Effect of complement C1-esterase inhibitor on brain edema and inflammation after mild traumatic brain injury in an animal model.

OBJECTIVE: Traumatic brain injury (TBI) is characterized by damage to the blood-brain barrier, inflammation, and edema formation. In this pilot study, we aimed to investigate the effects of a complement inhibitor, C1-esterase inhibitor (C1 INH), on brain edema and inflammation in a rat model of mild TBI. METHODS: Thirty-six male Sprague Dawley rats were randomly assigned to control, TBI, or TBI plus C1 INH groups. TBI and TBI plus C1 INH rats received an injection of saline or 25 IU/kg C1 INH, respectively, with TBI using a weight drop model. Control rats received saline only. Rats were subsequently euthanized and their brain tissue harvested for analysis. The primary outcome was the extent of edema as assessed by the brain's water content. Secondary outcomes included enzyme-linked immunosorbent assays to determine levels of pro-inflammatory mediators. RESULTS: Tumor necrosis factor-α levels were significantly greater in TBI rats than control rats, indicating that inflammation was generated by the weight drop impact. Brain water content following TBI was significantly different between TBI rats treated with C1-INH (78.7%±0.12), untreated TBI rats (79.3%±0.12), and control rats (78.6%±0.15, P=0.001). There was a significant decrease in C3a and interleukin 2 levels among C1 INH-treated rats compared with untreated TBI rats, but no change in levels of tumor necrosis factor-α and S100ß. CONCLUSION: C1-INH inhibited the complement pathway, suggesting that C1-INH may have a therapeutic benefit in TBI. Further studies are needed to investigate the effect of C1-INH on clinical outcomes.

A Randomized Prospective Comparison of Patient-Assessed Satisfaction and Clinical Outcomes with Radioactive Seed Localization versus Wire Localization.

Radioactive seed localization (RSL) has emerged as an alternative to wire localization (WL) in patients with nonpalpable breast cancer. Few studies have prospectively evaluated patient satisfaction and outcomes with RSL. We report the results of a randomized trial comparing RSL to WL in our community hospital. We prospectively enrolled 135 patients with nonpalpable breast cancer between 2011 and 2014. Patients were randomized to RSL or WL. Patients rated the pain and the convenience of the localization on a 5-point Likert scale. Characteristics and outcomes were compared between groups. Of 135 patients enrolled, 10 were excluded (benign pathology, palpable cancer, mastectomy, and previous ipsilateral cancer) resulting in 125 patients. Seventy patients (56%) were randomized to RSL and 55 (44%) to WL. Fewer patients in the RSL group reported moderate to severe pain during the localization procedure compared to the WL group (12% versus 26%, respectively, p = 0.058). The overall convenience of the procedure was rated as very good to excellent in 85% of RSL patients compared to 44% of WL patients (p < 0.0001). There was no difference between the volume of the main specimen (p = 0.67), volume of the first surgery (p = 0.67), or rate of positive margins (p = 0.53) between groups. RSL resulted in less severe pain and higher convenience compared to WL, with comparable excision volume and positive margin rates. High patient satisfaction with RSL provides another incentive for surgeons to strongly consider RSL as an alternative to WL.

A comparison of complication rates in early-stage breast cancer patients treated with brachytherapy versus whole-breast irradiation.

BACKGROUND: The adoption of breast brachytherapy into clinical practice for early-stage breast cancer has increased over the last several years. Studies evaluating complication rates following treatment with brachytherapy have shown conflicting results. We compared local toxicity in patients treated with brachytherapy with those treated with whole-breast irradiation (WBI). METHODS: We identified 417 early-stage breast cancer patients treated with breast-conserving surgery and radiation between 2004 and 2010, and compared 271 women treated with intracavitary brachytherapy with 146 women treated with WBI. Long-term complications were assessed using Kaplan-Meier curves with the log-rank test. RESULTS: Median follow-up was 4.6 years, and the 5-year incidence of infectious skin complications (9.7 vs. 11.0 %, p = 0.84), abscess (1.1 vs. 0 %, p = 0.15), telangiectasia (8.0 vs. 5.3 %, p = 0.35), and breast pain (14.2 vs. 9.4 %, p = 0.2) was similar between the brachytherapy and WBI cohorts. The brachytherapy cohort had a higher 5-year rate of seroma (46.5 vs. 18.5 %, p < 0.001), and fat necrosis (39.5 vs. 24.4 %, p < 0.001). Brachytherapy patients trended towards more frequent biopsies as a result of fat necrosis to rule out a recurrence (11.2 vs. 6.7 %, p = 0.13). CONCLUSIONS: Patients treated with intracavitary brachytherapy had more local toxicity, particularly seroma and fat necrosis. Patients should be counseled on the possible increased rate of long-term complications associated with brachytherapy treatment.

