Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND: Enhanced magnetic resonance imaging (MRI) is widely used in the diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC), but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment. Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival (PFS). AIM: To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images. METHODS: Delineate the regions of interest (ROI) in arterial phase, portal venous phase and delayed phase of enhanced MRI. After extracting the combinatorial features of ROI, the features are fused to obtain deep learning radiomics (DLR)_Sig. DeLong's test was used to evaluate the diagnostic performance of different typological features. K-M analysis was applied to assess PFS in different risk groups, and the discriminative ability of the model was evaluated using the C-index. RESULTS: Tumor diameter and diolame were independent factors influencing the prognosis of PFS. Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases (P < 0.05).In deep transfer learning (DTL) and DLR, significant differences were observed between the multi-phase and individual phases feature sets (P < 0.05). K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months, respectively, and the predicted probabilities of 6 months, 1 year and 2 years were 92%, 60%, 40% and 98%, 90%,73%, respectively. The C-index was 0.764, indicating relatively good consistency between the predicted and observed results. DTL and DLR have higher predictive value for 2-year PFS in nomogram. CONCLUSION: Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph, it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.

Comparative Study of Percutaneous Transhepatic Biliary Stent Placement with or without Iodine-125 Seeds for Treating Patients with Malignant Biliary Obstruction.

PURPOSE: To prospectively evaluate safety and efficacy of biliary stent placement with iodine-125 (125I) seeds in patients with malignant obstructive jaundice (MOJ). MATERIALS AND METHODS: From July 2011 to June 2014, 55 patients were enrolled (group A, 11 men and 17 women, mean age 70.93 y ± 8.58; group B, 14 men and 13 women, mean age 70.26 y ± 9.71). All patients were randomly assigned to placement of a biliary stent with 125I seeds (group A) or biliary stent only (group B). After stent placement, outcomes were measured regarding relief of MOJ. Clinical success rate, survival time, and safety were recorded. P < .05 was considered to indicate significant difference. RESULTS: Stents were successfully placed in all 55 patients. MOJ was relieved in all patients, and there were no significant differences in complications related to stent insertion between the 2 groups. Mean and median stent patency were 191 days ± 19.8 (95% confidence interval [CI], 152-230 d) and 179 days ± 191.4 (95% CI, 87-267 d) in group A and 88.3 days ± 16.3 (95% CI, 61-114 d) and 77 days ± 88.2 (95% CI, 65-86 d) in group B (P < .001, log-rank test). Mean and median survival time were 222.6 days ± 21.0 (95% CI, 181-263 d) and 241 days ± 18.2 (95% CI, 179-270 d) in group A and 139.1 days ± 14.5 (95% CI, 110-167 d) and 142 days ± 16.3 (95% CI, 83-177 d) in group B (P < .001, log-rank test). CONCLUSIONS: 125I seeds combined with biliary stent placement could significantly improve stent patency. The procedure seems to be safe and to extend survival compared with self-expandable biliary stent placement.

Effects of albendazole nanoparticles in mice with hepatic echinococosis: Portal vein cannulation versus intravenous administration.

To compare the ABZ and its metabolites concentration in cyst tissue of hepatic alveolar echinococcosis administered by different routes, forty male Wistar rats receiving albendazole nanoparticles from tail vein and portal vein were divided into two groups, the concentration of ABZ and its metabolites ABZSO, ABZSO2, in the cyst tissue, were analyzed by HPLC at 2, 4, 8, 24, 36 h after administration. The parent drug and its metabolites were detected in plasm and the cyst tissue after portal cannulation and intravenous administration. The last results were the concentration of ABZ in the portal cannulation group was higher than in the intravenous group at every time point (p < 0.05). Compared to the intravenous group, the portal cannulation administration of ABZ led to a lower plasm concentration of ABZ. The concentration of ABZ and the active ABZSO were significantly higher in the portal cannulation group than that of the intravenous group.

