Christos Rountas

Autologous Infusion of Expanded Mobilized Adult Bone Marrow-Derived CD34+ Cells Into Patients With Alcoholic Liver Cirrhosis

OBJECTIVES: Recent advances in regenerative medicine, including hematopoietic stem cell (HSC) transplantation, have brought hope for patients with severe alcoholic liver cirrhosis (ALC). The aim of this study was to assess the safety and efficacy of administering autologous expanded mobilized adult progenitor CD34+ cells into the hepatic artery of ALC patients and the potential improvement in the liver function.METHODS: Nine patients with biopsy-proven ALC, who had abstained from alcohol for at least 6 months, were recruited into the study. Following granulocyte colony-stimulating factor (G-CSF) mobilization and leukapheresis, the autologous CD34+ cells were expanded in vitro and injected into the hepatic artery. All patients were monitored for side effects, toxicities, and changes in the clinical, hematological, and biochemical parameters.RESULTS: On average, a five-fold expansion in cell number was achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 × 108 pre infusion. All patients tolerated the procedure well, and there were no treatment-related side effects or toxicities observed. There were significant decreases in serum bilirubin (P < 0.05) 4, 8, and 12 wk post infusion. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement through the study period and were significant (P < 0.05) 1 wk post infusion. The Child-Pugh score improved in 7 out of 9 patients, while 5 patients had improvement in ascites on imaging.CONCLUSION: It is safe to mobilize, expand, and reinfuse autologous CD34+ cells in patients with ALC. The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials.

Imaging Modalities for Renal Artery Stenosis in Suspected Renovascular Hypertension: Prospective Intraindividual Comparison of Color Doppler US, CT Angiography, GD-Enhanced MR Angiography, and Digital Substraction Angiography

The aim of the study was to evaluate the diagnostic accuracy of Color Doppler US, CT Angiography (CTA), and GD-enhanced MR Angiography (MRA) compared with digital subtraction angiography (DSA) for the detection of renal artery stenosis in patients with clinically suspected renovascular hypertension. Fifty-eight patients with suspected renovascular hypertension were enrolled in the study. All patients underwent Color Doppler US, CTA and GD-enhanced MRA. DSA was the gold standard method for the number of renal arteries, existence and degree of stenosis, or evidence of fibromuscular dysplasia. DSA depicted 132 renal arteries, 16 stenoses, and 4 arteries with fibromuscular dysplasia. Color Doppler US failed to detect 1 main and 14 polar arteries. CTA depicted all main renal arteries and 7/16 polar arteries, but failed to detect stenosis in two accessory vessels. Likewise, MRA did not detect stenotic accessory renal arteries, depicted 9/16 polar renal arteries, but missed two main renal arteries. All methods depicted the four main renal arteries with fibromuscular dysplasia. The overall sensitivity, specificity, and positive and negative predictive accuracy were 75%, 89.6%, 60% and 94.6%, respectively, for color Doppler US; 94%, 93%, 71%, and 99%, respectively, for CTA; and 90%, 94.1%, 75%, and 98%, respectively, for GD-enhanced MRA. CTA and GD-enhanced MRA have comparable and satisfactory results with respect to the negative predictive accuracy of the suspected renal artery stenosis. The concept of an imaging algorithm including US as screening test when appropriate and CTA or MRA as the second step-procedure is suggested. Therefore, DSA may be reserved for cases with major discrepancies or therapeutic interventions.

Minimally invasive and selective hydrodynamic gene therapy of liver segments in the pig and human

This paper highlights our experience of the transfer of hydrodynamic gene therapy (HGT) from the large animal, the pig, into clinical practice. The modification of balloon catheters and the development of a minimally invasive technique to allow selective isolation of liver segments for HGT in the large animal and human are described. Finally, our preliminary results from a phase I clinical study of HGT for thrombopoietin (TPO) in cirrhotic patients with thrombocytopenia are discussed. Based on these provisional data, minimally invasive selective HGT of liver segments appears to be technically safe, but further work is required to optimize the efficiency of gene transfer in order to achieve clinical benefit.

