Arterial therapy of hepatic colorectal metastases

Abstract

Considerable experience of the treatment of irresectable hepatic colorectal metastases has accumulated over the past three decades. In this review, the rationale for hepatic artery treatment of colorectal metastases to the liver is presented and various access techniques and chemotherapeutic agents for infusion are discussed. Randomized trials of hepatic artery chemotherapy (HAC) are analysed, and the promising results of recent studies combining less toxic and more effective agents are summarized. Continuous infusion pumps provide the most reliable and long-lasting access for HAC. Appropriate surgical techniques and medical management can minimize complications. Although tumour progression is best controlled by HAC, a clear-cut survival advantage has yet to be demonstrated. While hepatic artery infusion chemotherapy cannot yet be recommended outside investigational protocols, the experience gained so far should stimulate further studies.

Multiple bilobar liver metastases: cryotherapy for residual lesions after liver resection

“…Although this is not a control study, survival would seem to be considerably better than the survival of patients treated by hepatic artery chemotherapy alone, where median survival of <18 months has been seen in almost all series [16,17]. Clearly, survival in our patients is superior to the median survival of only 6-12 months reported for unselected patients with untreated bilobar metastases [6,18,19].…”

“…We were also encouraged by the long-term, disease-free interval in a few patients. In fact, the relatively good survival of 88% at 1 year and 60% at 2 years is similar to that after curative liver resection [4,7,17,20]. Longer follow-up should allow us to make more meaningful comparisons.…”

Crystal Structure of Yeast Cytosine Deaminase

“…The bacterial and fungal CDs are distinct from each other and have evolved separately. The 426-residue hexameric Escherichia coli enzyme like the murine adenosine deaminase belongs to the (␤/␣) 8 -barrel amidohydrolase superfamily, in which four histidines and one aspartate located at similar spatial positions are conserved for metal coordination and enzyme catalysis (2)(3)(4). On the other hand, the 158-residue dimeric yeast counterpart may share two conserved signature sequences, HXE and CXXC, with a variety of deaminases, and thus has been grouped into the cytidine and deoxycytidylate deaminase family in the Pfam protein family data base (5,6).…”

“…The antimetabolite 5-fluorouracil (5-FU) is one of the most active chemotherapeutic agents for the treatment of colorectal cancer, but it has limited efficacy due to gastrointestinal and hematological toxicities (8). Because of its ability to convert the relatively nontoxic 5-fluorocytosine (5-FC) into 5-FU and its absence in mammalian cells, CD has become an attractive candidate for the reduction of 5-FU toxicity toward normal distal tissues in enzyme-prodrug gene therapy (9).…”

Development of a hypoxia-inducible cytosine deaminase expression vector for gene-directed prodrug cancer therapy

“…28 However, the efficacy of systemic treatment with 5-FU is limited by gastrointestinal and hematological toxicities. 29 Dachs et al 30 used a three-copy HRE and PGK promoter-controlled gene construct to preferentially express bacterial CD in HT1080 fibrosarcoma cells under anoxic conditions, showing a 6.8-fold induction as compared to aerobic cells. The transfected cells also were more sensitive to 5-FC treatment under anoxia, exhibiting IC 50 values of 34 and 6.3 mM 5-FC for aerobic and anoxic conditions, respectively.…”