A prospective study of the removal rate of imaged breast lesions by an 11-gauge vacuum-assisted biopsy probe system.

BACKGROUND: More than 1,000,000 breast biopsies are performed each year as a result of abnormalities identified by imaging techniques. This prospective study was designed to determine whether complete removal of the imaged evidence of an abnormal mammogram or ultrasonogram could be achieved with percutaneous image-guided procedures using an 11-gauge vacuum-assisted biopsy probe. METHODS: Forty-five women over the age of 18 years entered the study; 50 breast lesions were identified by ultrasonography or mammography. Biopsies were obtained using an 11-gauge vacuum-assisted probe. At 6 months after biopsy, ultrasonography or mammography examinations of the biopsy site were performed. RESULTS: Forty-five lesions (90%) were completely removed. At 6 months after biopsy, 82% of the sites were lesion free. The percentage of nonrecurring lesions at 6 months after surgery was inversely related to the size of the original lesion. CONCLUSION: This device allows biopsies to be successfully combined with complete removal of the imaged lesion in a one-step minimally invasive procedure.

Negative predictive value of sonography with mammography in patients with palpable breast lesions.

OBJECTIVE: This study was performed to determine the negative predictive value of sonography with mammography in evaluating palpable breast lesions. MATERIALS AND METHODS: Four hundred twenty patients with 455 palpable breast lesions were retrospectively identified from our mammography database as having negative mammographic and sonographic results. For patients diagnosed with breast cancer, images and medical records were reviewed to determine whether the palpable lesion evaluated on sonography and mammography corresponded to the patient's breast cancer. On the basis of the number of breast cancers that correlated to the palpable areas imaged, the negative predictive value of sonography with mammography was determined. RESULTS: Sixty-two of the 420 patients in the study group were already diagnosed with breast carcinoma, and eight new carcinomas were diagnosed during the study period. Only one of six ipsilateral cancers corresponded to a palpable lesion that had a negative imaging evaluation. This lesion was diagnosed as an invasive lobular cancer, hard and fixed at physical examination. Imaging and clinical follow-up of the remaining patients showed no abnormality at the sites of previously investigated palpable abnormalities. The mean imaging follow-up was 25 months. The negative predictive value of sonography and mammography in the setting of a palpable lesion was 99.8%. CONCLUSION: The negative predictive value of sonography with mammography is high, and together these imaging modalities can be reassuring if follow-up is planned when the physical examination is not highly suspicious. However, if the physical examination is suspicious, biopsy should not be delayed.

Stereotactic breast biopsy: a practical approach.

The continuing increase of women participating in mammographic screening has resulted in a rise in the number of nonpalpable abnormalities identified. The development of minimally invasive and cost-effective methods to achieve accurate histologic diagnosis is needed. Stereotactic needle core biopsy had been used to reduce the number of women requiring needle-directed open surgical biopsies for benign disease. The team approach is essential for implementation of these newer diagnostic and interventional modalities. The surgeon has always taken the responsibility for coordinating the diagnostic and treatment components of appropriate breast care. Therefore, surgeons must continue to integrate new technology into their practices. The extensive experience of more than 3000 stereotactic biopsies performed at The Breast Center has provided the background for discussing the technical aspects of the procedure. The appropriate workup and subsequent indications for patient selection are reviewed. Pre and postprocedural patient considerations are addressed. This should provide an introduction to the basic principles of stereotactic needle core biopsy for implementation into a surgical practice.

Autoproteolysis of herpes simplex virus type 1 protease releases an active catalytic domain found in intermediate capsid particles.

