Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex Microparticles for Periodontitis Treatment

It is important to address the periodontitis-associated bacteria in the residual subgingival plaque after scaling and root planing to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca²⁺, and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex microparticles were synthesized from minocycline, CaCl₂, and dextran sulfate. They were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro release study was conducted to evaluate the release kinetics of minocycline from these microparticles. Agar disk diffusion assays and biofilm-grown bacteria assays were used to assess antibacterial capability. High loading efficiency (96.98% ± 0.12%) and high loading content (44.69% ± 0.03%) for minocycline were observed for these complex microparticles. Mino-Ca-DS microparticles achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18 days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated potent antimicrobial effects against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in agar disk diffusion and biofilm assays. These results suggested that the ion pairing/complexation of minocycline, Ca²⁺, and sulfonate/sulfate-bearing biopolymers can be exploited to develop complex microparticles as local delivery systems for periodontitis treatment.     

Ecological analysis of college women’s physical activity and health-related quality of life

ABSTRACT

Despite significant health benefits of regular physical activity, over 60 percent of college women do not meet recommended physical activity guidelines to promote their health and health-related quality of life (HRQoL), a comprehensive construct including physical and psychosocial health functioning. The major purpose of this study was to examine the influences of individual (e.g., self-efficacy, enjoyment), social (e.g., family and friend support), and physical environmental factors (e.g., crime safety) on college women’s physical activity and HRQoL. Participants were 235 (Mean age = 21.0 years) college women from a public research university located in the southwest region of the United States. They completed validated surveys assessing their perceptions of physical activity, HRQoL, and social ecological factors during the spring semester of 2012. The findings of three multiple linear regressions, entering individual factors first, followed by social and physical environmental factors, revealed that self-efficacy and crime safety were significantly related to physical activity. For HRQoL-physical functioning, significant factors were self-efficacy, enjoyment, and crime safety. Enjoyment was the only factor related to HRQoL-psychosocial functioning. These findings indicated that physical activity professionals need to foster safe environments, enhance self-efficacy, and provide enjoyable activities to promote college women’s physical activity and HRQoL.     

ASO Author Reflections: Undertreatment of Early-Stage Breast Cancer in Elderly Women Undergoing Lumpectomy Without Radiotherapy Increases the Risk of Locoregional Recurrence

Annals of Surgical Oncology -     

How Often Do Sentinel Lymph Node Biopsy Results Affect Adjuvant Therapy Decisions Among Postmenopausal Women with Early-Stage HR+/HER2− Breast Cancer in the Post-RxPONDER Era?

Background

The RxPONDER trial reported no benefit to chemotherapy among postmenopausal patients with HR⁺/HER2^? tumors, one to three positive nodes, and low recurrence scores, questioning the role of axillary staging in this population. Here, we evaluate the impact of sentinel lymph node biopsy (SLNB) results on adjuvant therapy decisions in postmenopausal women with HR⁺/HER2^? breast cancer.

Patients and Methods

Postmenopausal women with cT1–2N0, HR⁺/HER2^? breast cancer treated with lumpectomy and SLNB from 2012 to 2018 were identified. Receipt of nodal irradiation, indication for axillary lymph node dissection (ALND) and chemotherapy, and partial breast irradiation (PBI) eligibility were reviewed with pre- and post-SLNB results.

Results

A total of 1786 women were identified: median age 62 years, 84% with pT1 tumors, and 16% with pT2–3 tumors. Of those, 85% (n = 1525) remained pN0, 14% (n = 244) were pN1, and 1% (n = 17) were pN2–3. A total of 20 (1%) patients had > 2 positive SLNs, necessitating ALND. Pre-SLNB, 1478 women were considered PBI eligible; post-SLNB, 227 (13%) converted to PBI ineligible. In total, 58 patients with positive nodes received nodal irradiation, representing 3% of the entire cohort and 22% of pN+ patients. Overall, 1401 patients had an Oncotype DX recurrence score available, including 1273 patients with pN0 stage and 128 with pN1, with 173 (14%) and 16 (13%), respectively, having a recurrence score > 25, warranting chemotherapy.

