
Hepatic Arterial Infusion [HAI] & Liver Metastases

Hepatic Arterial Infusion [HAI] has been used for many years to treat liver tumors (primary or secondary) if no extrahepatic extension exists, when no resection is feasible, and when no active systemic chemotherapy is available. It is also useful for downgrading inoperable situations to operable ones. 

 [There is a slow pumping of chemotherapy agents into the hepatic artery.  LMS liver metastases get their blood supply from the hepatic artery.  So they get a higher concentration of the chemotherapy agent, than if it was given intravenously.  The liver can tolerate a higher concentration of the chemotherapy agent than the rest of the body, because it detoxifies it right then and there.  So the liver mets get a higher concentration of the chemotherapy agent, and the liver detoxifies the rest of the blood so that the rest of the body is shielded somewhat from the chemo agent.]

Infusion of cytotoxic agents into the hepatic artery is a form of therapy for unresectable hepatic metastases. The recent development of a totally implantable pump has allowed prolonged infusion of chemotherapeutic agents with good compliance and quality of life. The use of agents with high hepatic extraction results in minimal systemic toxicity. Such regional chemotherapy can increase the likelihood of hepatic response compared with systemic treatment. 

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<b>Hepatic Arterial Infusion [HAI] & Liver Metastases 
Selected Medical Journal Article Annotated Citations </b>
[For the full abstract, use the links provided, or search on Pubmed.  Ed.]


Oncol Res. 1999;11(11-12):529-37. 
<b>A clinical-pharmacological evaluation of percutaneous isolated hepatic infusion of doxorubicin in patients with unresectable liver tumors.</b>Hwu WJ, Salem RR, Pollak J, Rosenblatt M, D'Andrea E, Leffert JJ, Faraone S, Marsh JC, Pizzorno G.
Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. hwuw@mskcc.org

A dose escalation study of hepatic arterial infusion of doxorubicin during hemodynamic isolation of the liver (the Delcath system) was conducted to: 1) study the pharmacokinetics of regional doxorubicin therapy, and 2) define therapeutic efficacy in the treatment of unresectable liver tumors. Eighteen patients with unresectable primary or metastatic tumor in the liver were treated with 57 procedures. Pharmacokinetic studies were performed on all treatments. Hepatic extraction ratio of doxorubicin remained constant at 60.3+/-12.1%. independent of the dose escalation. The calculated intrahepatic concentration of doxorubicin ranged from 30 to 88 microg/ml when the dosage of doxorubicin was escalated from 50 to 120 mg/m2. Dose-limiting systemic toxicity (grade 4 myelosuppression) was observed at 120 mg/m2. Twelve of 14 patients who received more than one treatment at 90 or 120 mg/m2 were evaluable for disease response: there were 4 partial responses, 3 minor responses, I stable disease, and 4 progressive disease. The median overall survival of responders was 23 months, and for nonresponders it was 8 months. We have demonstrated a dose-response effect of hepatic infusion of doxorubicin at 90 and 120 mg/m2 in advanced hepatic malignancies. <b>The isolated hepatic perfusion system improves the therapeutic index of doxorubicin and provides pharmacologic justification for its use in the treatment of unresectable hepatic malignancies, especially metastatic melanoma and sarcoma.</b> 
&&url PMID: 10905565  


Liver Transpl Surg. 1999 Jan;5(1):65-80.  
<b>Management of hepatic metastases.</b>
Choti MA, Bulkley GB.
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Although the liver is the most common site of metastatic disease from a variety of tumor types, isolated hepatic metastases most commonly occur from colorectal cancer and, less frequently, from neuroendocrine tumors, gastrointestinal sarcoma, ocular melanoma, and others. Complete evaluation of the extent of metastatic disease, both intrahepatically and extrahepatically, is important before considering treatment options. Based on a preponderance of uncontrolled studies for hepatic metastatic colorectal carcinoma, surgical resection offers the only potential for cure of selected patients with completely resected disease, with 5-year survival rates of 25% to 46%. <b>Systemic and hepatic arterial infusion chemotherapy may be useful treatment options in patients with unresectable disease</b> and possibly as an adjuvant treatment after liver resection. Other techniques of local tumor ablation, including cryotherapy and radiofrequency ablation, although promising, remain unproved. Management of hepatic metastases from neuroendocrine tumors and other noncolorectal primary tumors should be individualized based on the patient's clinical course, extent of disease, and symptoms.  
&&url PMID: 9873095  


Oncology (Huntingt) 2000 Dec;14(12 Suppl 11):48-51 
<b>Intrahepatic therapy for resected hepatic metastases from colorectal carcinoma. </b>
Alberts SR. Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA. alberts.steven@mayo.edu 