Novel albendazole-chitosan nanoparticles for intestinal absorption enhancement and hepatic targeting improvement in rats.

To improve the treatment of helminthiasis, filariasis, and colorectal cancer, albendazole-associated chitosan nanoparticles (ABZ-CS-NPs) were prepared using the emulsion crosslinking volatile technique with contained sodium tripolyphosphate as the crosslinking agent and Poloxamer 188 as the auxiliary solvent. The structural characteristics of the NPs were determined using X-ray diffraction to analyze the interaction between CS and the drug. The NPs were then evaluated in terms of their physicochemical characteristics, drug release behavior, in vivo pharmacokinetic parameters, and biodistribution in animal studies. ABZ-loaded NPs with a uniformly spherical particle sizes (157.8 ± 2.82 nm) showed efficient drug loading, encapsulated efficiency, and high physical stability. The drug release from ABZ-CS-NPs was extended over several periods. Kinetic models were then fitted to determine the release mechanisms. ABZ and its metabolite albendazole sulfoxide (ABZSX) were analyzed in rats with mebendazole as the internal standard using reversed-phase high-performance liquid chromatography. Compared with the ABZ suspension groups, the relative bioavailability values of ABZ and ABZSX were 146.05 and 222.15%, respectively. In addition, the plasma concentration versus time curve is consistent with that of the two compartment models in the plasma concentration versus time curve. The results indicate that the ABZ-loaded NPs are promising novel ABZ candidates for passive diffusion in the treatment of hydatid cysts in the liver via oral administration.

[Therapeutic effect of hepatic artery infusion with albendazole microspheres on hepatic alveolar echinococcosis in rats].

OBJECTIVE: To observe therapeutic effect of hepatic artery infusion of albendazole solid dispersion-chitosan microspheres on hepatic alveolar echinococcosis (HAE) in rats. METHODS: After the establishment of hepatic alveolar echinococcosis model, 30 rats were randomly divided into control group (A), blank microspheres group (B), and albendazole microspheres group (C) with 10 rats in each group 0.3 ml normal saline, 27mg/kg blank microspheres and 2.7 mg/kg albendazole solid dispersion-chitosan microspheres with 0.3 ml normal saline were injected through hepatic artery of rats in the groups of A, B and C, respectively. At 1 d, 3 d, 7 d, 14 d, and 42 d after injection, venous blood were collected, and white blood cells (WBC), aspartate aminotransferase (AST), and alanine aminotransferase(ALT) were evaluated. All the rats were sacrificed on 42 d after injection, and HAE pathological changes were observed. RESULTS: Transient elevation of white blood cells was observed in all groups at 1 d after infusion [Group A (86.11 +/- 19.14) x 10(9)/L, B (117.11 +/- 21.76) x 10(9)/L, C (118.11 +/- 24.52) x 10(9)/L], at 7d WBC fell to normal level [A (7.85 +/- 6.57)x10(9)/L, B (11.73 +/- 4.85) x 10(9)/L, C (8.49 +/- 136)x10(9)/L]. In groups B and C, AST, ALT reached their peaks on day 3 after infusion [B: AST (193.15 +/- 21.57) U/L, ALT (78.39 +/- 9.78) U/L; C: AST (189.91 +/- 14.06) U/L, ALT (88.43 +/- 9.23) U/L], and decreased to normal level at 14d after infusion [B: AST (109.31 +/- 15.48) U/L, ALT(47.855 +/- 9.49) U/L; C: AST(105.37 +/- 8.16) U/L, ALT (49.53 +/- 6.75) UL]. Histopathological examination at 42d after infusion showed that in groups A and B structure of the cysts was virtually normal, but in group C most cysts showed necrosis in germinal layer. CONCLUSION: Hepatic artery infusion with albendazole solid dispersion-chitosan microspheres shows certain therapeutic effect on hepatic alveolar echinococcosis in rats.