Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer.

BACKGROUND: Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. METHODS: We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. RESULTS: Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. CONCLUSION: This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.

Comparison of various reconstructions derived from dual-energy CT immediately after endovascular treatment of acute ischemic stroke in predicting hemorrhage.

OBJECTIVES: Predicting 24-h hemorrhage immediately after endovascular treatment (EVT) of ischemic stroke is important but difficult for clinicians. We thus aimed to identify better image markers in predicting hemorrhage from different reconstructions derived from dual-energy CT. METHODS: We reviewed our prospectively collected database for anterior circulation ischemic stroke patients who received EVT and analyzed patients who underwent dual-energy CT immediately after EVT. Parenchymal hyperdensities were assessed on non-contrast CT and virtual non-contrast (VNC) which was constructed from dual-energy CT, respectively. Metallic hyperdensity sign was defined when a maximum density > 90 Hounsfield units was identified within the nonpetechial intracerebral hyperdense lesion in the basal ganglia on non-contrast CT. RESULTS: A total of 147 patients were included. Hemorrhagic transformation (HT) was identified in 81 (55.1%) patients, and parenchymal hemorrhage (PH) in 35 (23.8%) patients. The rate of HT at 24 h was higher in patients with parenchymal hyperdensities on non-contrast CT or VNC or with metallic hyperdensity sign than those without (72.4% vs 11.9%, p < 0.001; 82.0% vs 41.2%, p < 0.001; 100.0% vs 44.5%, p < 0.001). Parenchymal hyperdensities on non-contrast CT had a higher accuracy in predicting HT than those on VNC (76.9% vs 66.7%). Metallic hyperdensity sign on non-contrast CT also had a higher accuracy in predicting PH than parenchymal hyperdensities on VNC (88.4% vs 69.4%). CONCLUSIONS: Image markers on non-contrast CT (parenchymal hyperdensities and metallic hyperdensity sign) performed immediately post-EVT of ischemic stroke might be not inferior to dual-energy CT (parenchymal hyperdensities) to predict follow-up hemorrhage. KEY POINTS: • Image markers (parenchymal hyperdensities and metallic hyperdensity sign) on NCCT performed immediately post-EVT of ischemic stroke can predict follow-up hemorrhage. • Metallic hyperdensity sign on NCCT can accurately predict parenchymal hemorrhage. • Parenchymal hyperdensities on NCCT can accurately predict hemorrhagic transformation.

Association of maximal systolic blood pressure with poor outcome in patients with hyperattenuated lesions on immediate NCCT after mechanical thrombectomy.

BACKGROUND AND PURPOSE: This study aimed to investigate the relationship between blood pressure (BP) management and clinical outcome in patients with hyperattenuated lesions on non-contrast CT (NCCT) immediately after mechanical thrombectomy (MT). METHODS: We retrospectively reviewed our prospectively collected cohort for consecutive patients with acute ischemic stroke (AIS) who received MT between October 2013 and July 2018. Hourly systolic BP (SBP) and diastolic BP (DBP) values were recorded for 24 hours following MT, and then maximum SBP (SBPmax) and DBP (DBPmax) values were identified. Poor outcome was defined as 3-month modified Rankin score (mRS) 3-6 and parenchymal hemorrhage (PH) was defined according to the European Cooperative Acute Stroke Study (ECASS) II trial. Associations of BP parameters with poor outcome and PH were determined using binary logistic regression models. Receiver operating characteristics (ROC) curve analysis was used to determine the predictive value of BP. RESULTS: Initially 262 patients with AIS who received MT were reviewed and 148 patients with hyperattenuated lesions on immediate NCCT were enrolled in the final cohort for analysis. Binary logistic regression showed that every 10 mm Hg increase in SBPmax was independently associated with a poor outcome (OR 1.426; 95% CI 1.095 to 1.855; p=0.008) and PH (OR 1.025; 95% CI 1.005 to 1.480; p=0.044). SBP ≤140 mm Hg during the post-procedural 24-hour period was associated with lower odds of a poor outcome and PH compared with the other group. CONCLUSIONS: Control of maximal SBP within 24 hours might be related to a low rate of PH and poor outcome in patients with hyperattenuated lesions on immediate NCCT after intervention.

Longer Length of Delayed-Contrast Filling of Clot on 4-Dimensional Computed Tomographic Angiography Predicts Cardiogenic Embolism.

