This study evaluates the survival benefit and safety of hepatectomy after down-staging by 3-dimensional conformal radiation therapy (3D-CRT) for major portal vein tumor thrombus (PVTT) combined with hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC). Fifty-two patients with unresectable advanced HCC treated with HAIC combined with 3D-CRT for PVTT, from January 2002 to March 2015, were analyzed in this retrospective study. Hepatectomy was offered to patients if, based on radiologic findings, all gross lesions were considered resectable. The safety of hepatectomy was investigated and overall survival (OS) was compared between the resection group (n = 7) and non-resection group (n = 43). OS was significantly higher in the resection group than in the non-resection group. Results of multivariate analysis identified conversion to surgery (hazard ratio, 0.35; 95% confidence interval, 0.10-0.99; P = 0.048) as an independent factor influencing OS. There were no serious postoperative complications and no case of mortality in patients who underwent hepatectomy. Our findings suggest that hepatectomy after down-staging by 3D-CRT for PVTT combined with HAIC for advanced HCC is safe and results in good long term outcome.

The utility of glypican-3 (GPC3) expression for the detection of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) patients has not been elucidated. The aim of this study was to identify associations between the presence of GPC3-positive CTCs and clinicopathological factors of these patients, furthermore, to evaluate whether CTC can predict microscopic portal vein invasion (mPVI). This study was done on 85 patients who underwent hepatectomy as the first-line treatment and whose preoperative imaging showed no evidence of macroscopic PVI and distant metastases. Peripheral blood was collected from all patients immediately before surgery. Cells were purified initially by density gradient centrifugation followed by immunomagnetic positive enrichment based upon the expression of GPC3. The numbers of CTCs contained in the enriched samples were enumerated via flow cytometry. Protocol validation using HepG2 cells spiked into 8.0 mL of blood from a healthy volunteer indicated that we were able to recover 12.1% of the tumor cells. A median number of 3 CTCs (range: 0–27) was detected in the 8.0 mL of peripheral blood of the 85 analyzed HCC patients. Thirty-three patients had CTCs ≥5, and these patients had a higher incidence of mPVI (p < 0.001), a lower disease-free survival (p = 0.015), and a lower overall survival (p = 0.047) than those with CTCs <5. Multivariate analysis identified CTCs ≥5 as an independent predictor of mPVI (p < 0.001). In conclusion, preoperative GPC3-positive CTCs ≥5 was a risk factor of mPVI and poor prognosis, and therefore may be a useful biomarker for HCC patient outcomes.

Aim: Although inflammation‐based markers in cancer have been used for prognostic prediction, the most useful marker for hepatocellular carcinoma (HCC) has not been established. We investigated the usefulness of various inflammation‐based markers in HCC patients after hepatectomy.Methods: A total of 478 patients who underwent initial hepatectomy for HCC from 2009 to 2015 and were diagnosed with pathological HCC were included in this retrospective study. Inflammation‐based markers consisted of the C‐reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, platelet to lymphocyte ratio and prognostic index. Univariate and multivariate analyses for overall survival (OS) and disease‐free survival (DFS) using the Cox proportional hazard model were carried out. Kaplan‐Meier analysis and log‐rank test were used for comparison of OS and DFS. To reduce influences of selection bias and confounders for stratifying CAR, clinicopathological characteristics of patients were balanced by propensity score matching.Results: Multivariate analysis identified only high CAR (>0.027) as an indicator of poor OS, and high CAR and high GPS (1‐2) as indicators of poor DFS among inflammation‐based markers. After propensity score matching, 124 patients each with low CAR and high CAR were matched. High CAR was correlated with both poor OS and DFS.Conclusion: C‐reactive protein to albumin ratio was the most valuable prognostic indicator after hepatectomy for HCC among inflammation‐based markers.