Radiofrequency ablation (RFA) is recommended as a first-line therapy for small hepatocellular carcinoma (HCC). Tumor location is a potential factor influencing the procedure of RFA. To compare oncologic outcomes of RFA for different tumor locations, this retrospective study enrolled 194 patients with small HCC who had undertaken RFA. The HCC nodules were classified as peri-hepatic-vein (pHV) or non-pHV, peri-portal-vein (pPV) or non-pPV, and subcapsular or non-subcapsular HCC. The regional recurrence-free survival (rRFS), overall survival (OS), recurrence-free survival (recurrence in any location, RFS) and distant recurrence-free survival (dRFS) were compared. Operation failures were recorded in five pPV HCC patients, which was more frequent than in non-pPV HCC patients (p = 0.041). The 1-, 3-, and 5-year rRFS was 68.7%, 53.7%, and 53.7% for pHV patients and 85.1%, 76.1%, and 71.9% for non-pHV patients, respectively (p = 0.012). After propensity score matching, the 1-, 3-, and 5-year rRFS was still worse than that of non-pHV patients (p = 0.013). The OS, RFS, and dRFS were not significantly different between groups. Conclusions: A pHV location was a risk factor for the regional recurrence after RFA in small HCC patients. The tumor location may not influence OS, RFS, and dRFS. Additionally, a pPV location was a potential high-risk factor for incomplete ablation.

Cancer immunotherapy restores or enhances the effector function of T cells in the tumor microenvironment, but the efficacy of immunotherapy has been hindered by therapeutic resistance. Here, we identify the proto-oncogene serine/threonine protein kinase PIM2 as a novel negative feedback regulator of IFNγ-elicited tumor inflammation, thus endowing cancer cells with aggressive features. Mechanistically, IL1β derived from IFNγ-polarized tumor macrophages triggered PIM2 expression in cancer cells via the p38 MAPK/Erk and NF-κB signaling pathways. PIM2+ cancer cells generated by proinflammatory macrophages acquired the capability to survive, metastasize, and resist T-cell cytotoxicity and immunotherapy. A therapeutic strategy combining immune checkpoint blockade (ICB) with IL1β blockade or PIM2 kinase inhibition in vivo effectively and successfully elicited tumor regression. These results provide insight into the regulatory and functional features of PIM2+ tumors and suggest that strategies to influence the functional activities of inflammatory cells or PIM2 kinase may improve the efficacy of immunotherapy. Significance: Cross-talk between T cells and macrophages regulates cancer cell PIM2 expression to promote cancer aggressiveness, revealing translational approaches to improve response to ICB in hepatocellular carcinoma.

Background: Patients with hepatocellular carcinoma (HCC) undergoing surgical resection still have a high 5‐year recurrence rate (~ 60%). With the development of laparoscopic hepatectomy (LH), few studies have compared the efficacy between LH and traditional surgical approach on HCC. The objective of this study was to establish a nomogram to evaluate the risk of recurrence in HCC patients who underwent LH. Methods: The clinical data of 432 patients, pathologically diagnosed with HCC, underwent LH as initial treatment and had surgical margin > 1 cm were collected. The significance of their clinicopathological features to recurrence‐free survival (RFS) was assessed, based on which a nomogram was constructed using a training cohort ( n = 324) and was internally validated using a temporal validation cohort ( n = 108). Results: Hepatitis B surface antigen (hazard ratio [HR], 1.838; P = 0.044), tumor number (HR, 1.774; P = 0.003), tumor thrombus (HR, 2.356; P = 0.003), cancer cell differentiation (HR, 0.745; P = 0.080), and microvascular tumor invasion (HR, 1.673; P =0.007) were found to be independent risk factors for RFS in the training cohort, and were used for constructing the nomogram. The C‐index for RFS prediction in the training cohort using the nomogram was 0.786, which was higher than that of the 8th edition of the American Joint Committee on Cancer TNM classification (C‐index, 0.698) and the Barcelona Clinic Liver Cancer staging system (C‐index, 0.632). A high consistency between the nomogram prediction and actual observation was also demonstrated by a calibration curve. An improved predictive benefit in RFS and higher threshold probability of the nomogram were determined by receiver operating characteristic curve analysis, which was also confirmed in the validation cohort compared to other systems. Conclusions: We constructed and validated a nomogram able to quantify the risk of recurrence after initial LH for HCC patients, which can be clinically implemented in assisting the planification of individual postoperative surveillance protocols.

Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma (HCC). However, few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy. The present prospective study compared the clinical efficacy of laparoscopic surgery with conventional open surgery in HCC patients with postoperative tumor recurrence. We conducted a prospective study of 64 patients, all of whom had undergone open surgery once before, who were diagnosed with recurrent HCC between June 2014 and November 2014. The laparoscopic group (n = 31) underwent laparoscopic hepatectomy, and the control group (n = 33) underwent conventional open surgery. Operation time, intraoperative blood loss, surgical margins, postoperative pain scores, postoperative time until the patient could walk, anal exsufflation time, length of hospital stay, and inpatient costs were compared between the two groups. The patients were followed up for 1 year after surgery, and relapse-free survival was compared between the two groups. All surgeries were successfully completed. No conversion to open surgery occurred in the laparoscopic group, and no serious postoperative complications occurred in either group. No significant difference in inpatient costs was found between the laparoscopic group and the control group (P = 0.079), but significant differences between the two groups were observed for operation time (116.7 ± 37.5 vs. 148.2 ± 46.7 min, P = 0.031), intraoperative blood loss (117.5 ± 35.5 vs. 265.9 ± 70.3 mL, P = 0.012), postoperative time until the patient could walk (1.6 ± 0.6 vs. 2.2 ± 0.8 days, P < 0.05), anal exsufflation time (2.1 ± 0.3 vs. 2.8 ± 0.7 days, P = 0.041), visual analogue scale pain score (P < 0.05), postoperative hepatic function (P < 0.05), and length of hospital stay (4.5 ± 1.3 vs. 6.0 ± 1.2 days, P = 0.014). During the 1-year postoperative follow-up period, 6 patients in each group had recurrent HCC on the side of the initial operation, but no significant difference between groups was observed in the recurrence rate or relapse-free survival. In the laparoscopic group, operation time, postoperative time until the patient could walk, anal exsufflation time, and inpatient costs were not different (P > 0.05) between the patients with contralateral HCC recurrence (n = 18) and those with ipsilateral HCC recurrence (n = 13). However, intraoperative blood loss was significantly less (97.7 ± 14.0 vs. 186.3 ± 125.6 mL, P = 0.012) and the hospital stay was significantly shorter (4.2 ± 0.7 vs. 6.1 ± 1.7 days, P = 0.021) for the patients with contralateral recurrence than for those with ipsilateral recurrence. For the patients who previously underwent conventional open surgical resection of HCC, complete laparoscopic resection was safe and effective for recurrent HCC and resulted in a shorter operation time, less intraoperative blood loss, and a faster postoperative recovery than conventional open surgery. Laparoscopic resection was especially advantageous for the patients with contralateral HCC recurrence.