Preoperative radiologic and postoperative pathologic risk factors for early intra-hepatic recurrence in hepatocellular carcinoma patients who underwent curative resection

Abstract

Purpose: The risk of hepatocellular carcinoma (HCC) recurrence must be considered ahead of surgery. This study was undertaken to identify pre-operative risk factors for early intrahepatic recurrence of HCC after curative resection in a large-scale.

Materials and methods: We retrospectively reviewed the preoperative three-phase multi-detector CT (MDCT) and laboratory data for 240 HCC patients who underwent curative resection; tumor size, number, gross shape, capsule integrity, distinctiveness of tumor margin, portal vein thrombosis (PVT), alpha-fetoprotein level (AFP), and protein induced by vitamin K absence-II (PIVKA-II) levels were assessed. Surgical pathology was reviewed; tumor differentiation, capsule, necrosis, and micro-vessel invasion were recorded.

Results: HCC recurred in 61 patients within six months (early recurrence group), but not in 179 patients (control group). In univariate analysis, large tumor size (p = 0.018), shape (p = 0.028), poor capsule integrity (p = 0.046), elevated AFP (p = 0.015), and PIVKA-II (p = 0.008) were significant preoperative risk factors. Among the pathologic features, PVT (p = 0.023), Glisson's capsule penetration (p = 0.033), microvascular invasion (p < 0.001), and poor differentiation (p = 0.001) showed statistical significance. In multivariate analysis, only the histopathologic parameters of microvascular invasion and poor differentiation achieved statistical significance.

Conclusion: Preoperative CT and laboratory parameters showed limited value, while the presence of microscopic vascular tumor invasion and poorly differentiated HCC correlated with higher risk of early recurrence after curative resection.

Keywords: Hepatocellular carcinoma; curative resection; early recurrence; postoperative pathologic findings; preoperative CT.

Fig. 1

A 56-year-old female with early recurrent HCC after segmentectomy. The AFP level in a blood sample obtained on the same day as the CT scan was 1076.84 IU/mL. (A) Arterial phase of the preoperative CT obtained by a 4-slice MDCT. A mass measuring approximately 2.2 cm in diameter which was later proven by surgery to be hepatocellular carcinoma is observed at the dome of the liver, presenting as a multinodular confulent nodule (arrow). (B) Early washout (arrow) of contrast of this nodule is observed during the portal venous phase, an enhancement pattern consistent with HCC. (C) The equilibrium phase of the preoperative CT. A linear enhancement structure (black arrow) was noted which was considered to be the radiological capsule. The radiological capsule was assessed to cover less than 25% of the tumor circumference (capsule grade 4). The margin of the nodule is poorly defined (white arrow). (D) Microscopic findings show high grade (Edmondson-Steiner grade III) hepatocellular carcinoma; original magnification, ×200; hematoxylin-eosin (H & E). (E) Microscopic examination revealed frequent microvessel tumor invasion (white arrows), original magnification, ×200; hematoxylin-eosin (H & E). (F) Marked increase of AFP level (10865.27 IU/mL) was observed at the fifth postoperative-month blood test. He underwent a CT scan, which revealed an infiltrative hypervascular mass (white arrow). Another 1 cm sized hypervascular nodule (black arrow) is noted, which increased further in size and measured to be 2.2 cm at a CT scan performed 4 months afterwards, and the findings were highly suggestive of a HCC nodule. HCC, hepatocellular carcinoma; MDCT, multi-detector CT.