Patients without evidence of extrahepatic disease, <4 metastases and in whom a negative resection margin is achievable are resected with curative intent. In patients with ≥4 metastases the operation is still considered potentially curative but recurrence rates are high. If technically resectable, these patients are offered resection but we are more likely to treat with a brief

course of chemotherapy prior to resection. Patients with resectable extrahepatic disease, and those in which a margin is likely to be positive on final pathology have a nearly universal rate of recurrence but may still benefit Inhibitors,research,lifescience,medical from resection. Unfortunately, margin status is not completely predictable based on preoperative imaging and therefore this issue cannot reliably be used to exclude patients from resection. Nonetheless, if the margin is very likely to be involved due to tumor abutment of vascular structures that must Inhibitors,research,lifescience,medical be preserved we feel it is reasonable to treat with systemic and/or regional chemotherapy prior to resection in hope of achieving response and decreasing

the chance of a positive margin. Concurrent resection of all extrahepatic disease in Inhibitors,research,lifescience,medical well selected patients is associated with the possibility of long-term survival at our institution but patients are highly selected. Currently, we restrict such resections to patients with limited, resectable single sites of extrahepatic disease who have stable or responsive Inhibitors,research,lifescience,medical disease on chemotherapy (71). There are numerous reasons to justify the use of preoperative systemic chemotherapy. Preoperative chemotherapy may increase the R0 resection rate while preserving remnant liver parenchyma, treat unrecognized microscopic disease and be used as a test of chemoresponsiveness. Modern chemotherapy with fluorouracil Inhibitors,research,lifescience,medical (FU), leucovorin and oxaliplatin or irinotecan have improved response rates over the last decade and offer the possibility of converting unresectable to resectable disease. Studies have demonstrated meaningful

conversion rates between 14-41% with systemic chemotherapy alone (9,72). Our institution offers hepatic artery infusional (HAI) therapy with floxuridine and dexamethasone combined with systemic chemotherapy for patients with extensive liver disease not amenable to resection. When systemic chemotherapy is combined first with HAI, 47% of initially deemed unresectable patients were eventually PCI-32765 ic50 converted to resectable at our institution with promising long-term outcomes (73). Using neoadjuvant chemotherapy for resectable disease (<4 metastases, no extrahepatic disease and technically resectable with clear margins) is debatable. Many argue that progression on chemotherapy portends a poor prognosis after resection and neoadjuvant chemotherapy is a strategy to identify such patients. Adam et al.