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Michael Galanski

Publications and source records attributed to Michael Galanski.

At least 19 recordsLinked to original sources
PubMed2006

Insertion of virtual pulmonary nodules in CT data of the chest: development of a software tool.

The purpose of this study was to develop a software tool for the insertion of virtual lung nodules into CT data. Forty software-generated nodules were inserted at random locations and sizes on 20 multi-detector row CT studies of the chest (4 x 1-2.5-mm slice collimation). On each scan, two virtual nodules were inserted. The size, shape, margin and attenuation could arbitrarily vary and were individually adjusted to match real lesions of each patient (real nodules: 6.5+/-3.1 mm; virtual nodules: 6.1+/-3.2 mm). Additionally, noise and a random pattern simulating local density variations were added to virtual nodules. Three blinded readers evaluated 40 real and 40 simulated nodules according to a 5-point confidence scale ranging from 1 (definitely simulated) to 5 (definitely real). A multivariate analysis of covariance was performed for statistical assessment (SPSS 11.5, Chicago, IL). Real and simulated lesions were indistinguishable for all three readers (Pillai's trace statistic: P=0.881). However, nodule size was a statistically significant covariable regarding the differentiation of virtual compared to real nodules. Larger simulated nodules were easier to detect than smaller ones (Pillai's trace statistic: P<0.05). The developed algorithm allowed for the synthetic generation of lung nodules that were indistinguishable from real nodules.

Algorithms↗
PubMed2006

Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma.

AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, alpha-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses. RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%, and 43%) compared to PEI treatment alone (2) (1-, 3-, 5-year survival: 65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%) while PEI after stratification to best supportive care (4) was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n < 5), tumor size (< 5 cm), no ascites before PEI, and stable serum cholinesterase after PEI (P < 0.05). The mortality within 2 wk after PEI was 2.8% (n = 3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All complications could be managed non-surgically. CONCLUSION: Repeated single-session PEI is effective in patients with advanced HCC at an acceptable and manageable complication rate. Patients stratified to a combination of TACE and PEI can expect longer survival than those stratified to repeated PEI alone. Furthermore, patients with large or multiple tumors in good clinical status may also profit from a combination of TACE and reconsideration for secondary PEI.

Adult↗
PubMed2006

Preoperative volume calculation of the hepatic venous draining areas with multi-detector row CT in adult living donor liver transplantation: Impact on surgical procedure.

OBJECTIVE: The purpose was to assess the volumes of the different hepatic territories and especially the drainage of the right paramedian sector in adult living donor liver transplantation (ALDLT). METHODS: CT was performed in 40 potential donors of whom 28 underwent partial living donation. Data sets of all potential donors were postprocessed using dedicated software for segmentation, volumetric analysis and visualization of liver territories. During an initial period, volumes and shapes of liver parts were calculated based on the individual portal venous perfusion areas. After partial hepatic congestion occurring in three grafts, drainage territories with special regard to MHV tributaries from the right paramedian sector, and the IRHV were calculated additionally. Results were visualized three-dimensionally and compared to the intraoperative findings. RESULTS: Calculated graft volumes based on hepatic venous drainage and graft weights correlated significantly (r = 0.86, P < 0.001). Mean virtual graft volume was 930 ml and drained as follows: RHV: 680 ml, IRHV: 170 ml (n = 11); segment 5 MHV tributaries: 100 ml (n = 16); segment 8 MHV tributaries: 110 ml (n = 20). When present, the mean aberrant venous drainage fraction of the right liver lobe was 28%. CONCLUSION: The evaluated protocol allowed a reliable calculation of the hepatic venous draining areas and led to a change in the hepatic venous reconstruction strategy at our institution.

Adult↗
PubMed2005

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver.

AIM: In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver. METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m(2)) and additional transarterial chemoembolization procedures (50 mg/m(2) cisplatin, 50 mg/m(2) doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity. RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO III/IV) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo. CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.

Aged↗
PubMed2005

In vitro validation of phase-contrast flow measurements at 3 T in comparison to 1.5 T: precision, accuracy, and signal-to-noise ratios.

