http://repub.eur.nl/res/aut/7431/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/13410/ 2004-12-01T00:00:00Z BACKGROUND: Isolated hepatic perfusion for irresectable metastases confined to the liver has reported response rates of 50% to 75%. Magnitude, costs, and nonrepeatability of the procedure are its major drawbacks. We developed a less invasive, less costly, and potentially repeatable balloon catheter-mediated isolated hypoxic hepatic perfusion (IHHP) technique. METHODS: In this phase I and II study, 18 consecutive patients with irresectable colorectal or ocular melanoma hepatic metastases were included. Two different perfusion methods were used, both with inflow via the hepatic artery, using melphalan 1 mg/kg. In the first eight patients, the portal vein was occluded, and outflow was via the hepatic veins into an intracaval double-balloon catheter. This orthograde IHHP had on average 56% leakage. In next 10 patients, we performed a retrograde outflow IHHP with a triple balloon blocking outflow into the caval vein and allowing outflow via the portal vein. The retrograde IHHP still had 35% leakage on average. RESULTS: Although local drug concentrations were high with retrograde IHHP, systemic toxicity was still moderate to severe. Partial responses were seen in 12% and stable disease in 81% of patients. The median time to local progression was 4.8 months. CONCLUSIONS: We have abandoned occlusion balloon methodology for IHHP because it failed to obtain leakage control. We are presently conducting a study using a simplified surgical retrograde IHHP method, in which leakage is fully controlled, which translates into high response rates. http://repub.eur.nl/res/pub/10239/ 2003-01-01T00:00:00Z STUDY OBJECTIVES: Relapse-free survival in patients with sulcus superior tumors. DESIGN: Prospective registration study. SETTING: Department of surgical oncology of a university hospital. PATIENTS: Twenty-one patients treated with preoperative radiotherapy (46 Gy), lobectomy and chest-wall resection, and intraoperative radiotherapy (10 Gy). RESULTS: After a median follow-up of 18 months, 18 patients (85%) were free from locoregional relapse, while 8 patients were still alive. CONCLUSIONS: The results show that this protocol can achieve excellent local tumor control and can even be used for palliative treatment. http://repub.eur.nl/res/pub/8981/ 1998-01-01T00:00:00Z OBJECTIVE: To validate the methodology of isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques and to gain insight into the distribution of tumor necrosis factor-alpha (TNF), melphalan, and mitomycin C (MMC) through the regional and systemic blood compartments when applying these techniques. SUMMARY BACKGROUND DATA: There is no standard treatment for unresectable liver tumors. Clinical results of isolated limb perfusion with high-dose TNF and melphalan for the treatment of melanoma and sarcoma have been promising, and attempts have been made to extrapolate this success to the isolated liver perfusion setting. The magnitude and toxicity of the surgical procedure, however, have limited clinical applicability. METHODS: Pigs underwent IHHP with TNF, melphalan, and MMC using balloon catheters or served as controls, receiving equivalent dosages of these agents intravenously. After a 20-minute perfusion, a washout procedure was performed for 10 minutes, after which isolation was terminated. Throughout the procedure and afterward, blood samples were obtained from the hepatic and systemic blood compartments and concentrations of perfused agents were determined. RESULTS: During perfusion, locoregional plasma drug concentrations were 20- to 40-fold higher than systemic concentrations. Compared with systemic concentrations after intravenous administration, regional concentrations during IHHP were up to 10-fold higher. Regional MMC and melphalan levels steadily declined during perfusion, indicating rapid uptake by the liver tissue; minimal systemic concentrations indicated virtually no leakage to the systemic blood compartment. During isolation, concentrations of TNF in the perfusate declined only slightly, indicating limited uptake by the liver tissue; no leakage of TNF to the systemic circulation was observed. After termination of isolation, systemic TNF levels showed only a minor transient elevation, indicating that the washout procedure at the end of the perfusions was fully effective. CONCLUSIONS: Complete isolation of the hepatic vascular bed can be accomplished when performing IHHP using this balloon catheter technique. Thus, as in extremities, an ideal leakage-free perfusion of the liver can now be performed, and repeated, without major surgery. The effective washout allows the addition of TNF in this setting.