Effects of Extracorporeal Shock Wave-Mediated Transdermal Local Anesthetic Drug Delivery on Rat Caudal Nerves

Cavitation plays a substantial role in the clinical effects of extracorporeal shock wave therapy (ESWT). It is also generally accepted as a major mechanism in sonophoresis. To identify the enhancing effect of extracorporeal shock wave-mediated transdermal drug delivery, 24 Wistar rats were randomly assigned to four groups: (i) topical application of a eutectic mixture of local anesthetics (EMLA); (ii) 1-MHz ultrasound; (iii) ESWT pre-treatment combined with EMLA application; (iv) ESWT concurrent with EMLA application on rat tails. The degree of anesthesia was assessed using the amplitude and latency of sensory nerve action potentials within 5?min after a 60-min EMLA application. The results indicated that ESWT pre-treatment and concurrent ESWT accelerated the anesthetic effects of the EMLA cream on the tail nerve (p?<?0.05). This finding might indicate that shock wave-mediated transdermal drug delivery is possible during the ESWT period.     

Application of galactose-modified liposomes as a potent antigen presenting cell targeted carrier for intranasal immunization

The mucosal immune system produces secretory IgA (sIgA) as the first line of defense against invasion by foreign pathogens. Our aim was to develop a galactose-modified liposome as a targeted carrier which can be specifically recognized by macrophage, one of the most important antigen presenting cells. First, galactose was covalently conjugated with 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine (DLPE) to give a targeted ligand, a galactosyl lipid. The galactosyl lipid was then incorporated into a liposomal bilayer to form a galactosylated liposome carrier. Further, the ovalbumin (OVA) was encapsulated into the galactosylated liposome carriers and mice were intranasally immunized. Confocal laser scanning microscopy and flow cytometry analysis showed that the targeted galactosylated liposome carrier had a higher uptake rate than unmodified liposomes. The targeted galactosylated liposome induced higher levels of tumor necrosis factor-α and interleukin-6 production than unmodified liposomes (P < 0.05). Furthermore, 6-week-old BALB/c female mice immunized with the OVA-encapsulated targeted galactosylated liposome had significantly higher OVA-specific s-IgA levels in the nasal and lung wash fluid (P < 0.05). In addition, the targeted galactosylated liposome simultaneously augmented the serum IgG antibody response. In summary, the OVA-encapsulated targeted galactosylated liposome induced significantly higher mucosal IgA and systemic IgG antibody titers and is a potential antigen delivery carrier for further clinical applications.     

Surgical Resection Versus Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Propensity Score Analysis

Background

The long-term survival in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) who received surgical resection (SR) or transarterial chemoembolization (TACE) remains unclear. We compared the efficacy of SR and TACE by using a propensity score analysis.

Methods

A total of 247 and 181 HCC patients with PVTT undergoing SR and TACE, respectively, were evaluated. One hundred eight pairs of matched patients were selected from each treatment arm by using a propensity score analysis.

Results

Of all patients, the estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 85 versus 60 %, 68 versus 42 %, and 61 versus 33 %, respectively (p < 0.001). Patients selected for SR were significantly younger and had better liver functional reserve, performance status, and smaller tumor burden. In the propensity model, the survival benefit of SR remained significant. The estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 84 versus 71 %, 69 versus 50 %, and 59 versus 35 %, respectively (p = 0.004). The two groups of patients in the propensity score analysis were similar in baseline characteristics. In the Cox proportional hazards model, patients receiving TACE had a 2.044-fold increased risk of mortality compared with patients receiving SR (95 % confidence interval: 1.284–3.252, p = 0.003).

Conclusions

For either unselected patients or patients in the propensity model, SR provides significantly better long-term survival than TACE. SR should be considered as a priority treatment in this subgroup of HCC patients.     