Infrared imaging does not predict the presence of malignancy in patients with suspicious radiologic breast abnormalities.

The NoTouch BreastScan (NTBS) is a non-invasive infrared imaging device which measures thermal gradients in breasts using dual infrared cameras and computer analysis. We evaluated NTBS as a predictor of breast cancer in patients undergoing minimally invasive biopsy. In this IRB-approved prospective trial, 121 female patients underwent NTBS prior to scheduled tissue biopsy. Twenty-two patients were excluded due to uninterpretable scans (n = 18), diagnosis of a nonprimary breast malignancy (n = 1), or no biopsy performed (n = 3) for a total of 99 patients. Five patients had bilateral breast biopsies and one patient had two ipsilateral biopsies, resulting in 105 biopsies. Patients were prospectively scanned using a high specificity mode, termed NTBS1. All 99 patients were retrospectively re-evaluated in a high sensitivity mode, NTBS2. Of 105 biopsies performed in 99 women, 33 (31.4%) were malignant and 72 (68.6%) were benign. NTBS1 demonstrated a sensitivity of 45.5% and a specificity of 88.9%. Of 94 normal contralateral breasts, 9.6% had a positive NTBS1. In the retrospective evaluation, NTBS2 demonstrated a sensitivity of 78.8% and a specificity of 48.6%. Half (50%) of the normal contralateral breasts had a positive NTBS2. NTBS does not accurately predict malignancy in women with suspicious imaging abnormalities. The higher sensitivity mode results in an unacceptable number of false positives, precluding its use. Infrared imaging did not improve the sensitivity or specificity of mammography in this clinical setting.

Effect of preoperative MRI on mastectomy and contralateral prophylactic mastectomy rates at a community hospital by a single surgeon.

Magnetic resonance imaging (MRI) use in the preoperative evaluation of newly diagnosed breast cancer (BC) patients is rising. We evaluated MRI as a function of surgical year with respect to mastectomy and contralateral prophylactic mastectomy (CPM) rates by a single surgeon. From January 2000 to December 2010, 1,279 patients with 1,296 breast cancers were identified. Our breast MRI was installed in April 2006. Mastectomy and CPM rates were evaluated by surgical year and stratified as "pre-MRI" or "MRI" depending on whether surgery occurred before or after April 2006. There was a significant increase in the percentage of patients undergoing MRI in the "pre-MRI" versus "MRI" era (17.2% versus 78.7%, p < 0.001). In contrast, mastectomy rates decreased with 29.9% undergoing mastectomy before 2006 versus 24.5% after 2006 (p = 0.038). Except for 2007, where CPM rates dropped to 7.1%, CPM rates increased from 16.7% in 2000 to 51.9% in 2010 (p = 0.033). The use of MRI, additional MRI findings and additional MRI biopsies were not associated with the decision for CPM. Age <50 was the only factor associated with CPM (RR = 2.12, p = 0.001). In our community hospital, mastectomy rates have decreased despite the increased use of preoperative MRI. MRI alone may not explain the increasing rates of mastectomy reported in other series. CPM rates have dramatically increased over time, seemingly independent of MRI use. Prospective studies are needed to assess the role of surgeon bias, along with other factors, in surgical decision making.

Breastfeeding rates and the relationship between breastfeeding and neonatal abstinence syndrome in women maintained on buprenorphine during pregnancy.

