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Aim: To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate (CA4P), among hepatocellular carcinomas (HCCs) and implanted rhabdomyosarcoma (R1) in the same rats by magnetic-resonance-imaging (MRI), microangiography and histopathology., Methods: Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images (T2WI/T1WI) on a 3.0T clinical MRI-scanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced (DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg (treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg (control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve (AUC30). In vivo MRI findings were verified by postmortem techniques., Results: On CE-T1WIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure (66%) in R1-tumors at 1 h ( P < 0.05), followed by further perfusion decrease at 12 h ( P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors (92.6%) than in HCCs (50.2%) ( P < 0.01); tumor vascularity heterogeneously scored +~+++ in HCCs but homogeneously scored ++ in R1-tumors., Conclusion: This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disrupting-agents.​., Competing Interests: Conflict-of-interest statement: The authors declare no potential conflicts of interest.

Aim: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones., Methods: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence (365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography (HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones (VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses (5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct (CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS)., Results: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10(-6) M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericin-glucuronide was detected., Conclusion: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.

Aim: To explore whether the antitumor effect of a vascular disrupting agent (VDA) would be enhanced by combining with an antiangiogenic agent, and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging (DW-MRI)., Methods: Thirty-seven rats with implanted liver tumors were randomized into the following three groups: (1) ZD6126, a kind of VDA; (2) ZDTHA, ZD6126 in combination with an antiangiogenic, thalidomide; and (3) control. Morphological DW-MRI were performed and quantified before, 4 h and 2 d after treatment. The apparent diffusion coefficient (ADC) values were calculated separately for low b values (ADC(low)), high b values (ADC(high)) and all b values (ADC(all)). The tissue perfusion contribution, ADC(perf), was calculated as ADC(low)-ADC(high). Imaging findings were finally verified by histopathology., Results: The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis. In addition to delaying tumor growth, ZDTHA caused tumor necrosis in an additive manner, which was verified by HE staining. Although both ADC(high) and ADC(all) in the ZD6126 and ZDTHA groups were significantly higher compared to those in the control group on day 2, the entire tumor ADC(high) of ZDTHA was even higher than that of ZD6126, but the significant difference was not observed for ADC(all) between ZDTHA and ZD6126. This indicated that the perfusion insensitive ADC(high) values calculated from high b value images performed significantly better than ADC(all) for the monitoring of tumor necrosis on day 2. The perfusion sensitive ADC(perf) derived from ADC(low) by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126, compared to the ADC(low) at 4 h. The ADC(perf) could provide valuable perfusion information from DW-MRI data., Conclusion: The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126 and thalidomide for solid tumors.

The concept of magnetic resonance perfusion-diffusion mismatch (PDM) provides a practical and approximate measure of the tissue at risk and has been increasingly applied for the evaluation of hyperacute and acute stroke in animals and patients. Recent studies demonstrated that PDM does not optimally define the ischemic penumbra; because early abnormality on diffusion-weighted imaging overestimates the infarct core by including part of the penumbra, and the abnormality on perfusion weighted imaging overestimates the penumbra by including regions of benign oligemia. To overcome these limitations, many efforts have been made to optimize conventional PDM. Various alternatives beyond the PDM concept are under investigation in order to better define the penumbra. The PDM theory has been applied in ischemic stroke for at least three purposes: to be used as a practical selection tool for stroke treatment; to test the hypothesis that patients with PDM pattern will benefit from treatment, while those without mismatch pattern will not; to be a surrogate measure for stroke outcome. The main patterns of PDM and its relation with clinical outcomes were also briefly reviewed. The conclusion was that patients with PDM documented more reperfusion, reduced infarct growth and better clinical outcomes compared to patients without PDM, but it was not yet clear that thrombolytic therapy is beneficial when patients were selected on PDM. Studies based on a larger cohort are currently under investigation to further validate the PDM hypothesis.

Aim: To evaluate spiral computed tomography (CT) including virtual gastroscopy for diagnosis of gastric carcinoma in comparison with upper gastrointestinal series (UGI), fiberoptic gastroscopy (FG) and histopathology., Methods: Sixty patients with histologically proven gastric carcinoma (54 advanced and 6 early) were included in this study. The results of spiral CT were compared with those of UGI and FG. Two observers blindly evaluated images of spiral CT and UGI and video recording of FG with consensus in terms of diagnostic confidence with a five-point scale. Sensitivities of lesion detection, Borrmann's classification of spiral CT, UGI and FG, as well as the accuracy of TNM staging of spiral CT were determined by comparing them to surgical and histological findings., Results: The lesion detection rate was 98 % (59/60), 95 % (57/60) and 98 % (59/60) for spiral CT, UGI and FG, respectively. There were no statistical differences in the detection sensitivity among the three techniques (P>0.05). For the sensitivity in Borrmann's classification, spiral CT was higher than that of UGI (P=0.025) and similar to that of FG (P>0.05). The accuracy of spiral CT in staging the gastric carcinoma was 76.7 %. Six cases of early gastric carcinoma were all detected by spiral CT as well as FG., Conclusion: Spiral CT is equivalent to UGI and FG in the detection of gastric carcinoma, and superior to UGI but similar to FG in the Borrmann's classification of advanced gastric carcinoma. Spiral CT is more valuable than FG in the staging of gastric carcinoma.