The added diagnostic value of dynamic contrast-enhanced MRI at 3.0 T in nonpalpable breast lesions.

OBJECTIVE: To investigate the added diagnostic value of 3.0 Tesla breast MRI over conventional breast imaging in the diagnosis of in situ and invasive breast cancer and to explore the role of routine versus expert reading. MATERIALS AND METHODS: We evaluated MRI scans of patients with nonpalpable BI-RADS 3-5 lesions who underwent dynamic contrast-enhanced 3.0 Tesla breast MRI. Initially, MRI scans were read by radiologists in a routine clinical setting. All histologically confirmed index lesions were re-evaluated by two dedicated breast radiologists. Sensitivity and specificity for the three MRI readings were determined, and the diagnostic value of breast MRI in addition to conventional imaging was assessed. Interobserver reliability between the three readings was evaluated. RESULTS: MRI examinations of 207 patients were analyzed. Seventy-eight of 207 (37.7%) patients had a malignant lesion, of which 33 (42.3%) patients had pure DCIS and 45 (57.7%) invasive breast cancer. Sensitivity of breast MRI was 66.7% during routine, and 89.3% and 94.7% during expert reading. Specificity was 77.5% in the routine setting, and 61.0% and 33.3% during expert reading. In the routine setting, MRI provided additional diagnostic information over clinical information and conventional imaging, as the Area Under the ROC Curve increased from 0.76 to 0.81. Expert MRI reading was associated with a stronger improvement of the AUC to 0.87. Interobserver reliability between the three MRI readings was fair and moderate. CONCLUSIONS: 3.0 T breast MRI of nonpalpable breast lesions is of added diagnostic value for the diagnosis of in situ and invasive breast cancer.

[Suppose a mammary carcinoma is absent from the surgical specimen]. / Stel dat het mammacarcinoom ontbreekt in het resectiepreparaat.

In three women aged 53, 51, and 42 respectively, who were treated by breast-conserving surgery for mammary carcinoma, the cancer was not found in the surgical specimen. For both patient and treating physician it is rather worrying when there is no good explanation for the fact that a histologically proven breast cancer cannot be detected in the surgical specimen without neoadjuvant therapy having been given. It is important to revise the needle biopsies, to exclude mix up of patient materials, to totally include the resected specimen in the pathological examination and to perform addition imaging of the remaining breast, preferably with MRI. An explanation may be that biopsy has removed such an amount of tumour tissue that the remains are not found. If no flaws are apparent, adjuvant radiotherapy and further adjuvant therapy on indication suffices.

Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome - MONET - study.

BACKGROUND: In recent years there has been an increasing interest in MRI as a non-invasive diagnostic modality for the work-up of suspicious breast lesions. The additional value of Breast MRI lies mainly in its capacity to detect multicentric and multifocal disease, to detect invasive components in ductal carcinoma in situ lesions and to depict the tumor in a 3-dimensional image. Breast MRI therefore has the potential to improve the diagnosis and provide better preoperative staging and possibly surgical care in patients with breast cancer. The aim of our study is to assess whether performing contrast enhanced Breast MRI can reduce the number of surgical procedures due to better preoperative staging and whether a subgroup of women with suspicious nonpalpable breast lesions can be identified in which the combination of mammography, ultrasound and state-of-the-art contrast-enhanced Breast MRI can provide a definite diagnosis. METHODS/DESIGN: The MONET - study (MR mammography Of Nonpalpable BrEast Tumors) is a randomized controlled trial with diagnostic and therapeutic endpoints. We aim to include 500 patients with nonpalpable suspicious breast lesions who are referred for biopsy. With this number of patients, the expected 12% reduction in surgical procedures due to more accurate preoperative staging with Breast MRI can be detected with a high power (90%). The secondary outcome is the positive and negative predictive value of contrast enhanced Breast MRI. If the predictive values are deemed sufficiently close to those for large core biopsy then the latter, invasive, procedure could possibly be avoided in some women. The rationale, study design and the baseline characteristics of the first 100 included patients are described. TRIAL REGISTRATION: Study protocol number NCT00302120.

The finding of invasive cancer after a preoperative diagnosis of ductal carcinoma-in-situ: causes of ductal carcinoma-in-situ underestimates with stereotactic 14-gauge needle biopsy.

