Background & Aims-Hepatocellular carcinoma (HCC) recurs in approximately 70% of cases after resection. Vascular invasion by tumor cells can be classified as gross or microscopic (mVI) and is a risk factor for recurrence. We examined a large cohort of patients with HCC that were treated by resection to identify features of microvascular invasion that correlated with recurrence and survival.
Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCRseq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and immune cells. We investigate how these interactions reflect intra-tumor heterogeneity (ITH) by correlating regional neo-epitope and viral antigen burden with the regional adaptive immune response. Regional expression of passenger mutations dominantly recruits adaptive responses as opposed to hepatitis B virus and cancer-testis antigens. We detect different clonal expansion of the adaptive immune system in distant regions of the same tumor. An ITH-based gene signature improves singlebiopsy patient survival predictions and an expression survey of 38,553 single cells across 7 regions of 2 patients further reveals heterogeneity in liver cancer. These data quantify transcriptomic ITH and how the different components of the HCC ecosystem interact during cancer evolution.
Long-term survival after pancreatic resection for metastatic disease is achievable, and patients with primary renal cell carcinoma seem to have a more favorable prognosis. Surgical resection should thus be offered to selected patients with isolated metastatic disease to the pancreas.
Background:This study aims to evaluate the impact of liver fibrosis severity on prognosis following liver resection among HBV–HCC patients.Methods:Data were extracted from a prospective database of 189 HBV–HCC patients treated at Mount Sinai between 1995 and 2008. Fibrosis staging of each surgical resection specimen using the modified Ishak method was performed by a single liver pathologist.Results:A wide range of Ishak fibrosis stage was observed among this patient population, with 29% having established cirrhosis (Ishak stage 6). Ishak stage 6 was independently associated with poor overall and recurrence-free survival. In patients with Ishak stage 1–5, Ishak stage did not affect survival; rather, tumour size was associated with poor overall survival, and tumour size, histologic activity index and serum AFP>20 ng ml−1 were associated with poor recurrence-free survival. In patients with Ishak stage 6, poorly differentiated histology and tumour size were associated with poor overall survival, and tumour size was associated with poor recurrence-free survival.Conclusion:HBV–HCC develops with varying degrees of underlying liver fibrosis; however, progressive liver fibrosis does not affect the outcomes following resection until cirrhosis is reached. Established cirrhosis, as defined histologically by Ishak stage 6, is an independent predictor of poor overall and recurrence-free survival among these patients.
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