Relative Initial Weight Is Associated with Improved Survival without Altering Tumor Latency in a Translational Rat Model of Diethylnitrosamine-Induced Hepatocellular Carcinoma and Transarterial Embolization.
ABSTRACT: PURPOSE:To test the hypotheses that (i) heavier rats demonstrate improved survival with diminished fibrosis in a diethylnitrosamine (DEN)-induced model of hepatocellular carcinoma (HCC) and (ii) transarterial embolization via femoral artery access decreases procedure times versus carotid access. MATERIALS AND METHODS:One hundred thirty-eight male Wistar rats ingested 0.01% DEN in water ad libitum for 12 weeks. T2-weighted magnetic resonance imaging was used for tumor surveillance. Rats underwent selective embolization of ? 5 mm tumors via carotid or femoral artery catheterization under fluoroscopic guidance. Rats were retrospectively categorized into 3 groups by initial weight (< 300, 300-400, > 400 g) for analyses of survival, tumor latency, and fibrosis. Access site was compared relative to procedural success, mortality, and time. RESULTS:No significant differences in tumor latency were related to weight group (P = .310). Rats weighing < 300 g had shorter survival than both heavier groups (mean, 88 vs 108 d; P < .0001), and more severe fibrosis (< 300 g median, 4.0; 300-400 g median, 1.5; > 400 g median, 1.0; P = .015). No significant difference was found in periprocedural mortality based on access site; however, procedure times were shorter via femoral approach (mean, 71 ± 23 vs 127 ± 24 min; P < .0001). CONCLUSIONS:Greater initial body weight resulted in improved survival without prolonged tumor latency for rats with DEN-induced HCCs and was associated with less severe fibrosis. A femoral approach for embolization resulted in decreased procedure time. These modifications provide a translational animal model of HCC and transarterial embolization that may be suited for short-term survival studies.
Project description:Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide and the majority of HCC patients occur with a background of hepatic fibrosis and cirrhosis. We have previously reported the hepatoprotective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in a chronic ethanol-treated rat model. Here, we assessed the anti-fibrotic and anti-carcinogenic effects of SMSP on diethylnitrosamine (DEN)-treated rats. Wistar rats were intraperitoneally injected with DEN once a week for 12 or 16 weeks with or without SMSP administration (0.1 and 1 g/kg). SMSP administration significantly attenuated tumor foci formation and proliferation in the livers of the rats treated with DEN for 16 weeks. SMSP administration also inhibited hepatic fibrosis by decreasing the levels of collagen fiber and the expression of pro-collagen I and alpha-smooth muscle actin (?-SMA). Moreover, SMSP supplementation improved the major parameters of fibrosis such as transforming growth factor-? (TGF-?), connective tissue growth factor (CTGF), tumor necrosis factor-alpha (TNF-?), plasminogen activator inhibitor-1 (PAI-1), and collagen type I (Col1A1) in the livers from the rats treated with DEN for 16 weeks. As s possible mechanisms, we investigated the effects of SMSP on the TGF-? and signal transducer and activator of transcription 3 (STAT3)-mediated signaling cascades, which are known to promote hepatic fibrosis. We found that SMSP treatment inhibited the activation of TGF-? and the phosphorylation of STAT3 pathway in DEN-treated rats. Moreover, SMSP administration suppressed the expressions of the target genes of TGF-? and STAT3 induced by DEN treatment. Our findings provide experimental evidences that SMSP administration has inhibitory effects of hepatic fibrosis and HCC induced by DEN in vivo and could be a promising strategy for the prevention or treatment of hepatic fibrosis and hepatocellular carcinogenesis.
Project description:Nontarget embolization during transarterial chemoembolization, although infrequent, can be a serious complication. The authors describe a case of nontarget gastric embolization to the stomach after transarterial chemoembolization and describe the published incidence of nontarget embolization to various organs, its diagnosis, treatment, and possible outcomes.
Project description:Hepatic fibrosis and cirrhosis are a growing global health problem with increasing mortality rates. Early diagnosis and staging of hepatic fibrosis represent a major challenge. Currently liver biopsy is the gold standard for fibrosis assessment; however, biopsy requires an invasive procedure and is prone to sampling error and reader variability. In the current study we investigate using quantitative analysis of computer-extracted features of B-mode ultrasound as a non-invasive tool to characterize hepatic fibrosis. Twenty-two rats were administered diethylnitrosamine (DEN) orally for 12 weeks to induce hepatic fibrosis. Four control rats did not receive DEN. B-mode ultrasound scans sampling throughout the liver were acquired at baseline, 10, and 13 weeks. Computer extracted quantitative parameters representing brightness (echointensity, hepatorenal index) and variance (heterogeneity, anisotropy) of the liver were studied. DEN rats showed an increase in echointensity from 37.1 ± SD 7.8 to 53.5 ± 5.7 (10 w) to 57.5 ± 6.1 (13 w), while the control group remained unchanged at an average of 34.5 ± 4.5. The three other features studied increased similarly over time in the DEN group. Histologic analysis showed METAVIR fibrosis grades of F2-F4 in DEN rats and F0-F1 in controls. Increasing imaging parameters correlated with increasing METAVIR grades, and anisotropy showed the strongest correlation (ρ = 0.58). Sonographic parameters combined using multiparametric logistic regression were able to differentiate between clinically significant and insignificant fibrosis. Quantitative B-mode ultrasound imaging can be implemented in clinical settings as an accurate non-invasive tool for fibrosis assessment.
