Weak stromal Caveolin-1 expression in colorectal liver metastases predicts poor prognosis after hepatectomy for liver-only colorectal metastases.

Loss of stromal Caveolin-1 (CAV1) expression is associated with poor prognosis in various cancers. We evaluated the prognostic value of CAV1 expression of both cancer cells and stromal cells in colorectal liver metastases (CRLM) in patients undergoing hepatectomy. In this retrospective study, 109 patients were enrolled. CAV1 expression was studied by immunohistochemistry. The staining was scored semiquantitatively as weak or strong. Disease-free survival (DFS) and overall survival (OS) were calculated using both Kaplan-Meier and multivariate Coxregression methods. Weak stromal CAV1 expression was associated with decreased DFS and OS in univariate and in multivariate analysis (HR 2.00; 95% CI, 1.24-3.22; P = 0.004, and HR 2.47; 95% CI, 1.28-4.76; P = 0.007, respectively). Cancer cell CAV1 expression was not associated with DFS and OS. Five-year DFS and OS rates were 13% and 43%, respectively, in patients with weak stromal CAV1 expression and 40% and 71%, respectively, in patients with strong stromal CAV1 expression. In this study, we indicate that weak stromal CAV1 expression in CRLM is an adverse prognostic factor in patients who undergo liver resection for liver-only colorectal metastases. We suggest validation of this finding in an independent cohort and consideration of risk stratification for post-hepatectomy adjuvant follow-up and therapy.

Transarterial embolization with sorafenib in animal livers: a pharmacokinetics study.

PURPOSE: To assess the safety and feasibility of the targeted delivery of the antiangiogenic drug sorafenib to the liver using transarterial chemoembolization methodology as a novel approach to hepatocellular carcinoma (HCC) therapy. MATERIALS AND METHODS: Seven healthy New Zealand white rabbits were used in the study. After placement of a catheter in the common hepatic artery, six rabbits were treated with chemoembolization of sorafenib in iodized oil (Lipiodol) (sorafenib dose 0.1 mg/kg), and one rabbit received Lipiodol only. Liquid chromatography tandem mass spectrometry was used to measure the concentration of sorafenib in the peripheral blood and liver tissue 24 hours and 72 hours after treatment. Histochemical staining of the liver sections and biochemical measurements were performed. RESULTS: The administration of sorafenib in Lipiodol emulsions by transarterial chemoembolization resulted in sorafenib concentrations of 794 ng/g ± 240 and 64 ng/g ± 15 in the liver tissue 24 hours and 72 hours after treatment. The average liver-to-serum ratios 24 hours and 72 hours after treatment were approximately 14 and 22. The histochemical staining of the liver tissue sections and aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase and total bilirubin concentrations indicated no significant liver damage. CONCLUSIONS: Transarterial chemoembolization with sorafenib in Lipiodol is an effective methodology for the localized delivery of this drug to the liver and has possible practical implications in therapeutic interventions for the treatment of hepatocellular carcinoma.

Video-assisted lung resection using radiofrequency ablation in a porcine model.

BACKGROUND: The aim of this study was to assess the feasibility, efficacy, and safety of video-assisted lingula resection using radiofrequency ablation (RFA) with internally cooled electrodes in a porcine model. MATERIALS AND METHODS: Six domestic pigs underwent RFA-assisted thoracoscopic lingulectomy. RFA was the only aerostatic and hemostatic method applied throughout the operation. After 30 d, the animals were sacrificed for the study of the macroscopic and microscopic effects of the technique. RESULTS: No signs of pneumothorax, blood loss, or infection were observed up to 1 mo postoperatively. There was no mortality either during or after surgery. The histopathology of the lung revealed three clearly demarcated zone lesions. CONCLUSIONS: Our study demonstrates that thoracoscopic lingulectomy using RFA energy is technically feasible. RFA energy is an effective and safe aerostatic and hemostatic method in the porcine model.

The expression of matrix metalloproteinases-2 and -9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters.