PURPOSE: To evaluate the signal-to-noise ratio (SNR), precision, and accuracy of phase-contrast flow measurements at 3 T with the help of an in vitro model and to compare the results with data from two 1.5-T scanners. MATERIALS AND METHODS: Using an identical setup of a laminar flow model and sequence parameters, measurements were done at one 3-T and at two 1.5-T systems. Precision, accuracy, and SNR were obtained for velocity encodings ranging from 55 up to 550 cm(-1). SNRs were calculated from the magnitude as well as the flow encoded images. RESULTS: Precision and accuracy for the in vitro flow model were similarly high in all scanners with no significant difference. For velocity encodings from 55 cm(-1) up to 550 cm(-1), the SNR in magnitude as well as phase encoded images of the 3-T measurements was approximately 2.5 times higher than the SNR obtained from the two 1.5-T systems. CONCLUSION: Even without optimization for the 3-T environment, flow measurements show the same high accuracy and precision as is known from clinical 1.5-T scanners. The superior SNR at 3 T will allow further improvements in temporal and spatial resolution. This will be of interest for small-size vessels like coronary arteries or for slow diastolic flow patterns.

Blood Flow Velocity↗
PubMed2005

Hybrid endograft for one-step treatment of multisegment disease of the thoracic aorta.

PURPOSE: At present, a two-step surgical approach is necessary to treat patients with coexistent pathologic conditions involving the proximal and descending thoracic aorta. A hybrid endograft is described here that enables such treatment during a single operation. MATERIALS AND METHODS: The Chavan-Haverich endograft consists of a Dacron vascular prosthesis with stainless-steel stents affixed at its distal end. After approval by the institutional review board, the endograft was prospectively implanted in 22 patients with multisegment thoracic aortic disease (13 men, nine women; median age, 64 years). Eleven patients had type A dissections (one acute, 10 chronic), four had a chronic type B dissection, and seven had atherosclerotic aneurysms of the ascending aorta or aortic arch as well as of the descending aorta. Of these patients, 11 additionally required aortic valve replacement or coronary artery bypass grafting. Via median sternotomy, the aortic arch was opened in circulatory arrest. After antegrade deployment of the stent-containing portion in the descending aorta, the proximal non-stent-containing endograft was used to reconstruct the aortic arch. Median follow-up was 14 months. RESULTS: Endograft implantation was successful in all but one patient. Complications included neurologic deficits that were transient in one case and lasting in two, two cases of vocal cord paralysis, and one death. In all patients with atherosclerotic aneurysms who received the endograft (six of seven), aneurysm thrombosis was noted at follow-up. In aortic dissections, partial or complete false-lumen thrombosis to the level of the stents occurred in all patients. None of the patients showed a progressive widening of the descending aorta. CONCLUSION: The Chavan-Haverich endograft enables one-step treatment of multisegment pathologic conditions affecting the thoracic aorta that otherwise would require two or more operations.

Aged↗
PubMed2004

Transcutaneous perianal sonography: a sensitive method for the detection of perianal inflammatory lesions in Crohn's disease.

AIM: Pelvic magnetic resonance imaging (MRI) and endoanal ultrasound which are established imaging methods for perianal inflammatory lesions in patients with Crohn's disease require expensive specialized equipments and expertise. We investigated the feasibility and sensitivity of transcutaneous perianal ultrasound (PAUS) using regular ultrasound probes in the imaging of perianal inflammatory lesions. The sonographic findings were correlated to pelvic MRI-scans. METHODS: We performed PAUS in 25 patients with Crohn's disease and clinical signs of perianal inflammatory disease. Within a median of 10 d (range 0-75) these patients underwent MRI of the pelvis. Regular convex and linear high resolution probes were used for PAUS. The sonographic findings were correlated to the MRI findings by blinded investigators. RESULTS: The sonographic investigations were well tolerated by all patients. Fistulae typically presented as hypoechoic tracks. Twenty-nine fistulae were detected in 22 patients. Abscesses were detected in 7 patients and presented as hypo- or anechoic formations. Twenty-six of 29 fistulae and 6 of 7 abscesses could be confirmed by MRI. Kappa statistics showed an excellent agreement (kappa>0.83) between the two imaging methods. CONCLUSION: PAUS is a simple, painless, feasible, real-time method that can be performed without specific patient preparation which is comparable in its sensitivity to pelvic MRI in the detection of perianal fistulae and/or abscesses. PAUS can especially be recommended as a screening tool in acute perianal disorders such as perianal abscess and for follow-up studies of perianal inflammatory disease.

Anal Canal↗
PubMed2004

Hepatic artery embolization for treatment of patients with hereditary hemorrhagic telangiectasia and symptomatic hepatic vascular malformations.