Project description:To compare the safety and efficacy of ultrasound guided percutaneous glue (N-butyl-2-cyanoacrylate) embolization with transarterial embolization in the management of iatrogenically injured arteries while performing paracentesis or thoracocentesis in patients with chronic liver disease.Hospital database was searched for cirrhotic patients having abdominal/thoracic wall haemorrhage following paracentesis/thoracocentesis procedure from January 2011 to June 2016. Doppler ultrasound and/or CT angiography were used to localize the site of haemorrhage and patients were treated by transarterial embolization or ultrasound-guided percutaneous glue embolization. Technical success was defined as cessation of haemorrhage as evidenced by angiography/Doppler ultrasound and clinical success was evaluated in terms of stabilization of the vital signs without the need for further transfusion or pressors, and survival. In both groups, the time to "imaging diagnosis of haemorrhage" and "successful embolization" with the outcome was analysed.23 cirrhotic patients had bleeding following a percutaneous procedure, 8 (Group 1) of them underwent transarterial embolization while 15 (Group 2) underwent ultrasound-guided percutaneous glue embolization. Mean time needed for embolization in Group 1 was 41?min while in Group 2 was 9?min (p < 0.001). Technical success was achieved in all but one case requiring repeat glue embolization. Initial clinical improvement was noted in all cases but the 30-day mortality owing to all causes was not significantly different between treatment groups.The study and its outcome suggest that ultrasound guided percutaneous glue embolization is a quick and effective treatment for iatrogenic haemorrhage following paracentesis/thoracocentesis in cirrhotic patients with comparable results to transarterial embolotherapy. Advances in knowledge: This study details an innovative technique of ultrasound guided percutaneous glue embolization of the iatrogenically injured vessel in the management of active extravasation and pseudoaneurysm developing after paracentesis/thoracocentesis in patients with cirrhosis.
Project description:Adrenal myelolipoma is a benign tumor of the adrenal cortex composed predominantly of fat and hematopoietic tissue. These lesions are usually asymptomatic, and most often incidentally detected on imaging. Uncommonly, they present with retroperitoneal hemorrhage, and these have been traditionally treated with emergent surgery. Although, transarterial embolization has been effectively and safely used in patients presenting with active hemorrhage from acute traumatic and nontraumatic causes, literature specifically pertaining to adrenal artery embolization is scant, perhaps due to smaller size and variability of adrenal arteries. With recent advances in endovascular techniques and imaging, there are emerging case reports and series of adrenal artery embolization in acute and nonacute settings. We report a case of spontaneous hemorrhage within an adrenal myelolipoma in a 43-year-old male patient, successfully treated with transarterial embolization, thereby avoiding major surgery. Our report adds to the growing body of literature pertaining to adrenal artery embolization.
Project description:Chronic liver inflammation progressively evokes fibrosis and cirrhosis resulting in compromised liver function, and often leading to cancer. Early diagnosis and staging of fibrosis is crucial because the five-year survival rate of early-stage liver cancer is high. This study investigates the progression of hepatic fibrosis induced in rats following ingestion of diethylnitrosamine (DEN). Changes in oxygen saturation and hemoglobin concentration resulting from chronic inflammation were assayed longitudinally during DEN ingestion by photoacoustic imaging (PAI). Accompanying liver tissue changes were monitored simultaneously by B-mode sonographic imaging. Oxygen saturation and hemoglobin levels in the liver increased over 5 weeks and peaked at 10 weeks before decreasing at 13 weeks of DEN ingestion. The oxygenation changes were accompanied by an increase in hepatic echogenicity and coarseness in the ultrasound image. Histology at 13 weeks confirmed the development of severe fibrosis and cirrhosis. The observed increase in PA signal representing enhanced blood oxygenation is likely an inflammatory physiological response to the dietary DEN insult that increases blood flow by the development of neovasculature to supply oxygen to a fibrotic liver during the progression of hepatic fibrosis. Assessment of oxygenation by PAI may play an important role in the future assessment of hepatic fibrosis.