The UL26 gene of herpes simplex virus type 1 (HSV-1) encodes a 635-amino-acid protease that cleaves itself and the HSV-1 assembly protein ICP35cd (F. Liu and B. Roizman, J. Virol. 65:5149-5156, 1991). We previously examined the HSV protease by using an Escherichia coli expression system (I. C. Deckman, M. Hagen, and P. J. McCann III, J. Virol. 66:7362-7367, 1992) and identified two autoproteolytic cleavage sites between residues 247 and 248 and residues 610 and 611 of UL26 (C. L. DiIanni, D. A. Drier, I. C. Deckman, P. J. McCann III, F. Liu, B. Roizman, R. J. Colonno, and M. G. Cordingley, J. Biol. Chem. 268:2048-2051, 1993). In this study, a series of C-terminal truncations of the UL26 open reading frame was tested for cleavage activity in E. coli. Our results delimit the catalytic domain of the protease to the N-terminal 247 amino acids of UL26 corresponding to No, the amino-terminal product of protease autoprocessing. Autoprocessing of the full-length protease was found to be unnecessary for catalysis, since elimination of either or both cleavage sites by site-directed mutagenesis fails to prevent cleavage of ICP35cd or an unaltered protease autoprocessing site. Catalytic activity of the 247-amino-acid protease domain was confirmed in vitro by using a glutathione-S-transferase fusion protein. The fusion protease was induced to high levels of expression, affinity purified, and used to cleave purified ICP35cd in vitro, indicating that no other proteins are required. By using a set of domain-specific antisera, all of the HSV-1 protease cleavage products predicted from studies in E. coli were identified in HSV-1-infected cells. At least two protease autoprocessing products, in addition to fully processed ICP35cd (ICP35ef), were associated with intermediate B capsids in the nucleus of infected cells, suggesting a key role for proteolytic maturation of the protease and ICP35cd in HSV-1 capsid assembly.

Deletion of the VP16 open reading frame of herpes simplex virus type 1.

VP16 (also called Vmw65 and alpha TIF) is a structural protein of herpes simplex virus type 1 (HSV-1) that trans-induces HSV-1 immediate-early gene transcription. This report describes an HSV-1 VP16 deletion mutant that was constructed and propagated in a cell line transformed with a VP16 expression vector. The VP16 deletion mutant replicated like wild-type HSV-1 during infection of the VP16-expressing cell line. Deletion mutant virions propagated in this cell line contained wild-type, cell-derived VP16 protein that was recruited during virion assembly and was functional for immediate-early gene trans-induction. The mutant failed to replicate during subsequent infection of cells that do not express VP16, as determined in plaque assays and single-step replication assays. The deletion mutant induced nearly normal levels of viral DNA synthesis and capsid production during these infections, but it induced slightly lower levels of viral DNA encapsidation and appeared by transmission electron microscopy to be defective in further steps of virion maturation. A genetic revertant of the deletion mutant that was restored for VP16-coding sequences exhibited fully wild-type replication properties in both VP16-expressing and nonexpressing cells. The absence of VP16 protein synthesis at late times of HSV-1 infection prevents the production of infectious progeny virus and correlates with a profound defect in HSV-1 particle assembly.

DNA binding by the herpes simplex virus type 1 ICP4 protein is necessary for efficient down regulation of the ICP0 promoter.

The herpes simplex virus type 1 ICP4 and ICP0 polypeptides are immediate-early proteins that positively and negatively regulate expression of other viral genes in trans. ICP4 has recently been shown to bind DNA bearing the consensus sequence 5'-ATCGTCNNNN(T/C)CG(A/G)C-3', present upstream of a number of viral genes. To test the hypothesis that this DNA-binding activity is involved in ICP4-mediated gene regulation, site-specific mutagenesis was employed to mutate the version of this sequence in the promoter of the ICP0 gene. The mutation eliminated detectable binding of ICP4 to the promoter as measured in vitro by a gel electrophoresis band shift assay. The ability of the mutated ICP0 promoter to direct synthesis of a reporter gene was also investigated in a transient transfection assay. Whereas ICP4 was found to transactivate the wild-type ICP0 promoter two- to threefold, the mutated promoter was transactivated seven- to ninefold. In assays containing the ICP0 transactivator gene, ICP4 down regulated the wild-type promoter far more efficiently than the mutated promoter. Finally, both the wild-type and mutated ICP0 promoters exhibited a similar response to ICP4 in transfections that included a vector expressing the viral transactivator protein VP16. These experiments suggest that the sequence-specific DNA-binding activity of ICP4 is an essential element of its role as a negative regulator of gene expression.