At present there is no established therapy for treating patients with hereditary hemorrhagic telangiectasia (HHT) and symptomatic hepatic involvement. We present the results of a prospective study with 15 consecutive patients who were treated with staged hepatic artery embolization (HAE). Branches of the hepatic artery were selectively catheterized and embolized in stages using polyvinyl alcohol particles (PVA) and platinum microcoils or steel macrocoils. Prophylactic antibiotics, analgesics and anti-emetics were administered after every embolization. Clinical symptomatology and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 28 months; range 10-136 months). Five patients had abdominal pain and four patients had symptoms of portal hypertension. The cardiac output was raised in all patients, with cardiac failure being present in 11 patients. After treatment, pain resolved in all five patients, and portal hypertension improved in two of the four patients. The mean cardiac output decreased significantly ( P<0.001) from 12.57+/-3.27 l/min pre-treatment to 8.36+/-2.60 l/min at the end of follow-up. Symptoms arising from cardiac failure resolved or improved markedly in all but one patient. Cholangitis and/or cholecystitis occurred in three patients of whom two required a cholecystectomy. One patient with pre-existent hepatic cirrhosis died as a complication of the procedure. Staged HAE yields long-term relief of clinical symptoms in patients with HHT and hepatic involvement. Patients with pre-existing hepatic cirrhosis may be poor candidates for HAE.

Adult↗
PubMed2004

New indications for computer-assisted surgery: tumor resection in the pelvis.

The resection of recurrent malignant pelvic tumors was supported by a commercially available navigation system in three patients. Preoperatively three-dimensional images from the pelvis were obtained by computed tomography or magnetic resonance imaging to identify the tumor extension. During surgery navigated tools oriented the surgeon to excise the tumor with adequate virtual margins. Navigation was helpful for tumor identification in one patient with a recurrent presacral mesenchymal chondrosarcoma. In the other two patients the tumor resection in the bone was done with three-dimensional observation of the osteotomies in the sacrum. In all three patients the histopathologic analysis confirmed that the neoplasms were excised accurately within their margins. We think that computer-assisted surgery is a potential method to increase the accuracy of tumor resections.

Adult↗
PubMed2004

Assessment of sequential enhancement patterns of focal nodular hyperplasia and hepatocellular carcinoma on mangafodipir trisodium enhanced MR imaging.

RATIONALE AND OBJECTIVES: Sequential contrast changes of mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance imaging (MRI) were evaluated in the differentiation of focal nodular hyperplasias (FNH) and hepatocellular carcinomas (HCC). METHODS: Patients with FNH (n = 16) or HCC (n = 12) underwent MRI: T2-weighted fast spin echo before and T1-weighted gradient echo before and 1, 4, 14, and 22 hours after 5 micromol/kg Mn-DPDP. Homogeneity of enhancement and delineation of fibrous scars of FNHs were assessed qualitatively. Lesion-to-liver contrast changes of FNHs and HCCs were compared quantitatively (Mann-Whitney U). RESULTS: Mn-DPDP improved detection of characteristic scars of FNHs from 50% before to 90% after contrast agent. Apart from fibrous tissue enhancement of FNHs was mostly homogeneous (90%). Time-dependent contrast changes were up to 20 times higher (after 4 hours) for FNHs than HCCs (P < 0.0001). CONCLUSIONS: Mn-DPDP-enhanced MRI helps to delineate characteristic morphologic features of FNHs and can provide quantitative data differentiating FNH and HCC.

Adult↗
PubMed2003

3D CT modeling of hepatic vessel architecture and volume calculation in living donated liver transplantation.

The aim of this study was to evaluate a software tool for non-invasive preoperative volumetric assessment of potential donors in living donated liver transplantation (LDLT). Biphasic helical CT was performed in 56 potential donors. Data sets were post-processed using a non-commercial software tool for segmentation, volumetric analysis and visualisation of liver segments. Semi-automatic definition of liver margins allowed the segmentation of parenchyma. Hepatic vessels were delineated using a region-growing algorithm with automatically determined thresholds. Volumes and shapes of liver segments were calculated automatically based on individual portal-venous branches. Results were visualised three-dimensionally and statistically compared with conventional volumetry and the intraoperative findings in 27 transplanted cases. Image processing was easy to perform within 23 min. Of the 56 potential donors, 27 were excluded from LDLT because of inappropriate liver parenchyma or vascular architecture. Two recipients were not transplanted due to poor clinical conditions. In the 27 transplanted cases, preoperatively visualised vessels were confirmed, and only one undetected accessory hepatic vein was revealed. Calculated graft volumes were 1110 +/- 180 ml for right lobes, 820 ml for the left lobe and 270 +/- 30 ml for segments II+III. The calculated volumes and intraoperatively measured graft volumes correlated significantly. No significant differences between the presented automatic volumetry and the conventional volumetry were observed. A novel image processing technique was evaluated which allows a semi-automatic volume calculation and 3D visualisation of the different liver segments.