Conclusions

While few cN0 postmenopausal women with HR⁺/HER2^? tumors had nodal pathology that warranted ALND, receipt of nodal irradiation, or indicated need for chemotherapy, in 13%, SLNB would have an impact on consideration for PBI. Among patients eligible for PBI, findings from SLNB may help refine selection among postmenopausal women with this tumor profile.

     

The Association of Surgical Margins and Local Recurrence in Women with Early-Stage Invasive Breast Cancer Treated with Breast-Conserving Therapy: A Meta-Analysis

Purpose

There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We systematically review the evidence on surgical margins in BCT for invasive breast cancer to support the development of clinical guidelines.

Methods

Study-level meta-analysis of studies reporting local recurrence (LR) data relative to final microscopic margin status and the threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression.

Results

Based on 33 studies (LR in 1,506 of 28,162), the odds of LR were associated with margin status [model 1: odds ratio (OR) 1.96 for positive/close vs negative; model 2: OR 1.74 for close vs. negative, 2.44 for positive vs. negative; (P < 0.001 both models)] but not with margin distance [model 1: >0 mm vs. 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.12); and model 2: 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.90)], adjusting for study median follow-up time. There was little to no statistical evidence that the odds of LR decreased as the distance for declaring negative margins increased, adjusting for follow-up time [model 1: 1 mm (OR 1.0, referent), 2 mm (OR 0.95), 5 mm (OR 0.65), P = 0.21 for trend; and model 2: 1 mm (OR 1.0, referent), 2 mm (OR 0.91), 5 mm (OR 0.77), P = 0.58 for trend]. Adjustment for covariates, such as use of endocrine therapy or median-year of recruitment, did not change the findings.

Conclusions

Meta-analysis confirms that negative margins reduce the odds of LR; however, increasing the distance for defining negative margins is not significantly associated with reduced odds of LR, allowing for follow-up time. Adoption of wider relative to narrower margin widths to declare negative margins is unlikely to have a substantial additional benefit for long-term local control in BCT.     

Impact of Margin Assessment Method on Positive Margin Rate and Total Volume Excised

Background

For breast-conserving surgery, the method of margin assessment that most frequently achieves negative margins without increasing the volume of tissue excised is uncertain. We examined our institutional experience with three different margin assessment methods used by six experienced breast surgeons.

Methods

Patients undergoing breast-conserving surgery for invasive carcinoma during July to December of a representative year during which each method was performed (perpendicular, 2003; tangential, 2004; cavity shave, 2011) were included. The effect of margin method on the positive margin rate at first excision and the total volume excised to achieve negative margins were evaluated by multivariable analysis, by surgeon, and by tumor size and presence of extensive intraductal component (EIC).

Results

A total of 555 patients were identified, as follows: perpendicular, 140; tangential, 124; and cavity shave, 291. The tangential method had a higher rate of positive margins at first excision than the perpendicular and cavity-shave methods (49, 15, 11 %, respectively; p < 0.0001). Median volumes to achieve negative margins were similar (55 ml perpendicular; 64 ml tangential; 62 ml cavity shave; p = 0.24). Four of six surgeons had the lowest rate of positive margins with the cavity-shave method, which was significant when compared to the tangential method (p < 0.0001) but not the perpendicular method (p = 0.37). The volume excised by the three methods varied by surgeon (p < 0.0001). The perpendicular method was optimal for T1 tumors without EIC; the cavity-shave method tended to be superior for T2–T3 tumors and/or EIC.

Conclusions

Although the cavity-shave method may decrease the rates of positive margins, its effect on volume is variable among surgeons and may result in an increase in the total volume excised for some surgeons and for small tumors without EIC.     

Perioperative Breast MRI Is Not Associated with Lower Locoregional Recurrence Rates in DCIS Patients Treated With or Without Radiation

Introduction

For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT).

Methods

A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis.

Results

There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79–1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78–2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86).

Conclusions

We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.