Aggressive surgical approach in patients with adrenal-only metastases from hepatocellular carcinoma enables higher survival rates than standard systemic therapy.

BACKGROUND: Although guidelines recommend systemic therapy even in patients with limited extrahepatic metastases from hepatocellular carcinoma (HCC), a few recent studies suggested a potential benefit for resection of extrahepatic metastases. However, the benefit of adrenal resection (AR) for adrenal-only metastases (AOM) from HCC was not proved yet. This is the first study to compare long-term outcomes of AR to those of sorafenib in patients with AOM from HCC. METHODS: The patients with adrenal metastases (AM) from HCC were identified from the electronic records of the institution between January 2002 and December 2018. Those who presented AM and other sites of extrahepatic disease were excluded. Furthermore, the patients with AOM who received other therapies than AR or sorafenib were excluded. RESULTS: A total of 34 patients with AM from HCC were treated. Out of these, 22 patients had AOM, 6 receiving other treatment than AR or sorafenib. Eventually, 8 patients with AOM underwent AR (AR group), while 8 patients were treated with sorafenib (SOR group). The baseline characteristics of the two groups were not significantly different in terms of age, sex, number and size of the primary tumor, timing of AM diagnosis, Child-Pugh and ECOG status. After a median follow-up of 15.5 months, in the AR group, the 1-, 3-, and 5-year overall survival rates (85.7%, 42.9%, and 0%, respectively) were significantly higher than those achieved in the SOR group (62.5%, 0% and 0% at 1-, 3- and 5-year, respectively) (P = 0.009). The median progression-free survival after AR (14 months) was significantly longer than that after sorafenib therapy (6 months, P = 0.002). CONCLUSIONS: In patients with AOM from HCC, AR was associated with significantly higher overall and progression-free survival rates than systemic therapy with sorafenib. These results could represent a starting-point for future phase II/III clinical trials.

Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma.

The complex regulation of tumor suppressive gene and its pseudogenes play key roles in the pathogenesis of hepatocellular cancer (HCC). However, the roles played by pseudogenes in the pathogenesis of HCC are still incompletely elucidated. This study identifies the putative tumor suppressor INTS6 and its pseudogene INTS6P1 in HCC through the whole genome microarray expression. Furthermore, the functional studies - include growth curves, cell death, migration assays and in vivo studies - verify the tumor suppressive roles of INTS6 and INTS6P1 in HCC. Finally, the mechanistic experiments indicate that INTS6 and INTS6P1 are reciprocally regulated through competition for oncomiR-17-5p. Taken together, these findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p. Our investigation of this regulatory circuit reveals novel insights into the underlying mechanisms of hepatocarcinogenesis.

Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas.

Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.