Adult↗
PubMed2003

Low-contrast detectability in volume rendering: a phantom study on multidetector-row spiral CT data.

To cope with the increasing amount of CT data, there is growing interest in direct volume-rendering techniques (VRT) as a diagnostic tool. The aim of this phantom study was to analyze the low-contrast detectability (LCD) of VRT compared with multi-planar reformations (MPR). Soft tissue lesions were simulated by spheres of different diameters (3-8 mm). The average lesion density was 15 HU compared with a background density of 35 HU. Two different CT protocols with 40 and 150 mAs were performed on a multi-detector row CT. The scanning parameters were as following: 140 kV; 2x0.5-mm slice collimation; pitch 2 (table movement per rotation/single slice collimation), and reconstruction with 0.5-mm slice thickness at 0.5-mm interval. A B30 kernel was used for reconstruction. The VRT was performed by mapping Hounsfield values to gray levels equal to a CT window (center: 60 HU; window: 370 HU ). A linear ramp was applied for the opacity transfer function varying the maximum opacity between 0.1 and 1.0. A statistical method based on the Rose model was used to calculate the detection threshold depending on lesion size and image noise. Additionally, clinical data of 2 patients with three liver lesions of different sizes and density were evaluated. In VRT, LCD was most dependent on object size. Regarding lesions larger than 5 mm, VRT is significantly superior to MPR (p<0.05) for all opacity settings. In lesions sized 3-5 mm a maximum opacity level approximately 40-50% showed a near equivalent detectability in VRT and MPR. For higher opacity levels VRT was superior to MPR. Only for 3-mm lesions MPR performed slightly better in low-contrast detectability (p<0.05). Compared with MPR, VRT shows similar performance in LCD. Due to noise suppression effects, it is suited for visualization of data with high noise content.

Aged↗
PubMed2003

Endoluminal treatment of aortic dissection.

Aortic dissection is most often a catastrophic medical emergency which, if untreated, can be potentially fatal. The intention of therapy in patients with aortic dissection is to prevent aortic rupture or aneurysm formation as well as to relieve branch vessel ischaemia. Patients with aortic dissection are often poor candidates for anaesthesia and surgery and the surgical procedure itself is challenging requiring thoracotomy, aortic cross clamping, blood transfusion as well as prolonged hospital stay in some cases. Operative mortality is especially high in patients with critical mesenteric or renal ischaemia. The past decade has experienced the emergence of a number of interventional radiological or minimally invasive techniques which have significantly improved the management of patients with aortic dissection. These include stent grafting for entry site closure to prevent aneurysmatic widening of the false lumen as well as percutaneous techniques such as balloon fenestration of the intimal flap and aortic true lumen stenting to alleviate branch vessel ischaemia. False lumen thrombosis following entry closure with stent grafts has been observed in 86-100% of patients, whereas percutaneous interventions are able to effectively relieve organ ischaemia in approximately 90% of the cases. In the years to come, it is to be expected that these endoluminal techniques will become the method of choice for treating most type-B dissections and will assist in significantly reducing the number of open surgical procedures required for type-A dissections. The intention of this article is to provide an overview of the current status of these endoluminal techniques based on our own experience as well as on a review of the relevant literature.

Aortic Dissection↗
PubMed2003

Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up.

Propionibacterium acnes (P. acnes) is suspected to be involved in the pathophysiology of SAPHO syndrome, since it has been isolated repeatedly through open surgical bone biopsy. This study demonstrates the role of MRI in identifying inflamed bone areas in patients with SAPHO syndrome and the role of CT-guided bone biopsies in obtaining samples from these areas for microbiological and histopathological investigations, thus obviating open surgery. Fourteen consecutive patients with SAPHO syndrome were investigated by MRI to identify acute inflammatory changes in hyperostotic periarticular bone. The CT-guided biopsies for microbiological investigations were taken from the areas identified. Patients positive for P. acnes were started on long-term antibiotic therapy according to antibiotic susceptibility. On MRI the inflammatory changes appeared as hyperintense areas on fat-saturated T2 fast-spin-echo (FSE) images and showed signal increase on fat-saturated T1 SE images after Gd-DTPA. With MR localization CT-guided bone biopsies yielded P. acnes in 8 patients. No bacteria could be isolated from the remaining 6 patients. Acute inflammatory bone changes in SAPHO syndrome are well localized by MRI. With MR localization, CT-guided bone biopsies offer a minimally invasive alternative to open surgery in the detection of. P. acnes leading to the institution of a specific antibiotic therapy.

Acquired Hyperostosis Syndrome↗
PubMed2003

Kissing balloon technique for angioplasty of renal artery bifurcation stenoses.