INTRODUCTION: Although a growing body of evidence suggests that buprenorphine is a safe alternative to methadone in the treatment of opioid-dependent pregnant women, little is known about breastfeeding in this population. The first objective of this study was to describe breastfeeding rates among opioid-dependent pregnant women maintained on buprenorphine in an integrated medical and behavioral health program. The second objective was to determine whether breastfeeding is related to the duration, severity, and frequency of pharmacologic treatment for neonatal abstinence syndrome (NAS). METHODS: A retrospective chart review was conducted for all infants born to opioid-dependent pregnant women treated in the integrated buprenorphine program between December 2007 and August 2012. RESULTS: Eighty-five maternal-infant pairs were identified. Sixty-five women (76%) chose to breastfeed their infants after birth; of the women who initiated breastfeeding in the hospital, 66% were still breastfeeding 6 to 8 weeks postpartum. Although the data suggest that infants who were breastfed had less severe NAS (mean peak NAS, 8.83 vs 9.65 on a modified Finnegan Scoring System) and were less likely to require pharmacologic treatment (23.1% vs 30.0%) than infants who were not breastfed, these results were not statistically significant. DISCUSSION: More than three-quarters of the opioid-dependent pregnant women in this case series chose to breastfeed after birth. Although a direct comparison of care models is not possible, the integrated model of care potentially reduced some of the barriers to breastfeeding as the women accessed all their care in a single, infant-friendly setting. Further work is needed to definitively determine whether breastfeeding mitigates NAS.

The value of 6-month interval imaging after benign radiologic-pathologic concordant minimally invasive breast biopsy.

BACKGROUND: Current National Comprehensive Cancer Network guidelines recommend repeat imaging 6-12 months after a benign radiologic-pathologic concordant image-guided breast biopsy. We hypothesized that interval imaging <12 months after benign concordant biopsy has a low cancer yield and increases health care costs. METHODS: An institutional review board-approved retrospective chart review identified 689 patients who underwent image-guided breast biopsy at Bryn Mawr Hospital between January and December 2010. Charts were evaluated for documentation of radiologic-pathologic concordance. RESULTS: Of 689 patients, 188 (27 %) had malignant pathology, 3 (0.4 %) had nonbreast pathology, and 498 (72.3 %) had benign pathology. Of 498 patients with benign findings, 44 (8.8 %) underwent surgical excision as a result of discordance, atypia, papillary lesion, or other benign finding. Of the remaining 454 patients who did not undergo excision, 337 (74.2 %) had documented radiologic-pathologic concordance. Interval imaging <12 months after benign biopsy was obtained in 182 (54.0 %) concordant patients. Five (2.7 %) patients had suspicious [American College of Radiology Breast Imaging-Reporting and Data System (BI-RADS) 4] findings on follow-up imaging. Only one breast cancer was identified, representing 0.5 % (95 % confidence interval 0-3.4) of all benign concordant patients undergoing interval imaging. The cost of detecting a missed cancer with interval imaging after benign concordant biopsy was $41,813.77 in this cohort. CONCLUSIONS: Interval imaging performed <12 months after benign concordant breast biopsy demonstrated a low yield for the detection of breast cancer and resulted in increased health care costs. Our data support the policy for discontinuation of routine interval imaging after benign concordant biopsy.

Are the American Society for Radiation Oncology guidelines accurate predictors of recurrence in early stage breast cancer patients treated with balloon-based brachytherapy?

The American Society for Radiation Oncology (ASTRO) consensus statement (CS) provides guidelines for patient selection for accelerated partial breast irradiation (APBI) following breast conserving surgery. The purpose of this study was to evaluate recurrence rates based on ASTRO CS groupings. A single institution review of 238 early stage breast cancer patients treated with balloon-based APBI via balloon based brachytherapy demonstrated a 4-year actuarial ipsilateral breast tumor recurrence (IBTR) rate of 5.1%. There were no significant differences in the 4-year actuarial IBTR rates between the "suitable," "cautionary," and "unsuitable" ASTRO categories (0%, 7.2%, and 4.3%, resp., P = 0.28). ER negative tumors had higher rates of IBTR than ER positive tumors. The ASTRO groupings are poor predictors of patient outcomes. Further studies evaluating individual clinicopathologic features are needed to determine the safety of APBI in higher risk patients.