Metabolic alterations in a rat model of hepatic ischaemia reperfusion injury: In vivo hyperpolarized 13 C MRS and metabolic imaging.

BACKGROUND & AIMS: Despite a number of studies addressing the pathophysiology of hepatic IRI, a gold standard test for early diagnosis and evaluation of IRI remains elusive. This study investigated the metabolic alterations in a rat model of hepatic IRI using the in vivo hyperpolarized ¹³C MRS and metabolic imaging. METHODS: Hyperpolarized 13 C MRS with IVIM-DWI was performed on the liver of 7 sham-operated control rats and 7 rats before and after hepatic IRI. RESULTS: The hepatic IRI-induced rats showed significantly higher ratios of [1-13 C] alanine/pyruvate, [1-13 C] alanine/tC, [1-13 C] lactate/pyruvate and [1-13 C] lactate/tC compared with both sham-operated controls and rats before IRI, whereas [1-13 C] pyruvate/tC ratio was decreased in IRI-induced rats. In IVIM-DWI study, apparent diffusion coefficient (ADC), f and D values in rats after hepatic IRI were significantly lower than those of rats before IRI and sham-operated controls. The levels of [1-13 C] alanine and [1-13 C] lactate were negatively correlated with ADC, f and D values, whereas the level of [1-13 C] pyruvate was positively correlated with these values. CONCLUSIONS: The levels of [1-13 C] alanine, [1-13 C] lactate and [1-13 C] pyruvate in conjunction with IVIM-DWI will be helpful to evaluate the hepatic IRI as well as these findings can be useful in understanding the biochemical mechanism associated with hepatic damage.

Combined Therapy of Transcatheter Arterial Chemoembolization and Radiofrequency Ablation versus Surgical Resection for Single 2-3 cm Hepatocellular Carcinoma: A Propensity-Score Matching Analysis.

PURPOSE: To compare therapeutic outcomes of radiofrequency (RF) ablation combined with transcatheter arterial chemoembolization vs surgical resection (SR) for single 2-3 cm hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy patients underwent combined chemoembolization/RF ablation therapy and 84 underwent SR. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), disease-free survival (DFS), and overall survival (OS) rates, as well as major complications and duration of hospital stay, were compared between groups before and after propensity-score matching. RESULTS: LTP and IDR had developed in 9 (12.9%) and 24 (34.3%) patients in the combined treatment group and in 7 (8.3%) and 24 (28.6%) patients in the SR group (P = .262 and P = .252, respectively). The 1-, 3-, 4-, and 5-year DFS rates were similar between groups (82.6%, 53.2%, 53.2%, and 37.6%, respectively, vs 84.5%, 63.6%, 59.2%, and 52.1%, respectively; P = .278), and 1-, 3-, 4-, and 5-year OS rates were also comparable (94.2%, 81.2%, 74.1%, and 59.4%, respectively, vs 95.2%, 86.3%, 84.0%, and 80.3%, respectively; P = .081). After matching (n = 98), LTP, IDR, DFS, and OS rates were still similar (P = .725, P = .826, P = .484, and P = .578, respectively). Major complication rate was not significantly different (2.9% vs. 6.0%; P = .596); however, after matching, major complication rate was higher in SR group (2.0% vs. 6.1%; P < .001). Hospital stays were significantly longer in the SR group (16.6 ± 6.7 d vs 8.5 ± 4.1 d; P < .001). CONCLUSIONS: Before and after matching, there were no significant differences in long-term therapeutic outcomes between combined chemoembolization/RF ablation and SR groups. Therefore, combined chemoembolization/RF ablation therapy may be an alternative treatment for single 2-3 cm HCCs.

Intravoxel incoherent motion diffusion-weighted imaging for monitoring chemotherapeutic efficacy in gastric cancer.

AIM: To assess intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model. METHODS: IVIM-DWI was performed with 12 b-values (0-800 s/mm(2)) in 25 human gastric cancer-bearing nude mice at baseline (day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups (n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calcium folinate treatment. Together with tumor volumes (TV), the apparent diffusion coefficient (ADC) and IVIM parameters [true water molecular diffusion coefficient (D), perfusion fraction (f) and pseudo-related diffusion coefficient (D(*))] were measured. The differences in those parameters from baseline to each measurement (ΔTV%, ΔADC%, ΔD%, Δf% and ΔD(*)%) were calculated. After image acquisition, tumor necrosis, microvessel density (MVD) and cellular apoptosis were evaluated by hematoxylin-eosin (HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman's correlation coefficient analysis were performed. RESULTS: The observed relative volume increase (ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5 (ΔTVtreatment% = 19.63% ± 3.01% and ΔTVcontrol% = 83.60% ± 14.87%, P = 0.008) and day 7 (ΔTVtreatment% = 29.07% ± 10.01% and ΔTVcontrol% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group (ΔADC%treatment, median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group (ΔADC%control, median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7 (P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group (ΔD%treatment, median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group (ΔD%control, median -0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5 (P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up (median, -34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016; -50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008; -49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and -46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points (median, -32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008; -44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008; -59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and -47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis (r s = 0.720, P < 0.001; r s = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D (r s = 0.626, P = 0.001; r s = 0.542, P = 0.005, respectively). Perfusion-related parameters (f and D(*)) were positively correlated to MVD (r s = 0.618, P = 0.001; r s = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor (r s = -0.550, P = 0.004; r s = -0.692, P < 0.001, respectively). CONCLUSION: IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.