Influence of the Learning Curve on Safety and Efficiency of Laparoscopic Sleeve Gastrectomy

BackgroundLaparoscopic sleeve gastrectomy (LSG) is a relatively new bariatric procedure, and data regarding the learning curve are scarce. The aim of this study is to assess how the procedure can be safely implanted in a newly established bariatric unit and to define the learning curve.MethodsProctorship and mentorship in bariatric surgery were attended by two surgeons who were previously experienced in advanced laparoscopic surgery. The first consecutive 102 patients who underwent LSG in our newly established bariatric center were included. Patients were divided into three groups of 34 (groups 1, 2, and 3) according to case sequence. Data on demographics, operative time, conversion rate, hospital stay, morbidity, mortality, and excess weight loss (EWL) over time were compared between the groups.ResultsThe operative time was significantly lower in groups 2 (p = 0.016) and 3 (p = 0.003) compared to group 1. The learning curve was flat up to the 68th case. A significant decrease in hospital stay was noted for group 3 compared to groups 1 (p < 0.001) and 2 (p = 0.002). The conversion rate, mortality and morbidity rates, and EWL did not differ significantly between the groups. Mortality was 0.98% and procedure-related morbidity was 7.8%.ConclusionsLSG can be safely and efficiently performed in a newly established bariatric center following a mentorship procedure. Proficiency seems to require 68 cases. The operative time and hospital stay may significantly decrease with experience early in the learning curve, as opposed to mortality and morbidity rates, conversion rate, and EWL.

The Role of 3 Tesla MRA in the Detection of Intracranial Aneurysms.

Intracranial aneurysms constitute a common pathological entity, affecting approximately 1–8% of the general population. Their early detection is essential for their prompt treatment. Digital subtraction angiography is considered the imaging method of choice. However, other noninvasive methodologies such as CTA and MRA have been employed in the investigation of patients with suspected aneurysms. MRA is a noninvasive angiographic modality requiring no radiation exposure. However, its sensitivity and diagnostic accuracy were initially inadequate. Several MRA techniques have been developed for overcoming all these drawbacks and for improving its sensitivity. 3D TOF MRA and contrast-enhanced MRA are the most commonly employed techniques. The introduction of 3 T magnetic field further increased MRAs sensitivity, allowing detection of aneurysms smaller than 3 mm. The development of newer MRA techniques may provide valuable information regarding the flow characteristics of an aneurysm. Meticulous knowledge of MRAs limitations and pitfalls is of paramount importance for avoiding any erroneous interpretation of its findings.

A Novel Experimental Animal Model of Arterial Stenosis Based on Endovascular Radiofrequency Energy Application

ABSTRACT Purpose: To develop a new rabbit model of arterial stenosis using endovascular radiofrequency (RF) energy. Materials and Methods: Ten rabbits were used for multiple endovascular RF applications to the aorta and left common carotid artery through the Habib™ VesCoag™ catheter. Angiography and color Doppler ultrasound were used to assess vessel patency immediately following the procedure and six weeks later. One rabbit was sacrificed following the procedure for histopathologic analysis of the vessel wall. Two rabbits died of aortic and carotid rupture, respectively, immediately after the procedure. The remaining seven rabbits were sacrificed after six-week follow-up for histopathological analysis. Results: Optimal RF generator settings to induce significant arterial stenosis (>50%) without complications were standardized at 24–26 watts (W) for 1.5 min for the aorta and 6 W for 1 min for the common carotid artery. The six-week follow-up showed permanent results in all surviving rabbits. Histopathology revealed intima and medial smooth muscle layer necrosis. Conclusion: We have developed a novel rabbit model of arterial stenosis using endovascular RF energy. Our model is fast, safe, inexpensive, and reproducible. It would be useful for experimental investigations and new therapeutic devices.

Safety and Efficacy of Transcatheter Arterial Chemoemboliazation in the Real-Life Management of Unresectable Hepatocellular Carcinoma

Background Trans-arterial chemoembolization (TACE) is associated with better survival in BCLC-stage B patients with hepatocellular carcinoma (HCC) and Child-Pugh A whereas in Child-Pugh B there is no definite evidence of benefit. Objectives To assess the safety and efficacy of TACE during routine clinical practice in a consecutive Greek cohort of patients with unrespectable HCC. Patients and Methods Seventy one patients enrolled for this study (mean follow-up:24.6 months). 100 mg cisplatin, 50 mg doxorubicin and 10 ml lipiodol as well as embolic materials were used. CT-scans and blood tests were obtained prior and post-TACE. Kaplan–Meier method and Cox proportional hazard model were used to evaluate survival and factors affecting survival. Results Survival at 1-year, 2-years, 3-years and 5-years was 73.2%, 45.4%, 33.2% and 14.9% respectively. Procedure-related mortality was 1.4%. Multivariate analysis showed lesion diameter, Child-Pugh classification, alcohol abuse, tumor response and AFP prior TACE as independent prognostic factors of survival. Patients diagnosed during surveillance had significantly better survival rates compared to those diagnosed after development of symptoms (HR = 0.58, 95%CI: 0.33-1.01, P < 0.05). Conclusions TACE is safe and efficient for unrespectable HCC. Alcohol abuse, tumor burden, response criteria, Child-Pugh and AFP prior to the session were identified as independent predictors of survival whereas, adherence to surveillance programs resulted in significantly better survival in these patients.