Percutaneous ethanol ablation of intrahepatic arterial pseudoaneurysm: A case report

Hepatic arterial pseudoaneurysm is a rare but potentially fatal condition that requires prompt management. We report a case of hepatic arterial pseudoaneurysm developed after radiofrequency ablation of a hepatocellular carcinoma. The patient was successfully treated with percutaneous absolute ethanol injection under ultrasound guidance. Follow-up studies with ultrasound and computed tomography for 2 years after treatment revealed no evidence of local recurrence of hepatocellular carcinoma and of the pseudoaneurysm.     

Performance Status Enhances the Selection of Treatment for Patients with Hepatocellular Carcinoma Within the Milan Criteria

Background

Performance status (PS) is closely linked with survival in patients with hepatocellular carcinoma (HCC). We investigated its impact on treatment strategy for small HCC(s).

Methods

A total of 360 and 362 HCC patients within the Milan criteria undergoing surgical resection (SR) and radiofrequency ablation (RFA), respectively, were prospectively enrolled. Patients were classified into PS 0 (n = 558) and PS ≥1 (n = 164) groups. Propensity score analysis was performed, and 168 and 35 matched pairs were selected from patients with PS 0 and ≥1, respectively.

Results

The SR group was younger and had a higher male-to-female ratio, higher prevalence of hepatitis B, lower prevalence of hepatitis C, better PS, better liver functional reserve, and larger tumor burden than the RFA group (all p < 0.05). Among patients with PS 0, the SR group was consistently younger, less cirrhotic, and had larger tumor burden (all p < 0.05). The long-term survival was comparable between SR and RFA group in patients with PS 0. After propensity score matching, SR provided significantly better long-term survival than RFA for patients within the Milan criteria classified as PS 0 (p = 0.016); the Cox proportional hazards model showed consistent results. There was no significant difference of overall survival between the SR and RFA group in patients with PS ≥1 before or after propensity score matching (both p > 0.05).

Conclusions

For HCC patients within the Milan criteria and classified as PS 0, SR provides a better long-term survival compared with RFA. Performance status may enhance treatment selection and stratify the risk of survival in these patients.     

Preconditioning threshold of brief pressure overload of the left ventricle

BackgroundWe previously reported that pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits. The threshold of pressure overload was investigated in this study.MethodsPressure overload of the left ventricle was induced by partial snare of the ascending aorta in anesthetized, open-chest rabbits. Systolic left ventricular pressure (SLVP) was elevated 50% or 30% above baseline value by varying the degree of partial snaring. Different duration of pressure overload, including 10 minutes, 5 minutes, 3 minutes, or 2 minutes, was applied to determine the threshold of protective effects. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and reperfusions. Ten minutes after different pretreatment, 1 hour occlusion of the left anterior descending coronary artery followed by 3 hours reperfusion was done to induce MI. The size of area at risk and MI were determined by blue dye injection and triphenyl tetrazolium chloride staining after experiments.ResultsPressure overload increase of SLVP 50% above baseline value for 10 minutes, 5 minutes, and 3 minutes significantly reduced MI size (18.5 ± 3.6%, 21.4 ± 1.9% and 21.6 ± 1.7%, respectively, vs. 26.6 ± 1.0% in the control group, mean ± standard deviation, p < 0.01). A 30% increase of SLVP by pressure overload for 10 minutes, 5 minutes and 3 minutes also significantly decreased MI size (20.5 ± 2.5%, 21.6 ± 2.3%, and 21.5 ± 2.3%, p < 0.01). Ischemic preconditioning significantly decreased MI size (19.9 ± 2.8%, p < 0.001). Pressure overload to elevate SLVP 50% or 30% above baseline value for 2 minutes did not significantly alter MI size (25.0 ± 2.3% and 26.0 ± 1.7%, p = 0.122 and p = 0.457). Two episodes of 2 minutes pressure overload did not significantly decrease MI size (25.0 ± 2.2% and 25.5 ± 2.2%, p = 0.118 and p = 0.281). The hemodynamics, area at risk, and mortality were not significantly different among all groups of animals.ConclusionPressure overload to raise SLVP either 50% or 30% above baseline value reduced MI size. A minimum duration of 3 minutes was necessary to induce the protective effects.     