Background and Purpose- We hypothesized the length of delayed-contrast filling sign (DCFS) of intraarterial clot, indicating contrast medium penetration into the thrombus, was associated with stroke etiology. Methods- We retrospectively included patients with large vessel occlusion in anterior circulation who underwent computed tomographic perfusion within 24 hours poststroke onset. We defined DCFS as contrast medium diffusion through the thrombi after the arterial peak phase on 4-dimensional computed tomographic angiography derived from computed tomographic perfusion. We measured the length of DCFS and investigated its value for predicting the stroke etiology. Results- Three hundred twenty-one patients were analyzed, and their stroke etiologies included cardiogenic embolism (CE, n=167), large artery atherosclerosis (n=64), other etiology group (n=4), and undetermined etiology (n=86). CE patients had longer length of DCFS than non-CE patients (2.3 versus 0.5 mm; P<0.001). The optimal cutoff value of DCFS length for predicting CE was 1.5 mm. The sensitivity, specificity, positive predictive value, and negative predictive value of a length of DCFS >1.5 mm for predicting CE were 83.2%, 70.8%, 75.5%, and 79.6%. Conclusions- Longer length of DCFS was associated with CE in patients with large vessel occlusion in anterior circulation, which may provide stroke etiology information.

Pseudo-Occlusion of the Internal Carotid Artery Predicts Poor Outcome After Reperfusion Therapy.

BACKGROUND AND PURPOSE: This study aimed to evaluate the occurrence rate of the internal carotid artery pseudo-occlusion (ICA-PO) on 4-dimensional-computed tomography angiography and to investigate its relationship with clinical outcome after reperfusion therapy. METHODS: In this case-control study, we retrospectively reviewed our prospectively collected database for consecutive acute ischemic stroke patients who received reperfusion therapy between June 2009 and February 2017. ICA-PO was defined when the arterial segment was not opacified on peak arterial phase yet was subsequently patent after artery peak phase on 4-dimensional-computed tomography angiography. Poor outcome was defined as 3-month modified Rankin Scale of 4 to 6. Binary logistic regression was used to investigate the relationship of ICA-PO with poor outcome and the rate of reperfusion, respectively. RESULTS: A total of 143 patients with isolated middle cerebral artery occlusion were included and 30 (21.0%) had ICA-PO. Patients with ICA-PO were more likely to have poor outcome (80.0% versus 37.2%; P<0.001) and a lower rate of reperfusion (45.8% versus 69.0%; P=0.033) than those without. Binary logistic regression revealed that ICA-PO was independently associated with poor outcome (odds ratio, 7.957; 95% confidence interval, 1.655-34.869; P=0.009) and reperfusion at 24 hours (odds ratio, 0.150; 95% confidence interval, 0.045-0.500; P=0.002) after adjustment. Among patients with no reperfusion, all ICA-PO patients obtained poor outcome, whereas only 45.2% non-PO patients underwent poor outcome (P=0.001). CONCLUSIONS: Four dimensional-computed tomography angiography is a useful noninvasive technique to identify ICA-PO. Patients with ICA-PO are prone to undergo poor outcome from reperfusion therapy, especially when reperfusion is not achieved.

Severe Blood-Brain Barrier Disruption in Cardioembolic Stroke.

BACKGROUND: Previous studies demonstrated that cardioembolism (CE) was prone to develop hemorrhagic transformation (HT), whereas hyper-permeability of blood-brain barrier (BBB) might be one reason for the development of HT. We, thus, aimed to investigate whether the BBB permeability (BBBP) was higher in CE stroke than other stroke subtypes in acute ischemic stroke (AIS) patients. METHODS: This study was a retrospective review of prospectively collected clinical and imaging database of AIS patients who underwent CT perfusion. Hypoperfusion was defined as Tmax >6 s. The average relative permeability-surface area product (rPS), reflecting the BBBP, was calculated within the hypoperfusion region (rPShypo). CE was diagnosed according to the international Trial of Org 10172 in Acute Stroke Treatment criteria. Receiver operating characteristics (ROC) curve analysis was used to determine predictive value of rPShypo for CE. Logistic regression was used to identify independent predictors for CE. RESULTS: A total of 187 patients were included in the final analysis [median age, 73 (61-80) years; 75 (40.1%) females; median baseline National Institutes of Health Stroke Scale score, 12 (7-16)]. Median rPShypo was 65.5 (35.8-110.1)%. Ninety-seven (51.9%) patients were diagnosed as CE. ROC analysis revealed that the optimal rPShypo threshold for CE was 86.71%. The value of rPShypo and the rate of rPShypo>86.71% were significantly higher in patients with CE than other stroke subtypes (p < 0.05), after adjusting for the potential confounds. CONCLUSION: The extent of BBB disruption is more severe in CE stroke than other stroke subtypes during the hyperacute stage.

