Serological and histological indices of hepatocellular carcinoma and tumor volume doubling time

Abstract

Hepatocellular carcinoma (HCC) frequently develops in cirrhotic liver and is one of the most common malignancies worldwide. The tumor volume doubling time (TVDT) reflects the natural tumor growth rate and is an indicator of the biological malignant potential of a tumor. The present study aimed to elucidate the association between the serological and histological indices of HCC and TVDT. TVDT was analyzed for 53 HCCs by measuring the enlargement of the tumor diameter on dynamic computed tomography. Differences in TVDT were compared among histological grades of HCC differentiation. The α-fetoprotein (AFP) doubling time (T2AFP) for 44 HCCs with AFP levels >200 ng/ml was calculated and the differences in T2AFP were compared according to the histological grade of HCC differentiation and positivity for agglutinin-reactive fraction of α-fetoprotein (AFP-L3). Among these 44 HCCs, the correlation between T2AFP and TVDT was analyzed for the 27 tumors for which TVDT could be calculated. The mean ± standard deviation (SD) TVDT in Edmondson grade 1 (Ed1), Ed2 and Ed3 HCC was 138.3±110.3, 94.9±91.5 and 32.2±20.8 days, respectively (P<0.05). The mean ± SD T2AFP in Ed2 and Ed3 HCC was 121.0±167.5 and 37.3±24.6 days, respectively (P<0.01). TVDT and T2AFP decreased with histological dedifferentiation of HCC. The mean ± SD T2AFP in the AFP-L3-positive and -negative groups was 63.2±101.2 and 191.9±209.9 days, respectively, with a statistically significant difference between the groups (P<0.01). A significant correlation was observed between T2AFP and TVDT (correlation coefficient, 0.70; P<0.01). A significant correlation was also observed among TVDT, serological indices and histological grades of HCC differentiation. A short T2AFP and/or AFP-L3-positivity were shown to reflect a poorly differentiated HCC histopathology and a higher malignant potential.

Evidence Supporting LI-RADS Major Features for CT- and MR Imaging–based Diagnosis of Hepatocellular Carcinoma: A Systematic Review

“…The median TVDT in untreated primary HCCs is 178 days, while the median TVDT of recurrent HCCs after localregional treatment is 82 days (96). Well-differentiated HCCs tend to be slow growing, whereas moderately and poorly differentiated HCCs are fast growing, although there is overlap in the reported TVDTs of HCCs with varying degrees of differentiation (93,97,98). Imaging features associated with shorter TVDT include APHE (92,(99)(100)(101), presence of "washout" (100,102), T2 hyperintensity (99), and diameter less than 1 cm at baseline (94,103).…”

Role of abbreviated MRI protocol for screening of HCC in HCV related cirrhotic patients prior to direct-acting antiviral treatment

“…A retrospective study done by Piana et al [5] on 91 patients with 109 HCC assessing the sensitivity of DWI for detection of HCC in correlation with histopathology; two blinded readers assess HCC being hyper intense with a sensitivity of 89/109 (82%) and 79/109 (72%) and decreased to be sensitivity of 74% and 64% in tumors less than 20 mm, and there was an agreement between the two readers. Another cohort study done by Shingaki et al [13], focusing on small sized tumor (20 mm or less), found that sensitivity being 78.8% of HCC of 66 pathologically proven lesions were hyper intense to back ground liver. Another retrospective study by Zhao et al [14] made on HCC lesions and determined for lesions between 0.6 and 2 cm with an average size of 1.5 cm was visible on DWI with a sensitivity of 79%.…”

Diffusion‐weighted MRI for hepatocellular carcinoma screening in chronic liver disease: Direct comparison with ultrasound screening

“…These HCC's, however, are likely to be small and slow growing given that the doubling time of tumours is related to the level of differentiation which varies between 138 days to 32 days for Edmonson grade 1 and grade 3 tumours, respectively. 26 It was reassuring that no patient was found to have developed a new tumour in a follow-up period of at least 6 months. However, these imitations should not detract from our 'proof of concept' pilot study, although a larger trial of DWI screening for HCC is required.…”

“…Therefore, it is possible that both US and MRI may have missed tumours that remain undetected in our patients. These HCC's, however, are likely to be small and slow growing given that the doubling time of tumours is related to the level of differentiation which varies between 138 days to 32 days for Edmonson grade 1 and grade 3 tumours, respectively . It was reassuring that no patient was found to have developed a new tumour in a follow‐up period of at least 6 months.…”