Clip migration in stereotactic biopsy

BACKGROUND: Needle localization breast biopsy (NLBB) is the standard for removal of breast lesions after vacuum assisted core biopsy (VACB). Disadvantages include a miss rate of 0% to 22%, a positive margin rate of approximately 50%, and vasovagal reactions (approximately 20%). We hypothesized that clip migration after VACB is clinically significant and may contribute to the positive margin rates seen after NLBB. METHODS: We performed a retrospective review of postbiopsy films in patients who had undergone VACB with stereotactic clip placement for abnormal mammograms. We measured the distance between the clip and the biopsy site in standard two view mammograms. The location of the biopsy air pocket was confirmed using the prebiopsy calcification site. The Pythagorean Theorem was used to calculate the distance the clip moved within the breast. Pathology reports on NLBB or intraoperative hematoma-directed ultrasound-guided breast biopsy (HUG, which localizes by US the VACB site) were reviewed to assess margin status. RESULTS: In all, 165 postbiopsy mammograms on patients who had VACB with clip placement were reviewed. In 93 evaluable cases, the mean distance the clip moved was 13.5 mm +/- 1.6 mm, SEM (95% CI = 10.3 mm to 16.7 mm). Range of migration was 0 to 78.3 mm. The median was 9.5 mm. In 21.5% of patients the clip was more than 20 mm from the targeted site. Migration of the clip did not change with the age of the patient, the size of the breast or location within the breast. In the subgroup of patients with cancer, margin positivity (including those with close margins) after NLBB was 60% versus 0% in the HUG group. CONCLUSIONS: Significant clip migration after VACB may contribute to the high positive margin status of standard NLBBs. Surgeons cannot rely on needle localization of the clip alone and must be cognizant of potential clip migration. HUG as an alternative biopsy technique after VACB eliminates operator dependency on clip location and may have superior results in margin status.     

Improving quality of care for acute myocardial infarction: The Guidelines Applied in Practice (GAP) Initiative

Context  Quality of care of patients with acute myocardial infarction (AMI) has received intense attention. However, it is unknown if a structured initiative for improving care of patients with AMI can be effectively implemented at a wide variety of hospitals. Objective  To measure the effects of a quality improvement project on adherence to evidence-based therapies for patients with AMI. Design and Setting  The Guidelines Applied in Practice (GAP) quality improvement project, which consisted of baseline measurement, implementation of improvement strategies, and remeasurement, in 10 acute-care hospitals in southeast Michigan. Patients  A random sample of Medicare and non-Medicare patients at baseline (July 1998–June 1999; n = 735) and following intervention (September 1–December 15, 2000; n = 914) admitted at the 10 study centers for treatment of confirmed AMI. A random sample of Medicare patients at baseline (January–December 1998; n = 513) and at remeasurement (March–August 2001; n = 388) admitted to 11 hospitals that volunteered, but were not selected, served as a control group. Intervention  The GAP project consisted of a kickoff presentation; creation of customized, guideline-oriented tools designed to facilitate adherence to key quality indicators; identification and assignment of local physician and nurse opinion leaders; grand rounds site visits; and premeasurement and postmeasurement of quality indicators. Main Outcome Measures  Differences in adherence to quality indicators (use of aspirin, -blockers, and angiotensin-converting enzyme [ACE] inhibitors at discharge; time to reperfusion; smoking cessation and diet counseling; and cholesterol assessment and treatment) in ideal patients, compared between baseline and postintervention samples and among Medicare patients in GAP hospitals and the control group. Results  Increases in adherence to key treatments were seen in the administration of aspirin (81% vs 87%; P = .02) and -blockers (65% vs 74%; P = .04) on admission and use of aspirin (84% vs 92%; P = .002) and smoking cessation counseling (53% vs 65%; P = .02) at discharge. For most of the other indicators, nonsignificant but favorable trends toward improvement in adherence to treatment goals were observed. Compared with the control group, Medicare patients in GAP hospitals showed a significant increase in the use of aspirin at discharge (5% vs 10%; P<.001). Use of aspirin on admission, ACE inhibitors at discharge, and documentation of smoking cessation also showed a trend for greater improvement among GAP hospitals compared with control hospitals, although none of these were statistically significant. Evidence of tool use noted during chart review was associated with a very high level of adherence to most quality indicators. Conclusions  Implementation of guideline-based tools for AMI may facilitate quality improvement among a variety of institutions, patients, and caregivers. This initial project provides a foundation for future initiatives aimed at quality improvement.      

A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.      

Contortrostatin, a dimeric disintegrin from Agkistrodon contortrix contortrix, inhibits breast cancer progression

We report the results of a multidisciplinary study on the inhibitory effect of a snake venom disintegrin, contortrostatin, a 13.5 kDa homodimeric protein isolated from Agkistrodon contortrix contortrix (southern copperhead) venom, on breast cancer progression. We demonstrate that contortrostatin binds to integrins and blocks the adhesion of human breast cancer cells (MDA-MB-435) to extracellular matrix (ECM) proteins including fibronectin and vitronectin, but it has no effect on adhesion of the cells to laminin and Matrigel. Contortrostatin also prevents invasion of MDA-MB-435 cells through an artificial Matrigel basement membrane. Daily local injection of contortrostatin (5 microg per mouse per day) into MDA-MB-435 tumor masses in an orthotopic xenograft nude mouse model inhibits growth of the tumor by 74% (p = 0.0164). More importantly, it reduces the number of pulmonary macro-metastasis of the breast cancer by 68% (p < 0.001), and micro-metastasis by 62.4% (p < 0.001). Contortrostatin is not cytotoxic to cancer cells, and does not inhibit proliferation of the breast cancer cells in vitro. However, contortrostatin inhibits angiogenesis induced by the breast cancer, as shown by immunohistochemical quantitation of the vascular endothelial cells in tumor tissue removed from the nude mice. We have identified alpha(v)beta3, an important integrin mediating cell motility and tumor invasion, as one of the binding sites of contortrostatin on MDA-MB-435 cells. We conclude that contortrostatin blocks alpha(v)beta3, and perhaps other integrins, and thus inhibits in vivo progression.     

MAKING SENSE OF CLINICAL TRIALS IN GLAUCOMA - GLAUCOMA LASER TRIAL (GLT)

The Glaucoma Laser Trial (GLT), the first randomized controlled clinical trial of glaucoma treatment, substantially influenced subsequent ophthalmic research. Principles of randomization, objective determination of glaucomatous progression with standard definitions of visual field damage, stepped treatment regi-     

Laser lithotripsy: animal studies of safety and efficacy

The safety and efficacy of pulsed tunable dye laser fragmentation of common bile duct stones was assessed in pigs. Laser pulses were conducted through a flexible quartz fiber that was in direct contact with stones that had been surgically implanted into the common bile duct. All calculi were rapidly fragmented into small pieces without significant damage to the common bile duct. The immediate and delayed effects of pulsed lasers on the common bile duct were also evaluated. The common bile duct demonstrated a high tolerance to laser-induced damage even when the laser was discharged directly into the bile duct wall. These results suggest that laser lithotripsy can be performed in humans with a high degree of safety and efficacy.