AIM: To investigate the expression of metalloproteinase (MMP) -2, MMP-9 and tissue inhibitor of MMP (TIMP) -2 in pancreatic ductal and ampullary carcinoma and to test the findings for correlation with angiogenesis and several clinicopathological parameters. PATIENTS AND METHODS: Paraffin sections from 32 pancreatic ductal adenocarcinomas and 17 ampullary carcinomas were assessed for the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemistry. Stromal and epithelial staining was evaluated separately. Moreover, sections stained immunohistochemically with anti-CD34 antibody were evaluated by image analysis for the quantification of microvessel density (MVD). RESULTS: In pancreatic ductal adenocarcinoma, lower levels of glandular TIMP-2 were found in poorly differentiated tumors, while high glandular TIMP-2 expression was significantly associated with better survival. The age of the patients and the degree of differentiation of the tumor were identified as independent prognostic parameters. No relation was found between the expression of MMPs, TIMP or angiogenesis and the parameters under consideration. In ampullary adenocarcinoma, strong expression of glandular MMP-2 was associated with higher MVD values. Moreover, lymph vessel invasion was associated with higher stromal TIMP-2. CONCLUSION: In pancreatic ductal adenocarcinoma, TIMP-2 may have a more crucial role in prognosis than MMP-2, MMP-9 or angiogenesis. In ampullary adenocarcinoma, MMP-2 expression correlated with MVD, supporting its postulated role in angiogenesis.

Vascular endothelial growth factor and matrix metalloproteinase 9 expression in human carotid atherosclerotic plaques: relationship with plaque destabilization via neovascularization.

BACKGROUND: The aim of this study was to evaluate the potential impact of vascular endothelial growth factor (VEGF) on carotid plaque destabilization in association with matrix metalloproteinase 9 (MMP-9) production. METHODS: Expression of VEGF and MMP-9 were determined immunohistochemically in 53 human endarterectomized atherosclerotic carotid plaques. The relationship to carotid plaque characteristics, clinical data and histological morphology was investigated. RESULTS: VEGF and MMP-9 had parallel overexpression in the inflammatory cells, especially in the neovascularized plaque lesions and around the cholesterol crystals. Strong expression of VEGF was evident in symptomatic patients (p < 0.057), in high-degree stenosis (p = 0.005), and in patients with ischemic infarct in brain scan (p = 0.021). No relation was proved between molecule expression and plaque ultrasonic characteristics. CONCLUSIONS: An intense expression of VEGF and MMP-9 in carotid plaques is related to plaque instability, high degree of stenosis and presence of symptomatic carotid occlusive disease.

Histological and lipid peroxidation changes after administration of 2-acetylaminofluorene in a rat liver injury model following selective periportal and pericentral damage.

Administration of 2-acetylaminofluorene (2-AAF) suppresses mature hepatocyte proliferation following selective periportal or pericentral damage induced by allyl-alcohol (AA) or carbon tetrachloride (CCl(4)) administration, respectively. The aim of the present study was to investigate the histological and the lipid peroxidation changes after 2-AAF administration following CCl(4) and AA treatment. The study comprised 108 male Wistar rats that were assigned in four groups: Group A: a placebo pellet was implanted in their neck and on 7th day single dosages of AA and CCl(4) were administrated. Group B: 28-day release 2-AAF pellets (7 0mg-2.5mg per day) were implanted on the neck and on 7th day received a single dose of CCl(4). Group C: 28-day release 2-AAF pellets (70-2.5mg per day) were implanted on the neck and on 7th day a single dose of AA and CCl(4) were administrated. Group D: Sham-operated. Rats of each group were sacrificed on the 9th, 11th, 13th and 21st day. Liver tissue was obtained for histological examination and blood was collected for lipid peroxidation evaluation by measuring malondialdehyde (MDA) and for liver enzymes. On the 9th and 21st day the histological score of liver necrosis was statistically higher on Groups B and C compared to Group A. Concentration of MDA in Group A was significantly higher than in Groups B and C on 9th and 11th days. Transaminase levels, however, were significantly higher in Group A on 9th day compare to the Groups B and C. In conclusion, it appears that oxidative stress was correlated with liver necrosis and with liver regeneration. Suppression of liver regeneration after 2-AAF administration leads to lower malondialdehyde concentrations.