Modern trends in minimally invasive versus open hepatectomy for colorectal liver metastasis: an analysis of ACS-NSQIP.

BACKGROUND: Surgical resection of colorectal liver metastasis (CRLM) provides the best opportunity for prolonged survival. Eligibility for metastasectomy has expanded with technical advancements including parenchymal-sparing hepatectomy (PSH). Meanwhile, enthusiasm for minimally invasive surgery (MIS) has increased, though this approach may be preferentially utilized for technically straightforward cases. The purpose of this study is to characterize modern trends in open versus MIS approaches to partial hepatectomy and anatomic hepatectomy for CRLM within a nationwide cohort. METHODS: The American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) was used to investigate trends in MIS versus open hepatectomy for CRLM from 2015 to 2019. We examined baseline clinicopathologic and disease-related characteristics and compared trends in treatments over the study period. RESULTS: A total of 7457 patients undergoing hepatectomy for CRLM were identified (1367 MIS, 6090 open). Patients had similar clinicopathologic features between the two groups. Patients undergoing MIS resection less frequently received neoadjuvant therapy (51.1% vs 64.0%, p < 0.001) or concurrent intraoperative ablation (15.0% vs 21.3%, p < 0.001). Patients with tumors < 2 cm (34.9% vs 26.8%, p < 0.001) or only one to two tumors (82.8% vs 65.0%, p < 0.001) more commonly underwent MIS. MIS and open partial hepatectomies both significantly increased over the study period, but open partial hepatectomy increased at a greater rate than MIS (p < 0.001). Rates of anatomic resections have remained the same, with a greater proportion performed using an open approach (34.9% vs 16.4%, p < 0.001). Rates of operations consisting of > 1 concurrent partial hepatectomy are stable, but significantly more likely to be performed open (p < 0.001). CONCLUSIONS: Hepatectomy for CRLM has increased from a rise in partial hepatectomy, potentially translating to increased use of PSH. Current trends suggest MIS approaches appear to be increasing, but selectively implemented for patients with less technically demanding disease characteristics. Educational efforts should be directed towards increased dissemination of parenchymal-sparing MIS techniques for more complex resections.

Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in neuroblastoma, a devastating pediatric cancer of the sympathetic nervous system. Germline and somatically acquired ALK aberrations induce increased autophosphorylation, constitutive ALK activation and increased downstream signaling. Thus, ALK is a tractable therapeutic target in neuroblastoma, likely to be susceptible to both small-molecule tyrosine kinase inhibitors and therapeutic antibodies-as has been shown for other receptor tyrosine kinases in malignancies such as breast and lung cancer. Small-molecule inhibitors of ALK are currently being studied in the clinic, but common ALK mutations in neuroblastoma appear to show de novo insensitivity, arguing that complementary therapeutic approaches must be developed. We therefore hypothesized that antibody targeting of ALK may be a relevant strategy for the majority of neuroblastoma patients likely to have ALK-positive tumors. We show here that an antagonistic ALK antibody inhibits cell growth and induces in vitro antibody-dependent cellular cytotoxicity of human neuroblastoma-derived cell lines. Cytotoxicity was induced in cell lines harboring either wild type or mutated forms of ALK. Treatment of neuroblastoma cells with the dual Met/ALK inhibitor crizotinib sensitized cells to antibody-induced growth inhibition by promoting cell surface accumulation of ALK and thus increasing the accessibility of antigen for antibody binding. These data support the concept of ALK-targeted immunotherapy as a highly promising therapeutic strategy for neuroblastomas with mutated or wild-type ALK.