Tumoricidal Effects and Patient Survival After Hyperthermic Liver Perfusion

Skibba, Joseph L.; Quebbeman, Edward J.

doi:10.1001/archsurg.1986.01400110056009

Cited by 42 publications

(2 citation statements)

References 19 publications

(1 reference statement)

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“…Regional therapy of the liver without systemic damage may be achieved by the isolated liver perfusion techniques. Some methods have been described for perfusing the isolated liver and may be effective for hepatic malignancy [20]. However, the conventional techniques were complicated and expensive because of the need for an extracorporeal circuit with oxygenator and human blood.…”

Section: Discussionmentioning

confidence: 99%

Simple method of hyperthermo‐chemo‐hypoxic isolated liver perfusion for hepatic metastases

et al. 1994

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As a regional therapy for hepatic malignancy, we developed a simple method of isolated liver perfusion (hyperthermo-chemo-hypoxic). In the present study, the influence of this method on the hepatic tissue and other organs was experimentally evaluated and applied it to seven patients. Experimentally, all dogs survived without hepatic insufficiency and systemic toxicity. Clinically, one patient died on postoperative day 14 of hepatic failure. The reason was that liver temperature reached 43 degrees C, which seemed to be the maximum limit for thermal toxic effect to the human liver. The other six patients well tolerated the perfusion with mild increases of serum aminotransferase and total bilirubin levels and decreases of hepaprastin levels. Serum aminotransferase and total bilirubin and hepaprastin levels returned to normal levels by postoperative day 14. There were no significant differences between the isolated liver perfusion group (n = 7) and hepatectomy-only group (n = 27). Six patients were disease-free during the observation period after the perfusion. This system is a simple, useful method for treating patients with metastatic cancer limited to the liver.

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Section: Discussionmentioning

confidence: 99%

Simple method of hyperthermo‐chemo‐hypoxic isolated liver perfusion for hepatic metastases

et al. 1994

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“…Ausman, the first to use IHP in humans, administered nitrogen mustard to five patients under normothermic conditions [19]. Subsequently, other investigators reported on the clinical application of IHP, generally with poor results in terms of tumor response and with high hepatic toxicity rates [20][21][22][23][24][25][26][27][28]. More recently, Alexander et al reported encouraging results following the use of IHP in patients with liver metastases from eye melanoma or colorectal cancer [29][30][31][32].…”

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confidence: 99%

True versus Mild Hyperthermia during Isolated Hepatic Perfusion: Effects on Melphalan Pharmacokinetics and Liver Function

et al. 2004

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Hyperthermic antiblastic isolated hepatic perfusion (IHP) with melphalan has been recently proposed as an alternative therapeutic option for patients with unresectable liver tumors. Although melphalan-heat antiblastic synergism is at a maximum at temperatures higher than 41 degrees C, IHP has so far been performed in humans at lower temperatures. In this experimental work, we compared IHP under mild versus true hyperthermic conditions in terms of drug pharmacokinetics and liver function. Ten pigs were submitted to IHP with melphalan 1.5 mg/kg at a mean temperature of 40 degrees C (group A, n = 5) or 42 degrees C (group B, n = 5). After a 60-minute perfusion, a 15-minute washout was performed. Perfusate-to-plasma leakage was monitored using scintigraphy. Throughout perfusion, samples from the systemic blood, perfusate, and liver parenchyma were obtained to measure melphalan concentrations. Liver function was assessed using standard blood tests and the indocyanine green-based test. No deaths related to the IHP procedure were recorded. All animals had transient liver function impairment, with all liver function test results returning to normal within the observation period. At histologic examination, liver damage was similar under both hyperthermic conditions. Melphalan levels in the perfusate were not significantly different in the two study groups (the mean perfusate/plasma area under the curve from 0 to 60 minutes ratios were 463 and 501, respectively). These results correlated well with those obtained using the scintigraphic method. Liver drug concentrations remained unchanged after true hyperthermia IHP. Under true hyperthermic conditions, neither an increase in liver parenchyma toxicity nor changes in melphalan pharmacokinetics were observed. These findings support the use of true hyperthermia in the clinical setting to exploit fully the antitumor synergism between melphalan and heat.

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Percutaneous Isolated Hepatic Perfusion for Chemotherapy

Savier

Azoulay²,

Huguet³

et al. 2003

Arch Surg

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Background: Increasing the drug concentration in tumors may produce massive tumoral response. By using a variety of hepatic vascular isolation techniques, high concentrations of chemotherapeutic drugs may be achieved in the hepatic vascular bed. Hypothesis: Complete percutaneous isolated hepatic perfusion (IHP) is feasible and safe. Design: Case series. Setting: The hepatobiliary unit of a university hospital. Patients: Ten patients with irresectable and chemoresistant hepatic tumors were eligible for study participation; 4 patients with hepatic metastases of breast cancer, gastric cancer, colorectal cancer, and cholangiocarcinoma were included. Intervention: Patients received 3 successive courses of chemotherapy by IHP. The first course was given at laparotomy, and the next 2 courses were given percutaneously. The interval between courses was 3 to 6 weeks. Each course involved IHP of the liver for 15 to 30 minutes, without oxygenation, with 1 to 3 boluses of melphalan (15 mg). Main Outcome Measures: Morbidity and mortality. Results: Ten IHPs were performed (4 at laparotomy and 6 percutaneously). Concentrations of melphalan in the extracorporeal circulation were 10 times higher than those in the systemic circulation. Percutaneous IHPs had more leakage than those at laparotomy. However, hepatotoxicity was minimized. One patient experienced hepatic artery thrombosis, and 3 had severe neutropenia. Minor complications included ascites and pleural effusion. No deaths were observed 2 months after the last IHP. One partial response was observed (hepatic metastases of breast cancer). Conclusion: Percutaneous IHP for intensive chemotherapy is less aggressive and less hepatotoxic than IHP at laparotomy and may be iterative.

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Tumoricidal Effects and Patient Survival After Hyperthermic Liver Perfusion

Cited by 42 publications

References 19 publications

Simple method of hyperthermo‐chemo‐hypoxic isolated liver perfusion for hepatic metastases

Simple method of hyperthermo‐chemo‐hypoxic isolated liver perfusion for hepatic metastases

True versus Mild Hyperthermia during Isolated Hepatic Perfusion: Effects on Melphalan Pharmacokinetics and Liver Function

Percutaneous Isolated Hepatic Perfusion for Chemotherapy

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