Limits...
Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion.

Verhoef C, de Wilt JH, Brunstein F, Marinelli AW, van Etten B, Vermaas M, Guetens G, de Boeck G, de Bruijn EA, Eggermont AM - Ann. Surg. Oncol. (2008)

Bottom Line: Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs.IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP.The median duration of 9 months of tumor control should be improved.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology, Erasmus University Medical Centre-Daniel den Hoed Cancer Centre, PO Box 5201, 3008 AE, Rotterdam, The Netherlands. c.verhoef@erasmusmc.nl

ABSTRACT

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine.

Patients and methods: Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1-2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined.

Results: Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2-24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations.

Conclusions: IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.

Show MeSH

Related in: MedlinePlus

Drug-concentration versus time curve.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2277449&req=5

Fig2: Drug-concentration versus time curve.

Mentions: Figure 2 shows a drug concentration vs time curve in the isolated circuit in a patient with a pump infusion. The area under the concentration versus time curve (AUC) calculation showed a regional concentration of 2382 (μg × min/mL) versus undetectable systemic that makes the ratio AUC regional/systemic infinite (Fig. II). The median peak regional melphalan concentration was 68.04 μg/mL (range, 42.3–256.99) and negligibly low to undetectable systemic concentrations. After washout and subsequent releasing of the clamps, median peak systemic 4.2 μg/mL (range, 3.00–18.33) melphalan concentrations were observed. The AUC calculation showed a systemic concentration of 275 μg × min/mL after washout. Thus, intrahepatic melphalan concentrations during the IHHP are >9 fold higher than the post-IHHP systemic melphalan concentrations.FIG. 2.


Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion.

Verhoef C, de Wilt JH, Brunstein F, Marinelli AW, van Etten B, Vermaas M, Guetens G, de Boeck G, de Bruijn EA, Eggermont AM - Ann. Surg. Oncol. (2008)

Drug-concentration versus time curve.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2277449&req=5

Fig2: Drug-concentration versus time curve.
Mentions: Figure 2 shows a drug concentration vs time curve in the isolated circuit in a patient with a pump infusion. The area under the concentration versus time curve (AUC) calculation showed a regional concentration of 2382 (μg × min/mL) versus undetectable systemic that makes the ratio AUC regional/systemic infinite (Fig. II). The median peak regional melphalan concentration was 68.04 μg/mL (range, 42.3–256.99) and negligibly low to undetectable systemic concentrations. After washout and subsequent releasing of the clamps, median peak systemic 4.2 μg/mL (range, 3.00–18.33) melphalan concentrations were observed. The AUC calculation showed a systemic concentration of 275 μg × min/mL after washout. Thus, intrahepatic melphalan concentrations during the IHHP are >9 fold higher than the post-IHHP systemic melphalan concentrations.FIG. 2.

Bottom Line: Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs.IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP.The median duration of 9 months of tumor control should be improved.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology, Erasmus University Medical Centre-Daniel den Hoed Cancer Centre, PO Box 5201, 3008 AE, Rotterdam, The Netherlands. c.verhoef@erasmusmc.nl

ABSTRACT

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine.

Patients and methods: Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1-2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined.

Results: Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2-24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations.

Conclusions: IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.

Show MeSH
Related in: MedlinePlus