Reperfusion facilitates reversible disruption of the human blood-brain barrier following acute ischaemic stroke.

OBJECTIVES: We aimed to detect early changes of the blood-brain barrier permeability (BBBP) in acute ischaemic stroke (AIS), with or without reperfusion, and find out whether BBBP can predict clinical outcomes. METHODS: Consecutive AIS patients imaged with computed tomographic perfusion (CTP) before and 24 h after treatment were included. The relative permeability-surface area product (rPS) was calculated within the hypoperfused region (rPShypo-i), non-hypoperfused region of ischaemic hemisphere (rPSnonhypo-i) and their contralateral mirror regions (rPShypo-c and rPSnonhypo-c). The changes of rPS were analysed using analysis of variance (ANOVA) with repeated measures. Logistic regression was used to identify independent predictors of unfavourable outcome. RESULTS: Fifty-six patients were included in the analysis, median age was 76 (IQR 62-81) years and 28 (50%) were female. From baseline to 24 h after treatment, rPShypo-i, rPSnonhypo-i and rPShypo-c all decreased significantly. The decreases in rPShypo-i and rPShypo-c were larger in the reperfusion group than non-reperfusion group. The rPShypo-i at follow-up was a predictor for unfavourable outcome (OR 1.131; 95% CI 1.018-1.256; P = 0.022). CONCLUSION: Early disruption of BBB in AIS is reversible, particularly when greater reperfusion is achieved. Elevated BBBP at 24 h after treatment, not the pretreatment BBBP, predicts unfavourable outcome. KEY POINTS: • Early disruption of blood-brain barrier (BBB) in stroke is reversible after treatment. • The reversibility of BBB permeability is associated with reperfusion. • Unfavourable outcome is associated with BBB permeability at 24 h after treatment. • Contralateral non-ischaemic hemisphere is not 'normal' during an acute stroke.

Absent Filling of Ipsilateral Superficial Middle Cerebral Vein Is Associated With Poor Outcome After Reperfusion Therapy.

BACKGROUND AND PURPOSE: Our aim was to study the effect of drainage of cortical veins, including the superficial middle cerebral vein (SMCV), vein of Trolard, and vein of Labbé on neurological outcomes after reperfusion therapy. METHODS: Consecutive ischemic stroke patients who underwent pretreatment computed tomographic perfusion and 24-hour computed tomographic perfusion or magnetic resonance perfusion after intravenous thrombolysis were included. We defined "absent filling of ipsilateral cortical vein" (eg, SMCV-) as no contrast filling of the vein across the whole venous phase on 4-dimensional computed tomographic angiography in the ischemic hemisphere. RESULTS: Of 228 patients, SMCV-, vein of Trolard- and vein of Labbé- were observed in 50 (21.9%), 27 (11.8%), and 32 (14.0%) patients, respectively. Only SMCV- independently predicted poor outcome (3-month modified Rankin Scale score of >2; odds ratio, 2.710; P=0.040). No difference was found in reperfusion rate after treatment between patients with and without SMCV- (P>0.05). In patients achieving major reperfusion (≥80%), there was no difference in 24-hour infarct volume, or rate of poor outcome between patients with and without SMCV- (P>0.05). However, in those without major reperfusion, patients with SMCV- had larger 24-hour infarct volume (P=0.011), higher rate of poor outcome (P=0.012), and death (P=0.032) compared with those with SMCV filling. SMCV- was significantly associated with brain edema at 24 hours (P=0.037), which, in turn, was associated with poor 3-month outcome (P=0.002). CONCLUSIONS: Lack of SMCV filling contributed to poor outcome after thrombolysis, especially when reperfusion was not achieved. The main deleterious effect of poor venous filling appears related to the development of brain edema.

[Diagnostic value of dual energy CT for lymph node metastasis in patients with non-small cell lung cancer].

