaching files on the Internet suffer from certain restrictions such as limited user interactivity. The Internet teaching project CONRAD (computer online network for radiological didactics) circumvents these restrictions by using a new database structure that also reflects the development of a diagnosis over time. The cases are presented in the Internet with different HTML-based teaching programs. To support interactivity, CONRAD offers the building of online learning groups over the Internet.ZusammenfassungVorhandene radiologische Lehrmaterialien im Internet unterliegen einer Reihe von Einschränkungen wie einer starren Benutzerführung. Das Internetlehrprojekt CONRAD (Computer Online Netz RAdiologische Didaktik) umgeht diese Einschränkungen durch eine neue Datenbankstruktur, die auch den zeitlichen Verlauf der Diagnosestellung abbildet. Die verknüften Informationen der Datenbank werden mit unterschiedlichen HTML-basierten Lehrprogrammen im Internet präsentiert. Benutzer können über das Internet Lerngruppen bilden und gemeinsam an Fällen arbeiten.