This study evaluates long-term results after using the kissing balloon technique in percutaneous transluminal angioplasty of bifurcation stenoses of the renal artery. Eight patients with proven renal artery stenosis and deterioration of renal function were treated, including one kidney transplant recipient. Follow-up ranged between 3 and 131 months. All interventions were technically successful. All patients improved in one or more of the following: serum creatinine levels and creatinine clearance, blood pressure, and need for antihypertensive medication. The kissing balloon technique is a reliable and safe method for treating bifurcation stenoses of the renal artery, rendering stable long-term results.

Adult↗
PubMed2002

Contrast media nephropathy: intravenous CT angiography versus intraarterial digital subtraction angiography in renal artery stenosis: a prospective randomized trial.

BACKGROUND: Spiral computed tomographic angiography (CTA) is a noninvasive method to diagnose renal artery stenosis (RAS). In digital subtraction angiography (DSA), contrast media (CM) is injected directly into the renal artery; in CTA, a greater amount of CM is injected intravenously, potentially leading to an increased incidence of CM nephropathy. METHODS: We investigated 80 patients with suspected RAS randomized to either CTA or DSA prospectively. The following parameters were determined: serum creatinine level and single-shot inulin clearance for evaluation of renal function and urine alpha1-microglobulin and beta-N-acetyl-glucoseaminidase (beta-NAG) as markers for tubular toxicity. Data from 16 patients undergoing angioplasty in the same session were excluded. RESULTS: In the CTA and DSA groups, 163 +/- 13 and 104 +/- 56 mL of CM (mean +/- SD; P < 0.0001) were administered, respectively. Mean serum creatinine levels increased from 1.78 +/- 1.61 to 1.92 +/-1.73 mg/dL (157 +/- 142 to 170 +/- 153 micromol/L; P = 0.00001) in the CTA group and from 1.52 +/- 1.23 to 1.60 +/- 1.28 mg/dL (134 +/- 109 to 141 +/- 113 micromol/L; P = 0.01) in the DSA group. Mean inulin clearance decreased from 63 +/- 28 to 58 +/- 23 mL/min (P = 0.01) and 65 +/- 26 to 62 +/- 26 mL/min (P < 0.01), median beta-NAG levels increased from 4.6 to 6.0 U/g creatinine (P = not significant) and 2.5 to 8.0 U/g creatinine (P < 0.001), and median alpha1-microglobulin levels increased from 13 to 17 microg/g creatinine (P < 0.025) and 11 to 21 microg/g creatinine (P = not significant) in the CTA and DSA groups, respectively. CM nephropathy occurred in 3 of 33 patients in the CTA group and 2 of 31 patients in the DSA group. The increase in creatinine level was reversible in all patients within 7 days. CONCLUSION: On this study, CTA performed for the detection of RAS is not associated with an increased risk for CM nephropathy compared with intraarterial DSA despite a greater dose of CM.

Angiography, Digital Subtraction↗
PubMed2002

Gene therapy by intrahepatic and intratumoral trafficking of p53-VP22 induces regression of liver tumors.

BACKGROUND & AIMS: VP22-mediated intercellular transport provides an approach to deliver functional chimeric proteins into a high percentage of target cells. The aim of this study was to evaluate the efficacy of p53/VP22 fusion protein in gene therapy of liver tumors. METHODS: Expression vectors of N- and C-terminal fusion proteins of p53 and VP22 were subcloned and transcriptional properties of chimeric proteins were assessed by luciferase assays. Adenoviral vectors expressing p53 wild type (AdGFP/p53wt) and p53-VP22 (AdGFP/p53-VP22) were generated to investigate the VP22-mediated spreading in normal liver and in liver tumors in vivo by green fluorescent protein fluorescence and p53 immunohistochemistry. Gene therapy was investigated in subcutaneous and preclinical orthotopic animal tumor models after subcutaneous and intra-arterial administration of the adenoviruses, and tumor growth was assessed by direct calibration and magnetic resonance imaging. RESULTS: p53-VP22 showed enhanced transcriptional activity compared with p53 wild type. VP22-mediated intercellular transport of p53 could be observed in the normal liver and in liver tumors in vivo and was correlated with increased antitumor efficacy of gene therapy and improved survival of the animals. CONCLUSIONS: Fusion of VP22 to p53 strongly improves the results of p53 replacement gene therapy. Furthermore, the demonstrated VP22-mediated intercellular transport in the liver could be important for other strategies in liver gene therapy, providing a tool for enhancing the effect of gene therapy in liver diseases such as metabolic disorders or viral hepatitis.

Adenoviridae↗