BACKGROUND: For the evaluation of nonpalpable lesions of the breast, image-guided 14-gauge automated needle biopsy is increasingly replacing wire-localized excision. When ductal carcinoma-in-situ (DCIS) is diagnosed at core biopsy, invasive cancer is found in approximately 17% of excision specimens. These so-called DCIS underestimates pose a problem for patients and surgeons, because they generally cause extension of treatment. We evaluated DCIS underestimates in detail to assess reasons for missing the invasive component at core biopsy. This evaluation also included a histological comparison with true DCIS (DCIS at core biopsy and excision). METHODS: Between 1997 and 2000, DCIS was diagnosed at 14-gauge needle biopsy in 255 patients. In 41 cases (16%), invasive cancer was found at excision. We performed a thorough histopathological and radiological review of all these DCIS underestimates, including a histological comparison with core biopsy specimens of 32 true DCIS cases. We assessed the main reason for missing the invasive component at core biopsy. RESULTS: Causes for DCIS underestimates were categorized into "mainly radiological" (n = 20), "mainly histopathological" (n = 15), and "histological disagreements" (n = 6). High-grade DCIS and periductal inflammation in core biopsies made a DCIS underestimate 2.9 and 3.3 times more likely, respectively. CONCLUSIONS: A variety of radiological and histopathological reasons contribute to the DCIS underestimate rate. Approximately half of these are potentially avoidable.

The Dictyostelium CARMIL protein links capping protein and the Arp2/3 complex to type I myosins through their SH3 domains.

Fusion proteins containing the Src homology (SH)3 domains of Dictyostelium myosin IB (myoB) and IC (myoC) bind a 116-kD protein (p116), plus nine other proteins identified as the seven member Arp2/3 complex, and the alpha and beta subunits of capping protein. Immunoprecipitation reactions indicate that myoB and myoC form a complex with p116, Arp2/3, and capping protein in vivo, that the myosins bind to p116 through their SH3 domains, and that capping protein and the Arp2/3 complex in turn bind to p116. Cloning of p116 reveals a protein dominated by leucine-rich repeats and proline-rich sequences, and indicates that it is a homologue of Acan 125. Studies using p116 fusion proteins confirm the location of the myosin I SH3 domain binding site, implicate NH(2)-terminal sequences in binding capping protein, and show that a region containing a short sequence found in several G-actin binding proteins, as well as an acidic stretch, can activate Arp2/3-dependent actin nucleation. p116 localizes along with the Arp2/3 complex, myoB, and myoC in dynamic actin-rich cellular extensions, including the leading edge of cells undergoing chemotactic migration, and dorsal, cup-like, macropinocytic extensions. Cells lacking p116 exhibit a striking defect in the formation of these macropinocytic structures, a concomitant reduction in the rate of fluid phase pinocytosis, a significant decrease in the efficiency of chemotactic aggregation, and a decrease in cellular F-actin content. These results identify a complex that links key players in the nucleation and termination of actin filament assembly with a ubiquitous barbed end-directed motor, indicate that the protein responsible for the formation of this complex is physiologically important, and suggest that previously reported myosin I mutant phenotypes in Dictyostelium may be due, at least in part, to defects in the assembly state of actin. We propose that p116 and Acan 125, along with homologues identified in Caenorhabditis elegans, Drosophila, mouse, and man, be named CARMIL proteins, for capping protein, Arp2/3, and myosin I linker.

In vitro refolding of heterodimeric CapZ expressed in E. coli as inclusion body protein.

CapZ is a heterodimeric Ca(2+)-independent actin binding protein which plays an important role in organizing the actin filament lattice of cross-striated muscle cells. It caps the barbed end of actin filaments and promotes nucleation of actin polymerization, thereby regulating actin filament length. Here we report the expression of the two muscle-specific isoforms alpha2 and beta1, from chicken in Escherichia coli as individual subunits using the pQE60 expression vector and the subsequent renaturation of the functional CapZ heterodimer from inclusion bodies. Optimal renaturation conditions were obtained both by simultaneous refolding of urea-solubilized subunits and by rapid dilution into a buffer containing 20% glycerol, 5 mM EGTA, 2 mM DTT, 1 mM PMSF, and 100 mM Tris, pH 7.4. The refolding mixture was incubated for 24 h at 15 degrees C and the protein was concentrated by ultrafiltration. Biochemical characterization of the recombinant heterodimer revealed actin binding activities indistinguishable from those of native CapZ as purified from chicken skeletal muscle. Using the same protocol, we were able to refold the beta1, but not the alpha2 isoform as a single polypeptide, indicating a role for beta1 as a molecular template for the folding of alpha2. The reported recombinant approach leads to high yields of active heterodimer and allows the renaturation and characterization of the beta subunit.

The millennium bug--do we have the right antibiotics?

This article introduces readers to the scope of the Year 2000 (Y2K) issue. In addition to describing how this problem came to be, the author examines the extent of the problem as defined by professionals in information technology. The author also explores what the cost of fixing the problem may be and what industry is doing to mitigate the effects the Y2K bug will have on patient care, supplies, and financial operations. The author expresses the need for caregivers to have a greater interest in the problem and to ask questions about what is being done at individual institutions.

[On the nonexistence of propionic acid in various kinds of breeds (author's transl)]. / Uber das Nichtvorkommen von Propionsäure in Roggen- und Mischbrot

Analyses of 45 samples of sour dough and various kinds of bread have shown that no appreciable amounts of propionic acid are formed during sour dough fermentation. Bread has no natural propionic acid content.