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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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The retrograde perfusion setup.
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Fig1: The retrograde perfusion setup.

Mentions: A right subcostal incision was performed, and the liver was mobilized from its retroperitoneal and diaphragmatic attachments. A prophylactic cholecystectomy was not performed routinely. Tributaries to the vena cava such as the adrenal, lumbar, and diaphragmatic veins were dissected and ligated. The vena cava was isolated and clamped above and below the liver, respectively, to prevent venous leakage. The portal vein, proper hepatic artery, and gastroduodenal artery were dissected, and the hepatic artery cannulated via the gastroduodenal artery with an 8 F catheter for inflow of the perfusate. In two patients, an aberrant left hepatic artery, coming from the left gastric artery was cannulated together with the proper hepatic artery for inflow. The portal vein was cannulated with a 14 F catheter for outflow. Patients subsequently received 2 mg/kg heparin. The hepatic artery catheter and the portal vein catheter were connected to the perfusion circuit primed with 220 mL Haemaccel (Behring Pharma, Amsterdam, The Netherlands). After clamping of the caval vein superior and inferior of the liver, clamping of the aorta just beneath the diaphragm, clamping the portal vein just above the pancreas, clamping the proper hepatic artery just proximal of the gastroduodenal branch, and clamping of the common bile duct with its surrounding tissue, the retrograde isolated perfusion was performed. The retrograde perfusion setup is depicted in Fig. 1.FIG. 1.


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)

The retrograde perfusion setup.
© Copyright Policy
Related In: Results  -  Collection

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

Fig1: The retrograde perfusion setup.
Mentions: A right subcostal incision was performed, and the liver was mobilized from its retroperitoneal and diaphragmatic attachments. A prophylactic cholecystectomy was not performed routinely. Tributaries to the vena cava such as the adrenal, lumbar, and diaphragmatic veins were dissected and ligated. The vena cava was isolated and clamped above and below the liver, respectively, to prevent venous leakage. The portal vein, proper hepatic artery, and gastroduodenal artery were dissected, and the hepatic artery cannulated via the gastroduodenal artery with an 8 F catheter for inflow of the perfusate. In two patients, an aberrant left hepatic artery, coming from the left gastric artery was cannulated together with the proper hepatic artery for inflow. The portal vein was cannulated with a 14 F catheter for outflow. Patients subsequently received 2 mg/kg heparin. The hepatic artery catheter and the portal vein catheter were connected to the perfusion circuit primed with 220 mL Haemaccel (Behring Pharma, Amsterdam, The Netherlands). After clamping of the caval vein superior and inferior of the liver, clamping of the aorta just beneath the diaphragm, clamping the portal vein just above the pancreas, clamping the proper hepatic artery just proximal of the gastroduodenal branch, and clamping of the common bile duct with its surrounding tissue, the retrograde isolated perfusion was performed. The retrograde perfusion setup is depicted in Fig. 1.FIG. 1.

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