Brief pressure overload of the left ventricle preconditions rabbit myocardium against infarction

Background

Several nonischemic stimuli have been shown to precondition myocardium. We investigated cardioprotective effects and underlying mechanisms of brief pressure overload of the left ventricle in this study.

Methods

Brief pressure overload of the left ventricle was achieved by two 10-minute partial snaring of the ascending aorta so that systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. Ten minutes after different pretreatments, myocardial infarction was induced by a 60-minute coronary artery occlusion followed by 3-hour reperfusion. Area at risk and myocardial infarct was determined by blue dye injection and triphenyl tetrazolium chloride staining.

Results

The myocardial infarct size, expressed as percentage of area at risk, was significantly reduced in the pressure overload group (15.9% ± 2.9%, p < 0.001, n = 9) as well as in the ischemic preconditioning group (14.9% ± 1.9%, p < 0.001, n = 9) versus the control group (30.0% ± 6.9%, n = 10). Pretreatment with a blocker of stretch-activated ion channels (gadolinium, 40 μmol/kg, intravenous) abolished the protection induced by pressure overload and ischemic preconditioning. Gadolinium itself did not alter the extent of infarct. There was no significant difference in hemodynamics, area at risk, and mortality among all groups of animals.

Conclusions

Brief pressure overload of the left ventricle by partial snaring of the ascending aorta preconditioned rabbit myocardium against infarction. The underlying mechanism might be related to activation of stretch-activated ion channels.     

Validation of the HCC-MELD for dropout probability in patients with small hepatocellular carcinoma undergoing locoregional therapy

Abstract: Background:  The model for end-stage liver disease (MELD) is used in prioritizing cirrhotic patients awaiting liver transplantation. Patients with small hepatocellular carcinoma (HCC) are eligible candidates. An HCC-MELD equation was recently proposed to predict the dropout rate of HCC patients on the waiting list. This study aimed to validate the accuracy of this equation.
Methods:  We investigated 390 patients with small HCC who were candidates for liver transplantation and underwent locoregional therapy.
Results:  The estimated probability of dropout according to the equation was 8.2% for T1 stage and 13.5% for T2 stage HCC (p < 0.0001). The actual disease progression rate at three months was 2.1% for T1 and 3.0% for T2 stage HCC. At six months, the progression rate was 5.3% for T1 stage and 6.8% for T2 stage. The area under receiver operating characteristic curve of the HCC-MELD equation was 0.81 at three months and 0.80 at six months. Patients undergoing radiofrequency ablation (RFA) had significantly lower dropout rates compared with other treatment groups according to the equation (p = 0.0007). The actual tumor progression rate was also the lowest for the RFA group at both three and six months.
Conclusion:  The HCC-MELD equation is a feasible predictive model for patients with small HCC undergoing locoregional therapy.     

Surface modification and characterization of chitosan or PLGA membrane with laminin by chemical and oxygen plasma treatment for neural regeneration

Attachment to and proliferation on the substrate are deemed important considerations when Schwann cells (SCs) are to be seeded in synthetic nerve grafts. Good attachment is a prerequisite for the SCs to survive. Fast proliferation will yield large numbers of SCs in a short time, which appears to be promising for stimulating peripheral nerve regeneration. However, surface properties are the dominating factor in influencing the interactions between cells and synthetic nerve grafts. The aim of this study was to investigate the surface effects of laminin modified PLGA and chitosan membranes after chemical method and plasma treatment. Laminin, the extracellular matrix protein, is a permissive protein for SCs adhesion used in neural regeneration. The surface properties of laminin modified membranes were assayed by BCA, FTIR and XPS analysis. Results showed that laminin was covalently bonded onto the surface of both PLGA and chitosan membranes either by chemical method or by oxygen plasma treatment. The cell affinity of the laminin modified membranes was verified by Schwann cells culturing. Our results also indicate that oxygen plasma is indeed a better method to incorporate laminin onto the surface of membrane. Laminin-modified chitosan membrane significantly increases SCs attachment and affinity for directing peripheral nerve regeneration.