Purpose: To test whether ischemia resistance is present in individuals with NRF2-mutated HCC and if this resistance can be overcome by means of NRF2 inhibition in HCC cell lines. Materials and Methods:This was a combined retrospective review of an institutional database (from January 2011 to December 2018) and prospective study (from January 2014 to December 2018) of participants with HCC who underwent TAE and a laboratory investigation of HCC cell lines. Imaging follow-up included liver CT or MRI at 1 month after the procedure followed by 3-month interval scans. Tumor radiologic response was assessed on the basis of follow-up imaging. The time to local progression after TAE for individuals with and individuals without NRF2 pathway alterations was estimated by using competing risk analysis (Gray test). The in vitro response to ischemia in four HCC cell lines with and without NRF2 overexpression was evaluated, and the combination of ischemia with NRF2 knockdown by means of short hairpin RNA or an NRF2 inhibitor was tested. Doubling time estimates, dose response curve regression, and comparison analyses were performed.Results: Sixty-five individuals (median age, 69 years [range, 19-84 years]; 53 men) were evaluated. HCCs with NRF2 pathway mutation had a shorter time to local progression after TAE compared to those without mutation (6-month cumulative incidence of local progression, 56% [range, 19%-91%] vs 22% [range, 12%-34%], respectively; P , .001) and confirmed ischemia resistance in NRF2-overexpressing HCC cell lines. However, ischemia and NRF2 knock-down worked synergistically to decrease proliferation of NRF2-overexpressing HCC cell lines. Dose response curves of ML385, an NRF2 inhibitor, showed that ischemia induces addiction to NRF2 in cells with NRF2 alterations. Conclusion:Hepatocellular carcinoma with nuclear factor E2-related factor 2 (NRF2) alterations showed resistance to ischemia, but ischemia simultaneously induced sensitivity to NRF2 inhibition.

Pulmonary metastasectomy has become an established mode of therapy in the management of certain patients with metastatic colorectal cancer. All patients undergoing pulmonary resection for metastatic colorectal cancer between March 2008 and February 2014 were studied. 190 patients were identified. Most had a single metastasis (83%); 17% had multiple lesions (maximum: 4). The approach was thoracotomy in 92 and VATS in 98. 67% underwent wedge resection and 33% lobectomy. The size of the resected lesions was 8-110 mm (median: 24). 13% of patients underwent more than one procedure (maximum: 4); 8% had prior hepatic metastasectomy. There was no operative mortality. The 1-, 3- and 5-year survival was 92, 87 and 82%, respectively. Guidelines for referral and follow-up of these patients should be developed.

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