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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.

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Intra-hepatic bile duct necrosis after IHHP
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Fig3: Intra-hepatic bile duct necrosis after IHHP

Mentions: In three patients, bile duct necrosis occurred (Fig. 3). One of these patients was asymptomatic, and bile duct necrosis was found on routine CT scan during follow-up. Two of the patients with bile duct necrosis developed fever. No other explanation could be found for the fever, besides the intrahepatic “bilomas,” and therefore one patient was treated with percutaneous drainage and endoscopic stent placement in ductus choledochus. The other patient with fever received antibiotics. Both patients recovered, and slight elevations of bilirubin persisted, without complaints. In the first eight patients melphalan was administered as a bolus into the isolated liver circuit. After four patients melphalan dose was increased to 1.5 mg/kg in two patients and to 2 mg/kg melphalan in another two patients. Three of these patients (37.5%) developed bile duct necrosis, which is why the other 16 patients were treated with 1 mg/kg melphalan using a 10-minute pump infusion into the circuit. Bile duct necrosis did not occur in these patients. Postoperative chemical cholecystitis was not demonstrated.FIG. 3.


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)

Intra-hepatic bile duct necrosis after IHHP
© Copyright Policy
Related In: Results  -  Collection

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

Fig3: Intra-hepatic bile duct necrosis after IHHP
Mentions: In three patients, bile duct necrosis occurred (Fig. 3). One of these patients was asymptomatic, and bile duct necrosis was found on routine CT scan during follow-up. Two of the patients with bile duct necrosis developed fever. No other explanation could be found for the fever, besides the intrahepatic “bilomas,” and therefore one patient was treated with percutaneous drainage and endoscopic stent placement in ductus choledochus. The other patient with fever received antibiotics. Both patients recovered, and slight elevations of bilirubin persisted, without complaints. In the first eight patients melphalan was administered as a bolus into the isolated liver circuit. After four patients melphalan dose was increased to 1.5 mg/kg in two patients and to 2 mg/kg melphalan in another two patients. Three of these patients (37.5%) developed bile duct necrosis, which is why the other 16 patients were treated with 1 mg/kg melphalan using a 10-minute pump infusion into the circuit. Bile duct necrosis did not occur in these patients. Postoperative chemical cholecystitis was not demonstrated.FIG. 3.

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