A significant number of patients with colorectal cancer will present with hepatic metastases as their only site of metastatic disease. Surgical resection in patients with a limited number of metastases will lead to long-term survival in up to one-third. However, following surgery, many of these patients will relapse within the liver, and many will develop extrahepatic metastases. The use of hepatic artery infusion alternating with systemic therapy has proven to reduce the risk of recurrent disease and improve survival... Publication Types: Review Review, tutorial 
&&url PMID: 11204664 [PubMed - indexed for MEDLINE 


Recent Results Cancer Res 1998;147:3-12 
<b>Are there indications for intraarterial hepatic chemotherapy or isolated liver perfusion? The case of liver metastases from colorectal cancer. </b>
Rougier P. Service d'hepato-gastroenterologie, Hopital Ambroise Pare, Boulogne, France. 

Intraarterial hepatic chemotherapy (IAHC) has been used for many years to treat liver tumors (primary or secondary) if no extrahepatic extension exists, when no resection is feasible, and when no active systemic chemotherapy is available. Liver metastases from colorectal cancer represent one of the best indications, and many trials have demonstrated that IAHC is an efficient treatment. .... Liver toxicity and extrahepatic progression are the two main limiting factors that can be reduced using new protocols and combinations with systemic chemotherapy. ... Isolated liver perfusion adds to IAHC an extracorporal extraction and allows the use of higher doses of chemotherapy. Its efficacy has been suggested in small phase II trials; however, its relative complexity and the lack of clear demonstration of its efficacy compared to the most recent and effective systemic chemotherapies used alone or in combination with IAHC prevent the recommendation of its use outside clinical trials. IAHC and isolated liver perfusion are two active locoregional treatments that can be combined with surgical resection and/or systemic chemotherapy ... 
&&url PMID: 9670263 


Ann Ital Chir 1996 Nov-Dec;67(6):793-7 
[Locoregional chemotherapy of liver metastasis from colorectal carcinoma]. [Article in Italian] 
Zamparelli G, Pancera G, Pessi MA, Dallavalle G, Pirovano M, Valsecchi R, Labianca R, Samori G, Luporini G. Divisione Oncologia Medica, Azienda Ospedaliera San Carlo Borromeo di Milano. 
Hepatic metastases are a major cause of death in patients with colorectal carcinoma. Traditional intravenous chemotherapy produces responses in 10% to 30% of patients and surgical resection is feasible in approximately 20% of patients. Infusion of cytotoxic agents into the hepatic artery is the most promising form of therapy for unresectable hepatic metastases. The recent development of a totally implantable pump has allowed prolonged infusion of chemotherapeutic agents with a good compliance and quality of life of the patients. The rationale for hepatic arterial infusion (HAI) present an anatomical and pharmacological basis with the use of agents with high hepatic extraction resulting in minimal systemic toxicity. ... 
&&url PMID: 9214270 


Ann Surg Oncol 2000 Aug;7(7):490-5 
<b>Surgery after downstaging of unresectable hepatic tumors with intra-arterial chemotherapy. </b>
Meric F, Patt YZ, Curley SA, Chase J, Roh MS, Vauthey JN, Ellis LM. 
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. 

... This retrospective study was performed to assess the outcome among patients who underwent hepatic resection or tumor ablation after hepatic artery infusion (HAI) therapy down-staged previously unresectable hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (CRC). ... CONCLUSIONS: Hepatic resection or ablation after tumor downstaging with HAI therapy is a viable option for patients with unresectable HCC. However, given the high rate of recurrence of metastases from CRC, hepatic resection or ablation after downstaging with HAI should be used with caution. 
&&url PMID: 10947016 


Zhonghua Zhong Liu Za Zhi 1996 Sep;18(5):365-7 
<b>[The clinical efficacy of hepatic artery infusion chemotherapy and chemoembolization in the treatment of liver metastases]. [Article in Chinese] </b>
Zeng X, Wang S, Wei C. 
Department of Radiology, Wuhan General Hospital of Guangzhou Miliary Region. 

The efficacy and clinical experience of transcatheter hepatic artery infusion chemotherapy alone or chemoembolization in 118 patients with hepatic metastases were reviewed. Hepatic arterial infusion chemotherapy followed by embolization with lipiodol suspension and gelatin sponge pieces was carried out in 72 cases, infusion chemotherapy followed by embolization with lipiodol suspension in 32, and arterial infusion chemotherapy alone in 14. The results showed that the clinical efficacy of the first method was the best while that of the third method was the worst. The best effect was seen in patients with the single and hypervascular metastatic focus. The overall survival rate was 86.0%, 25.0%, 3.0% in 1 year, 3 years and 5 years, respectively. 
&&url PMID: 9387277 

