Chemoembolization-induced arterial damage: Evaluation of three different chemotherapeutic protocols using epirubicin and miriplatin.

AIM: We aimed to evaluate hepatic vascular changes following lipiodol-based transarterial chemoembolization of hepatocellular carcinoma using epirubicin (EPI), miriplatin (MPT) and miriplatin plus low-dose epirubicin (MPT+EPI). METHODS: A total of 185 arteries in 118 patients who underwent chemoembolization using EPI (67 arteries in 48 patients), MPT (64 arteries in 37 patients) and MPT+EPI (54 arteries in 33 patients) were retrospectively examined. The maximum dose limit of MPT was 140 mg and that of EPI was 50 and 20 mg for the EPI and MPT+EPI groups, respectively. Vascular changes and local recurrence were evaluated by subsequent angiography. Factors affecting arterial damage were analyzed using multivariate logistic regression analysis. RESULTS: More severe arterial damage was observed in the EPI group (88.1%) than in the MPT+EPI (72.2%) and the MPT (18.7%) groups (P = 0.044 and P < 0.001, respectively). EPI usage (hazard ratio [HR] = 12.8, P < 0.001), selective chemoembolization (HR = 5.4, P < 0.001) and MPT usage (HR = 0.28, P = 0.020) were significant predictors for arterial damage induction. The local recurrence rate was lower for the lesions exhibiting arterial occlusion after chemoembolization (39.4%) than for the lesions exhibiting no vascular attenuation (73.9%) or wall irregularity (75.8%) (P = 0.001 and P = 0.005, respectively). CONCLUSION: High-dose EPI, MPT, and low-dose EPI plus MPT usage in chemoembolization for hepatocellular carcinoma induced the greatest, the least, and intermediate vascular damages, respectively. Therapeutic occlusion of tumor feeder vessels is associated with lower local recurrence.

Clinical utility and limitations of tumor-feeder detection software for liver cancer embolization.

PURPOSE: To evaluate the clinical utility and limitations of a computer software program for detecting tumor feeders of hepatocellular carcinoma (HCC) during transarterial chemoembolization (TACE). MATERIALS AND METHODS: Forty-six patients with 59 HCC nodules underwent nonselective digital subtraction angiography (DSA) and C-arm computed tomography (CT) in the same hepatic artery. C-arm CT data sets were analyzed using the software to identify potential tumor feeders during each TACE session. For DSA analysis, 3 radiologists were independently assigned to identify tumor feeders using the DSA images in a separate session. The sensitivity of the 2 techniques in detecting tumor feeders was compared, with TACE findings as the reference standard. Factors affecting the failure of the software to detect tumor feeders were assessed by univariate and multivariate analyses. RESULTS: We detected 65 tumor feeders supplying 59 HCC nodules during TACE sessions. The sensitivity of the software to detect tumor feeders was significantly higher than that of the manual assessment using DSA (87.7% vs. 71.8%, P<0.001). Multivariate analysis showed that a tumor feeder diameter of <1.0mm (hazard ratio [HR], 56.3; P=0.003) and lipiodol accumulation adjacent to the tumor (HR, 11.4; P=0.044) were the significant predictors for failure to detect tumor feeders. CONCLUSION: The software analysis was superior to manual assessment with DSA in detecting tumor feeders during TACE for HCC. However, the capability of the software to detect tumor feeders was limited by vessel caliber and by prior lipiodol accumulation to the tumor.

Survival after C-arm CT-assisted chemoembolization of unresectable hepatocellular carcinoma.

PURPOSE: To compare patient survival after transarterial chemoembolization with and without intraprocedural C-arm computed tomography (CT) in patients with unresectable hepatocellular carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 130 patients with unresectable hepatocellular carcinoma who underwent lipiodol-based chemoembolization using a C-arm cone-beam system. We compared patients who underwent chemoembolization with angiography alone (69 patients; April 2005-July 2007) to those who underwent C-arm CT-assisted chemoembolization (61 patients; July 2007-April 2010). Overall and local progression-free survivals were compared using the Kaplan-Meier estimator with log-rank testing. Univariate and multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Overall survival rates of patients who underwent chemoembolization with and without C-arm CT assistance were 94% and 79%, 81% and 65%, and 71% and 44% at 1, 2, and 3 years, respectively. Local progression-free survival rates of these patients were 43% and 27%, 31% and 10%, and 26% and 5% at 1, 2, and 3 years, respectively. Patients receiving C-arm CT-assisted chemoembolization had significantly higher overall (P=0.005) and local progression-free (P=0.003) survival rates than those receiving chemoembolization with angiography alone. Multivariate analysis showed that C-arm CT assistance was an independent factor associated with longer overall survival (hazard ratio, 0.40; P=0.033) and local progression-free survival (hazard ratio, 0.25; P=0.003). CONCLUSION: C-arm CT usage in addition to angiography during transarterial chemoembolization prolongs survival in patients with unresectable hepatocellular carcinoma.

Methylglyoxal induces apoptosis through activation of p38 mitogen-activated protein kinase in rat mesangial cells.

BACKGROUND: The formation of methylglyoxal (MG), a highly reactive dicarbonyl compound, is accelerated through several pathways, including the glycation reaction under diabetic conditions, presumably contributing to tissue injury in diabetes. On the other hand, apoptotic cell death of glomerular cells has been suggested to play a role in the development of glomerulosclerosis in various types of glomerular injuries. We therefore examined whether MG was capable of inducing apoptosis in rat mesangial cells to address the possible mechanism by which hyperglycemia-related products accelerated pathologic changes in diabetic glomerulosclerosis. METHODS: Rat mesangial cells were incubated with 0 to 400 micromol/L MG, followed by the detection of apoptosis by both TUNEL method and electrophoretic analysis for DNA fragmentation. In addition, we investigated intracellular mechanisms mediating MG-induced apoptosis, focusing especially on the p38 mitogen-activated protein kinase (MAPK) pathway. RESULTS: MG induced apoptosis in rat mesangial cells in a dose-dependent manner and was accompanied by the activation of p38alpha isoform. Aminoguanidine and N-acetyl-l-cysteine inhibited the MG-induced p38 MAPK activation, as well as apoptosis in rat mesangial cells, suggesting the involvement of oxidative stress in these phenomena. SB203580, a specific inhibitor of p38 MAPK also suppressed the MG-induced apoptosis in rat mesangial cells. CONCLUSIONS: These results suggest a potential role for MG in glomerular injury through p38 MAPK activation under diabetic conditions and may serve as a novel insight into the therapeutic strategies for diabetic nephropathy.