OBJECTIVE: To assess the diagnostic value of dual energy CT for lymph node metastasis in patients with non-small cell lung cancer (NSCLC). METHODS: Forty NSCLC patients, including 15 cases of squamous cell carcinoma and 25 cases of adenocarcinoma, underwent dual energy CT examination in pre-contrast and venous phase contrast scans, then the CT attenuation value of the lung cancer lesions and 85 mediastinal enlarged lymph nodes (the short diameter ≥ 5 mm, 53 metastatic and 32 non-metastatic) were measured at different energy levels (40-190 keV, spacing 10 keV) in venous phase contrast. CT spectral curves of the lung cancer lesions, hilus pulmonis and mediastinal enlarged lymph nodes were produced automatically, through comparing their CT spectral curves slope to judge whether or not the lymph nodes were metastatic. Receiver operating characteristic (ROC) curve was used to evaluate the efficiency of CT spectral curve in diagnosis of lymph node metastasis. RESULTS: The CT spectral curves slopes of the lung cancer, metastatic lymph nodes and non-metastatic lymph nodes were 1.10±0.11, 1.08±0.07 and 1.54±0.17, respectively. There was no significant difference in curve slope between metastatic lymph nodes and lung cancer (t=-1.32,P>0.05); while there was significant difference between non-metastatic lymph nodes and lung cancer (t=-2.58,P<0.05). The CT spectral curve slope ratios of metastatic and non-metastatic lymph nodes to lung cancer were 0.98±0.05 and 1.40±0.12, respectively (t=-2.86,P<0.05). ROC curve showed that taking CT spectral curve slope ratio of 1.15 as cut-off value for the diagnosis of metastatic lymph nodes, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 81.1%, 87.5%, 91.5%, 73.7% and 83.5%, respectively. CONCLUSIONS: Dual energy CT is of value in improving the diagnostic accuracy of lymph node metastasis in NSCLC patients before treatment.

Defining Core and Penumbra in Ischemic Stroke: A Voxel- and Volume-Based Analysis of Whole Brain CT Perfusion.

Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden's Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time ≥ 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF ≤ 30% within delay time ≥ 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time ≥ 3 s and rCBF ≤ 30% within delay time ≥ 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy.

Unfavorable neurological outcome in diabetic patients with acute ischemic stroke is associated with incomplete recanalization after intravenous thrombolysis.

OBJECTIVE: To assess the impact of diabetes on neurological outcome and recanalization in acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: Clinical data of 419 consecutive patients with AIS who received IVT between June 2009 and April 2014. Based on the medical history and new diagnosis, the patients were divided into groups with and without diabetes. Neurological outcomes at 24 h, 7 days and 3 months after IVT were evaluated. Favorable outcome was defined as National Institutes of Health Stroke Scale (NIHSS) score decrease ≥4 points from baseline or 0 at 24 h, NIHSS decrease ≥8 points or 0 at day 7, or modified Rankin scale ≤1 at 3 months after IVT. Recanalization on non-invasive imaging was evaluated in patients with large vessel occlusion (LVO) according to thrombolysis in myocardial infarction grades. RESULTS: Among 419 patients, 98 (23.4%) had diabetes. Multivariable analyses showed that comorbidity of diabetes was an independent predictor of unfavorable outcome at 24 h (OR=0.534, 95% CI 0.316 to 0.903, p=0.019), at day 7 (OR=0.382, 95% CI 0.220 to 0.665, p=0.001), and at 3 months (OR=0.464, 95% CI 0.266 to 0.808, p=0.007). In patients with LVO, diabetes was an independent predictor of incomplete recanalization 24 h after IVT (OR=0.268, 95% CI 0.075 to 0.955, p=0.042). CONCLUSIONS: Diabetic patients with AIS had unfavorable neurological outcome, potentially linked to incomplete recanalization after IVT.

Assessment of liver fibrosis in the early stages with perfusion CT.

OBJECTIVES: This work aims to assess the feasibility of perfusion CT in diagnosis of liver fibrosis in the early stage. MATERIALS AND METHODS: Solutions of carbon tetrachloride (CCL4) were injected into the peritoneum of 45 rabbits to establish rabbit models of liver fibrosis. Perfusion CT were performed at 4-, 8-, 12- and 16- week after injection. The parametric perfusion indices of blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal venous perfusion (PVP), and hepatic perfusion index (HPI) on perfusion maps were measured. Liver samples were scored as F0, F1, F2, F3, F4 for fibrosis. RESULTS: In 50 rabbits, 23 rabbits survived. Of these survival rabbits, 5 rabbits were histopathologically scored as F0, 7 rabbits were F1, 8 rabbits were F2, and 3 rabbits were F3. For relatively small number of F3, multiple comparisons were made for F0 vs. F1, F1 vs. F2 and F0 vs. F2. A statistically significant difference was observed in PVP, BV, BF, ALP and HPI between F1 vs. F2 and F0 vs. F2, whereas a significant statistical difference was only achieved in PVP between F0 vs. F1. In the early stage of liver fibrosis PVP decreased with the progression of liver fibrosis, whereas HPI, ALP and BF increased with the progression of liver fibrosis. BV had no marked change. CONCLUSIONS: Perfusion CT is feasible in diagnosis of early stage of liver fibrosis. PVP appears to be the most promising parametric perfusion index.

[Thresholds of CT perfusion in predicting ischemic penumbra and infarct core in patients with acute ischemic stroke].

