Guiding Breast-Conserving Surgery in Patients After Neoadjuvant Systemic Therapy for Breast Cancer: A Comparison of Radioactive Seed Localization with the ROLL Technique

Background

Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-^99mTc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 (¹²⁵I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated.

Methods

All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-^99mTc technique (n = 83) or with ¹²⁵I seed localization (n = 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed.

Results

Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-^99mTc technique and ¹²⁵I seed localization.

Conclusions

The ROLL-^99mTc technique and ¹²⁵I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because ¹²⁵I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer ¹²⁵I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.     

Hollow Microparticles as a Superior Delivery System over Solid Microparticles for the Encapsulation of Peptides

Purpose

Peptides are gaining significant interests as therapeutic agents due to their high targeting specificity and potency. However, their low bioavailability and short half-lives limit their massive potential as therapeutics. The use of dense, solid particles of biodegradable polymer as a universal carrier for peptides also has its challenges, such as inefficient peptide release and low bioactivity. In this paper, it was established that hollow microparticles (h-MPs) instead of solid microparticles (s-MPs), as peptide carriers, could improve the release efficiency, while better preserving their bioactivity.

Methods

Glucagon like Peptide-1 (GLP-1) was encapsulated as a model peptide. Mass loss, average molecular weight changes, intraparticle pH, polymer-peptide interaction and release studies, together with bioactivity assessment of the peptide for s-MPs and h-MPs were systematically analyzed and evaluated for efficacy.

Results

The intraparticle pH of s-MPs was as low as 2.64 whereas the pH of h-MPs was 4.99 by day 7. Consequently, 93% of the peptide extracted from h-MPs was still bioactive while only 58% of the peptide extracted from s-MPs was bioactive. Likewise, the cumulative release of GLP-1 by day 14 from h-MPs showed a cumulative amount of 88?±?8% as compared to 33?±?6% for s-MPs.

Conclusions

The cumulative release of peptide can be significantly improved, and the bioactivity can be better preserved by simply using h-MPs instead of s-MPs as carriers.

     

Combining neuroimaging and behavior to discriminate children with attention deficit-hyperactivity disorder with and without prenatal alcohol exposure

Brain Imaging and Behavior - In many patients, ostensible idiopathic attention deficit-hyperactivity disorder (ADHD) may actually stem from covert prenatal alcohol exposure (PAE), a...     

Use of EEG to Diagnose ADHD

Electroencephalography (EEG) has, historically, played a focal role in the assessment of neural function in children with attention deficit hyperactivity disorder (ADHD). We review here the most recent developments in the utility of EEG in the diagnosis of ADHD, with emphasis on the most commonly used and emerging EEG metrics and their reliability in diagnostic classification. Considering the clinical heterogeneity of ADHD and the complexity of information available from the EEG signals, we suggest that considerable benefits are to be gained from multivariate analyses and a focus towards understanding of the neural generators of EEG. We conclude that while EEG cannot currently be used as a diagnostic tool, vast developments in analytical and technological tools in its domain anticipate future progress in its utility in the clinical setting.     

Wall shear stress in the stented superficial femoral artery in peripheral arterial disease

Objective

Local changes in wall shear stress (WSS) contribute to vascular wall thickening and subsequent stenosis. Restenosis after stenting is a major concern, especially in the superficial femoral artery (SFA) of patients with peripheral arterial disease (PAD). Local alterations in WSS after stenting might contribute to restenosis/reocclusion. To test the hypothesis that WSS is impaired along the stented SFA segment, we studied the profile of WSS along the femoro-popliteal axis after stent placement in a cross-sectional design.

Methods

Eighty-seven patients with PAD (89 limbs) were included one day after stenting of the SFA. Flow velocities (peak and mean) and vessel diameter were measured by duplex ultrasound in five predefined segments along the femoro-popliteal axis, at rest and after exercise (30 toe raises); WSS (peak and mean) was calculated from flow velocities, vessel diameter and whole blood viscosity.

Results

WSS progressively declined along the stented segment at rest (peak WSS, p < 0.0001; mean WSS, p < 0.05); after exercise, WSS increased in all segments (all p < 0.001), but, again, progressively declined along the stent (peak WSS, p < 0.0001; mean WSS, p < 0.05). The internal vessel diameter remained unchanged after exercise in the stented and in the non-stented parts of the femoro-popliteal axis (all p > 0.05).

Conclusion

In PAD patients with SFA stenting WSS is impaired along the femoro-popliteal axis. The consequences of this finding in terms of local effects on the vessel wall that might favor restenosis/reocclusion needs further investigation.     

Angiotensin II induces mitochondrial dysfunction and promotes apoptosis via JNK signalling pathway in primary mouse calvaria osteoblast

Objectives

This present study was designed to investigate the effects of Angiotensin II on mitochondrial functions, ROS generation and c-jun N-terminal kinases (JNK) signalling pathway-mediated cell apoptosis in mouse calvaria osteoblasts.

Methods

Calvaria osteoblast were isolated and cultured. The cells were separated into two groups—control and treated groups—where the latter was stimulated with angiotensin II (Ang II). Mitochondrial reactive oxygen species (ROS) and superoxide production were measured. Intracellular ATP levels were also detected. The cell proliferation rate was determined for the two groups. Protein production such as Anti-Bax, Bcl-2, COX IV and activation of c-jun N-terminal kinases signal (JNK) pathway was measured by enzyme-linked immunosorbent assay (ELISA) methods and Western blotting in this study.

Results

Ang II treated cells showed significantly higher levels of superoxide production compared to the control group (p < 0.05). Conversely, Ang II induced inhibitory effects on mitochondrial respiratory enzyme complexes, cause membrane potential dissipation, ATP loss and promote ROS generation, cell apoptosis in cultured osteoblasts. In addition, JNK phosphorylations were involved in activating the mitochondria-dependent apoptotic pathway following Ang II stimulation, as pre-treatment of JNK-specific inhibitor SP600125 could rescue osteoblast cells from apoptosis by enhancing the anti-apoptotic protein Bcl-2 expressions, suppressing the translocation of Bax from cytosol into mitochondria, blocking cytochrome C release and caspase-3 activation.

Conclusions

Ang II stimulates osteoblast apoptosis via suppression of the mitochondrial respiratory enzymes, membrane potential and cellular ATP productions. Clinical application with Ang II-stimulated osteoblast could be used for modelling or bone resorption in the oral region.