Hepatic arterial infusion (HAI) is a medical procedure that delivers chemotherapy directly to the liver. The procedure, mostly used in combination with systemic chemotherapy, plays a role in the treatment of liver metastases in patients with colorectal cancer (CRC).[1] Although surgical resection remains the standard of care for these liver metastases, majority of patients have lesions that are unresectable.
The liver derives its blood supply from two sources – via the hepatic arterial circulation and the portal circulation. Liver metastases get most of their blood supply primarily from the hepatic artery, whereas the normal liver cells get their blood supply from the portal circulation.[2] This allows for chemotherapeutic drugs to be delivered directly to the cancer cells if infused into the hepatic artery.
Multiple trials have compared HAI (with various chemotherapeutic agents) to systemic chemotherapy. Compared to systemic Fluoropyrimidine, HAI with Floxuridine (FUDR) had an increased response, but there was no overall increase in patient survival.[3][4][5][6][7] Efforts have been made to increase the efficacy and safety of HAI chemotherapy: when a combination of FUDR and dexamethasone was used for HAI, both response rate and median survival increased.[8] In another study, a combination of FUDR and leucovorin for HAI increased the response rate, and reduced the biliary toxicity seen with the use of FUDR alone.[9]
Considering improvements in the surgical placement of the HAI pump and studies showing promising results when HAI therapy is used together with systemic oxaliplatin or irinotecan,[10][11] there is once again an increased interest in the role of HAI as a treatment option in patients with cancer, who have unresectable CRC liver metastases. However, studies recommend that this treatment modality be restricted to centers with expertise in the surgical placement of these pumps, and the technical aspects of localized chemotherapy.
^Karanicolas PJ, Metrakos P, Chan K, Asmis T, Chen E, Kingham TP, Kemeny N, Porter G, Fields RC, Pingpank J, Dixon E (Feb 2014). "Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement". Current Oncology. 21 (1): e129–e136. doi:10.3747/co.21.1577. PMC 3921037. PMID 24523610.
^Breedis C, Young G (September–October 1954). "The blood supply of neoplasms in the liver". The American Journal of Pathology. 30 (5): 969–77. PMC 1942491. PMID 13197542.
^Allen-Mersh TG, Earlam S, Fordy C, Abrams K, Houghton J (5 November 1994). "Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases". The Lancet. 344 (8932): 1255–60. doi:10.1016/S0140-6736(94)90750-1. PMID 7526096. S2CID 35318063.
^Chang AE, Schneider PD, Sugarbaker PH, Simpson CO, Culnane MA, Steinberg SM (December 1987). "A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases". Annals of Surgery. 206 (6): 685–93. doi:10.1097/00000658-198712000-00001. PMC 1493315. PMID 2961314.
^Hohn DC, Stagg RJ, Friedman MA, Hannigan Jr JF, Rayner A, Ignoffo RJ, Acord P, Lewis BJ (November 1989). "A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial". Journal of Clinical Oncology. 7 (11): 1646–54. doi:10.1200/JCO.1989.7.11.1646. PMID 2530317.
^Kemeny N, Daly J, Reichman B, Geller N, Botet J, Oderman P (1 October 1987). "Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma: a randomized trial". Annals of Internal Medicine. 107 (4): 459–465. doi:10.7326/0003-4819-107-4-459. PMID 2957943.
^Kemeny N, Seiter K, Niedzwiecki D, Chapman D, Sigurdson E, Cohen A, Botet J, Oderman P, Murray P (15 January 1992). "A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer". Cancer. 69 (2): 327–34. doi:10.1002/1097-0142(19920115)69:2<327::AID-CNCR2820690209>3.0.CO;2-U. PMID 1303612.
^Kemeny N, Seiter K, Conti JA, Cohen A, Bertino JR, Sigurdson ER, Botet J, Chapman D, Mazumdar M, Budd AJ (15 February 1994). "Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinoma". Cancer. 73 (4): 1134–42. doi:10.1002/1097-0142(19940215)73:4<1134::AID-CNCR2820730403>3.0.CO;2-V. PMID 8313315.
^Kemeny N, Jarnagin W, Paty P, Gönen M, Schwartz L, Morse M, Leonard G, D’Angelica M, DeMatteo R, Blumgart L, Fong Y (1 August 2005). "Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer". Journal of Clinical Oncology. 23 (22): 4888–96. doi:10.1200/JCO.2005.07.100. PMID 16009951.
^Dhir M, Jones HL, Shuai Y, Clifford AK, Perkins S, Steve J, Hogg ME, Choudry MH, Pingpank JF, Holtzman MP, Zeh HJ (1 January 2017). "Hepatic Arterial Infusion in Combination with Modern Systemic Chemotherapy is Associated with Improved Survival Compared with Modern Systemic Chemotherapy Alone in Patients with Isolated Unresectable Colorectal Liver Metastases: A Case–Control Study". Annals of Surgical Oncology. 24 (1): 150–8. doi:10.1245/s10434-016-5418-6. PMID 27431415. S2CID 21499263.
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