Initial data on a novel endovascular radiofrequency catheter when used for arterial occlusion in liver cancer

ZusammenfassungGRUNDLAGEN: Wir untersuchten die Sicherheit und Wirksamkeit eines neuen endovaskulären Radiofrequenzkatheters (VesCoag) für den Arterienverschluss beim Management von Lebertumoren. METHODIK: Die Patienten hatten einen nicht resektablen primären oder sekundären Lebertumor. Der primäre Endpunkt war, ob VesCoag in das Zielgefäß eingebracht werden konnte, der sekundäre Endpunkt, ob es zu einem Angiographie-geprüften Verschluss des Gefäßes kam. ERGEBNISSE: VesCoag wurde bei 13 Patienten angewendet (4 Metastasen, 7 hepatozelluläre Karzinome, 2 intrahepatale Gallenganskarzinome). In allen Fällen konnte VesCoag ohne Komplikation (Ruptur, Dissektion) in die Zielgefäße eingebracht werden. Die Durchleuchtungszeit betrug 12,86 min, die Sondenaktivierung 240 (20–600) sec. Die abgegebene Energie betrug 2 W–120 W. Die bipolare Radiofrequenz konnte in keinem Fall einen adäquaten Gefäßverschluss erzielen, deshalb wurde der monopolare Modus verwendet. 4mal kam es zu Schmerzen, ein angiographisch nachgewiesener Verschluss wurde in 11 Fällen erzielt. 12 der 13 Patienten erhielten eine weiterführende Therapie (10× Chemoembolization, 1× Chemotherapie, 1× Lipiodol). SCHLUSSFOLGERUNGEN: Diese erste Erfahrung mit VesCoag zeigt, dass die Methode sicher ist und einen gezielten Verschluss von Zielgefäßen erlaubt.SummaryBACKGROUND: To assess the safety and effectiveness of a newly designed endovascular radiofrequency (RF) catheter (VesCoag) when used for arterial occlusion in the management of liver cancer. METHODS: Patients considered for the study had either primary or secondary cancer of the liver, which was not suitable for initial surgical resection. The primary endpoint of the study was whether VesCoag could be manipulated into the target blood vessel and the secondary endpoint was whether on angiography the blood vessel had been sealed. RESULTS: VesCoag was used in 13 patients. The indications for treatment were metastatic disease in 4, hepatocellular carcinoma in 7, and intrahepatic cholangiocarcinoma in 2. In all cases, VesCoag was manipulated into the target vessel for activation. There were no technical problems such as vessel dissection or rupture. The average fluoroscopic time was 12.86 min and the mean duration of probe activation was 240 (range 20–600) seconds. The lowest wattage used was 2 W and the highest 120 W. In no cases was bipolar radiofrequency activation sufficient to produce vessel sealing, so monopolar mode was used throughout. There were four minor complications of pain. The angiographic endpoint of target vessel occlusion was achieved in 11 patients. In 12 out of 13 cases an additional endovascular therapeutic maneuver was performed after VesCoag activation. These additional therapies were chemoembolization n = 10, chemotherapy n = 1, and lipiodol n = 1. CONCLUSIONS: This early assessment of VesCoag shows it to be safe and fulfill its design remit of being able to produce precise occlusion of the targeted vessel.

Tryptophan depletion under conditions that imitate insulin resistance enhances fatty acid oxidation and induces endothelial dysfunction through reactive oxygen species-dependent and independent pathways

In the original publication of the article, last author’s name was misspelt. The correct name is given here.

Experimental animal study of a novel radiofrequency endovascular occlusion device

BACKGROUND The purpose of this study was to present a radiofrequency (RF) endovascular occlusion device (ie, Habib VesCoag Catheter; EMcision Ltd, London, UK) and to evaluate safety and efficacy of the device for complete occlusion of normal porcine vessels. METHODS The study included 20 pigs. In each pig, a segmental branch of the right hepatic artery, a branch of the splenic artery, and a branch of one of the renal arteries were catheterized. A single or multiple applications of RF energy were performed until vessel occlusion was achieved. Fifteen days later, angiography was repeated to assess vessel patency. The vessels were then excised for pathological analysis. RESULTS Vessels 2.5 to 6 mm in diameter were treated. Complete occlusion with a single attempt was achieved using a mean amount of energy of 110.67 J in vessels 2.5 to 3 mm, 111.67 J in vessels 3.5 to 4 mm, and 116.63 J in vessels 5 to 6 mm in diameter and was confirmed by angiography at the 15-day follow-up. CONCLUSIONS Vascular occlusion can be effectively and safely achieved by endovascular application of RF energy to normal porcine arteries using the Habib VesCoag catheter.