OBJECTIVE: To determine the optimal parameters and their thresholds on CT perfusion (CTP) to predict the penumbra and core in patients with acute ischemic stroke. METHODS: The data of 39 thrombolytic candidates with acute cerebral anterior-circulation ischemic stroke admitted in the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to October 2013 were retrospectively reviewed. Patients all underwent CTP at admission and CTP or magnetic resonance perfusion (MRP) 24 h after thrombolysis. Patients were classified as non-reperfusion group (to define the threshold of penumbra, n=10) and reperfusion group (to define the threshold of infarct core, n=21) by reperfusion status. According to the baseline CTP and 24 h imaging, the volumes of threshold-based hypoperfusion lesions and final infarction were calculated. Paired t test, correlation analysis and Bland-Altman plot were performed to assess the optimal thresholds for predicting the penumbra and infarct core. RESULTS: In non-reperfusion group, the best agreement was found between final infarct volume and delay time>3 s (bias 3.3 ml, 95% limits of agreement:-41.7 to 48.3 ml, r=0.933, P<0.001), while in reperfusion group, the best agreement was noted between final infarct volume and rCBF<30% (bias -2.2 ml, 95% limits of agreement:-25.6 to 21.2 ml; r=0.923, P<0.001). CONCLUSION: Delay time>3 s and rCBF<30% are the optimal thresholds for predicting the penumbra and infarct core on CTP, respectively. These thresholds may be of help to estimate the mismatch status and select eligible patients for thrombolysis.

[Dynamic CT angiography in evaluation of collateral flow and outcome of acute ischemic stroke patients after intravenous thrombolysis].

OBJECTIVE: To evaluate the collateral flow of patients with acute ischemic stroke by dynamic CT angiography (CTA) and to analyze the relationship between collateral flow and outcome after intravenous thrombolysis. METHODS: We retrospectively analyzed CT perfusion (CTP) imaging of 22 acute ischemic stroke patients with middle cerebral artery (MCA) or internal carotid artery (ICA) occlusion undergoing intravenous thrombolysis, and reconstructed the images for dynamic CTA in the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to October 2013. The total extent and flow speed of collateral flow based on dynamic CTA images of these patients were evaluated. The scores of National Institute of Health stroke scale (NIHSS) in different collateral flows were compared with repeated measuring. The nonparametric Spearman's rank correlation was used to assess the relationship between collateral flow and modified Rankin scale (mRS) at 3 months after thrombolytic therapy. RESULTS: Compared with the poor collateral flow group, patients with good collateral flow had lower NIHSS at 1 month after thrombolysis (4.7±5.0 vs 25.1±15.1, P=0.001) and higher reperfusion percentage (69%±32% vs 23%±54%, P=0.044). The total condition score of collateral flow was positively correlated with mRS at 3 months after treatment (r=0.450, P=0.001). CONCLUSION: Acute ischemic stroke patients with good collateral flow after intravenous thrombolysis have a better outcome. The dynamic CTA can be used to evaluate the collateral flow and to predict clinical outcomes in patients with acute ischemic stroke after thrombolysis therapy.

[Histopathological changes in rat transplanted hepatoma after lipiodol transarterial embolization].

OBJECTIVE: To study the histopathological effect of hepatic arterial infusion of lipiodol on transplanted hepatoma in rats. METHODS: Fourty-one rats bearing Walker-256 transplanted hepatoma were randomly divided into embolization group (n = 35, divided in 5 subgroups, with 7 rats in each) and control group (n = 6). Lipiodol (0.5 ml/kg)emulsified with 0.2 - 0.3 ml of 76% urografin (v:v = 1:1) was infused via gastroduodenal artery into hepatic artery in embolization group. Rats in the control group were given via the same route urografin only. Histopathological changes of the treated tumors were examined by light and transmission electron microscopy. RESULTS: In the control rats treated with urografin alone, the average tumor size increased 2.8 fold on day 3, while that in the lipiodol treated rats increased 1.7 fold (P < 0.01). Compared with the control group, on day 3, 5, 10 after embolization treatment, tumor necrosis was more extensive (P < 0.01). In one of the treated rats, the tumor was completely necrotic on day 10. Inflammatory reaction was marked in the early post-embolic period, but it was replaced by fibrous tissue encapsulation. From day 1 on, in 17 of the 18 treated rats, apoptotic cells, identified by typical morphology under light and electronic microscopes, were observed, mainly in the tumor periphery. CONCLUSION: In addition to cellular necrosis, apoptosis may be another important mechanism leading to cell death in hepatoma treated with transarterial embolization.