Project description:A 74-year-old male presented with an intracranial hemorrhage caused by multiple dural arteriovenous fistulas (DAVFs) in the left transverse sinus and right sigmoid sinus. Four months previously, the patient underwent tongue cancer removal with lymph node dissection and ligation of the right internal jugular vein. Endovascular embolization (transvenous and transarterial embolization) resulted in the complete disappearance of the fistulas. Follow-up angiography revealed new arteriovenous shunts at the superior sagittal sinus and right transverse sinus, and we treated the patient with staged transarterial embolization. Finally, venous congestion almost completely resolved and the DAVFs disappeared without any sign of recurrence. This case speculates the concept of DAVF as an acquired lesion caused by intravenous hypertension and alerts clinicians to take precautions against ligation of the internal jugular vein during a cervical operation.
Project description:Studies on treatment modalities for primary hepatic neoplasms (PHN) in Canada are lacking. Our primary aim was to analyze the age-standardized incidence of hepatic resection, ablation, transplantation, and embolization for PHN between 2002 and 2013. Secondary aim was to evaluate temporal trends for these treatment modalities.National Canadian Cancer Registries were accessed for relevant epidemiological data. Age-standardized incidence of treatment ratios (SIRs) was calculated and comparisons were performed for Atlantic Canada, Ontario, the Prairies, and British Columbia.British Columbia recorded the highest SIRs for ablation (1.9; 95% CI 1.8-2.0), hepatic resection (1.2; 95% CI 1.1-1.3), and transarterial locoregional therapies (2.8; 95% CI 2.4-3.2). For hepatic resection, the lowest SIR was found in Atlantic Canada (0.7; 95% CI 0.6-0.9), while the Prairies recorded the lowest estimate for transarterial therapies (0.2; 95% CI 0.1-0.4). Liver transplantation had the highest SIR in Ontario (1.5; 95% CI 1.3-1.6) and the lowest SIR in British Columbia. No significant temporal changes in SIRs were observed for any of the treatments except for transarterial therapies.Treatment of PHN in Canada differs by geography. Variations might be due to differences in expertise or access to therapeutic modalities.
Project description:Transarterial access to dural arteriovenous fistulas (dAVFs) has been popularized by device improvements and novel embolic materials. However, this approach is limited in the cavernous sinus (CS) because of related complications and low cure rates. Although a transvenous approach, via ipsilateral inferior petrosal sinus (IPS), may be more suitable for CS-dAVFs, microcatheter delivery is occasionally impeded by ipsilateral IPS occlusion. Described herein is a microguidewire looping method to breach such occlusions, thus enabling access to CS lesions.A microcatheter is initially advanced into the IPS orifice, and a microguidewire is passed into the occluded IPS. Looping is easily achieved through the resistance met. With greater support of the guiding catheter, the microguidewire (still looped) is then advanced into the CS. When nearing the CS, the microcatheter is further reinforced, and it is navigated along the microguidewire into the CS.This technique was applied in 10 instances of CS-dAVF with ipsilateral IPS occlusion, enabling ipsilateral access to the CS. In eight cases (80%), microdevice advancement was successful, culminating in effective transvenous coil embolization. Clinical and radiologic outcomes in all patients were excellent, with no delayed post-procedural cranial palsies.This microguidewire looping technique enables safe and effective entry into the CS during transvenous coil embolization of CS-dAVFs with ipsilateral IPS occlusion.
Project description:BACKGROUND:Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide due to the lack of effective treatments. Chemoprevention in high-risk patients is a promising, alternative strategy. In this study, pioglitazone was investigated for its ability to prevent hepatocarcinogenesis in two rodent models of cirrhosis. METHODS:In the first model, male Wistar rats were given repeated, low-dose injections of diethylnitrosamine (DEN) to accurately recapitulate the progression of fibrosis to cirrhosis and HCC. In the second model, a single dose of DEN was administered to male C57Bl/6 pups at day fifteen followed by administration of a choline-deficient, L-amino acid defined, high-fat diet (CDAHFD) at week six for 24 weeks. Pioglitazone treatment started at the first signs of fibrosis in both models. RESULTS:Pioglitazone effectively reduced fibrosis progression and HCC development in both models. Gross tumor nodules were significantly reduced after pioglitazone treatment (7.4 ± 1.6 vs. 16.6 ± 2.6 in the rat DEN model and 5.86 ± 1.82 vs. 13.2 ± 1.25 in the mouse DEN+CDAHFD model). In both models, pioglitazone reduced the activation of mitogen-activated protein kinase (MAPK) and upregulated the hepato-protective AMP-activated protein kinase (AMPK) pathway via increasing circulating adiponectin production. CONCLUSION:Pioglitazone is an effective agent for chemoprevention in rodents and could be repurposed as a multi-targeted drug for delaying liver fibrosis and hepatocarcinogenesis.