Hepatic Arterial Infusion Therapy Research Articles

A method for hepatic arterial perfusion studies in the rat

The current model for selective hepatic arterial infusion therapy was evaluated for its suitability for short-term pharmacokinetic experiments. This preparation consists of selective cannulation of the common hepatic artery via the gastroduodenal artery of the rat. Radioactive microspheres were injected to determine hepatic or extrahepatic sites of perfusion. Radioactive microsphere determination of hepatic arterial flow and cardiac output were also performed. Our data indicate that at high flow rates (2 ml/min), significant loss of drug would occur due to retrograde flow. Modification of the model to include temporary proximal hepatic artery occlusion ensures hepatic delivery of greater than 95% of drug. Furthermore, temporary hepatic artery occlusion does not alter cardiac output or hepatic artery occlusion does not alter cardiac output or hepatic arterial blood flow. Selective hepatic arterial infusion in rats with synchronous temporary hepatic artery occlusion is an adequate model for short-term pharmacokinetic studies.

Good tolerance to high-dose hepatic arterial infusion therapy.

A pilot study was designed to evaluate the efficacy of high-dose FUDR administered through the hepatic artery for the treatment of cancer involving the liver. Three dose schedules were used beginning with a dose of 0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 2 weeks (schedule A). Elevation of serum bilirubin was the sole indication to deescalate to schedule B (0.3 mg FUDR/kg/day for two weeks followed by saline infusion for 4 weeks). Tolerance to this schedule escalated the patient to schedule C (0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 4 weeks). Eighteen patients were treated, sixteen with metastatic colon cancer, one with metastatic leiomyosarcoma, and one with hepatoma. The patient with hepatoma developed progressive disease after one cycle of therapy. Of the 17 patients with metastatic cancer only 5 patients failed therapy yielding a 70% response rate. High-dose FUDR was well tolerated with only six patients requiring deescalation to schedule B. Elevation of alkaline phosphatase and glutamic oxaloacetic transaminase was universal. Two patients developed peptic ulceration. Sclerosing cholangitis was not observed. We conclude that high-dose FUDR administered through the hepatic artery is as safe as conventional dose infusion therapy but probably not more effective. The safety of high-dose FUDR infusion therapy suggests that sclerosing cholangitis is association with hepatic arterial infusion therapy is not related to the FUDR dose.

The practicality of chronic hepatic artery infusion therapy of primary and metastatic hepatic malignancies: ten-year results of 124 patients in a prospective protocol.

Ten-year results are presented of 124 patients with malignancy apparently limited to the distribution of the hepatic artery, treated to prospective protocol with continuous infusion of 5-FUdR through an hepatic artery catheter. Nearly all patients had moderate to massive hepatic replacement. Of 88 patients with colorectal carcinoma, 64 (73%) had clinically objective and subjective remission. Median survival for responders was 13 months; for the entire group, ten months. Of 13 patients with hepatoma, nine had clinically significant regression with a median survival of 11 months. Ten patients had carcinoma of the gall bladder or bile duct with seven obtaining clinically significant regression. Complications encountered are discussed and are similar to other series. Of the patients experiencing clinically significant remission, all but one reached the complete independence performance status, and 84% reached normal activity levels. Thus, for hepatic localized tumor, this therapy is worthwhile and practical.

Proceedings: Primary liver cancer. A review of the clinical features, blood groups, serum enzymes, therapy, and survival of 65 cases.

A review of 65 patients with primary liver cancer was made. Of these, 53 had hepatocarcinoma. Primary cancer of the liver was most frequently found in patients aged 50 to 80 years, and was observed in three times as many males as females. There was an increased incidence of hepatocarcinoma in Negroes, especially those with blood group B. The most common symptoms with primary liver cancer were upper abdominal pain, weakness, and weight loss, while the most commonly found signs were hepatomegaly or an abdominal mass. Jaundice and ascites were also commonly found. Serum alkaline phosphatase, SGOT, SGPT, and LDH were elevated in most of these patients. In patients with hepatocarcinoma, 66% had histologically confirmed liver cirrhosis at autopsy. Serial alphafetoprotein tests were performed on 19 patients with hepatoma, in 14 of whom (73.6%) AFP was detectable. No Australia antigen was detected in 12 patients with hepatoma. In this study, 9 out of 16 patients (56%) had subjective and objective tumor responses with continuous 5-FUdR hepatic artery infusion. None of 18 patients treated with systemic cytotoxic agents responded. The difference in response between hepatic artery infusion and systemic therapy is statistically significant (P < .0002). There was a statistically significant lengthening in survival of patients who responded to intra-hepatic artery infusion as compared to non-responders and patients who received systemic chemotherapy. In reviewing the autopsy findings on 30 patients with hepatocarcinoma and 9 with cholangiocarcinoma, there were differences in the incidence of metastases to the lungs or bones between these two types of primary liver cancer.

Chronic Hepatic Artery Infusion Therapy of Primary and Metastatic Hepatic Malignancies.

s1 May 1969Chronic Hepatic Artery Infusion Therapy of Primary and Metastatic Hepatic Malignancies.Melvin L. Reed, M.D., V. K. Vaitkevicius, M.D., F.A.C.P., Clarence B. Vaughn, M.D.Melvin L. Reed, M.D.Search for more papers by this author, V. K. Vaitkevicius, M.D., F.A.C.P.Search for more papers by this author, Clarence B. Vaughn, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1106_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSystemic 5-fluorouracil (5-FU) therapy of gastroitestinal tumors produces objective tumor remissions in 12 to 20% of patients. Drug toxicity prevents administration of sufficient amounts of 5-FU to induce higher regression rates. With tuomrs limited to the liver, systemic therapy can be avoided. The liver receives a double blood supply, approximately 90 to 95% from the portal vein and 5 to 10% from the hepatic artery. Primary or metastatic tumor in the liver receives approximately 5 to 10% from the portal vein and 90 to 95% from the hepatic artery. Infusion of cytotoxic drugs directly into the hepatic artery delivers all... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Melvin L. Reed, M.D.; V. K. Vaitkevicius, M.D., F.A.C.P.; Clarence B. Vaughn, M.D.Affiliations: Detroit, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1106-1106KeywordsAdverse reactionsArteriesBloodDrug administrationDrugsGastroenterology and hepatologyLiverMetastatic tumorsPortal veins ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...