Biomedical subjects
Publications and source records attributed to K J Winzer.
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The international consensus conference from St. Gallen concerning the treatment of early breast cancer concluded in 2003, that sentinel node biopsy was now accepted as method allowing axillary staging in breast cancer. This procedure may avoid complete lymph node dissection in appropriate cases. Since numerous questions associated with the technique are still not defined and the procedure itself is not yet standardized, the German Society of Senology defined the conditions for the routine clinical use of sentinel node biopsy in an interdisciplinary consensus meeting.
PURPOSE: To evaluate the conspicuity of microcalcifications in magnified mammographic views of preparations obtained with full field digital mammography (FFDM), film-screen mammography (FSM), and the DIMA technique. MATERIAL AND METHODS: Twelve preparations were examined by FFDM and FSM using 1.8 x magnification and DIMA using 7 x magnification. Parameter settings were identical for all three techniques. The number of visible microcalcifications was then determined for each modality by three radiologists. As far as possible, all preparations were X-rayed at 22 kV and 10 mAS. RESULTS: Altogether 9705 calcifications were counted (DIMA: 1609/1542/1534; FFDM: 1020/753/881; FSM: 901/643/822). The total number of microcalcifications identified with the DIMA technique was 4685 as compared to 2654 with FFDM and 2366 with FSM. The calcifications counted with FFDM and FSM thus corresponded to 56.6 % and 50.5 %, respectively, of those identified with DIMA. The differences between the groups were statistically significant (F-Test, p < 0.05). CONCLUSION: Significantly more calcifications are identified when magnified mammographic views of preparations containing microcalcifications are obtained with the DIMA technique compared to FFDM or FSM. FFDM depicts markedly more calcifications than FSM. This means one should increase spatial resolution. Digital mammography offers the potential for improved visualization of microcalcifications with advanced applications.
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OBJECTIVE: To investigate the efficacy of videoendoscopic axillary lymph node dissection combined with endoscopic sentinel node detection by gamma probe and preoperative sentinel node imaging. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Four patients with breast cancer. INTERVENTION: Injection of 99mTc-nanocolloid around the tumour. RESULTS: In three patients axillary sentinel nodes were detected both before and after operation. In the remaining one it was not found. In two patients the minimally invasive approach had to be converted to conventional open surgery because of anatomical restrictions. CONCLUSION: We describe a new approach that uses a minimally invasive technique and endoscopic radioguided sentinel node biopsy in patients with breast cancer. The results of this preliminary study warrant further investigation.
Invasive breast carcinomas are characterized by a complex pattern of chromosomal alterations. We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)). Only single imbalances showed a higher incidence in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, and 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imbalances showing statistical significance were also observed in G3 and ER(-) tumors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 10q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18p11-q11, and 20q, suggesting that they contribute to a more aggressive tumor phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER(+) tumors. The ratio profiles of all cases as well as histograms are accessible at our CGH online tumor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imbalances may serve as markers for a genetic classification of invasive breast cancer.
For 20 years preoperative chemotherapy has been the treatment of choice in inflammatory breast cancer. Adjuvant chemotherapy does not show any advantages over neoadjuvant systemic chemotherapy in terms of survival of patients with breast cancer. Reduction of the size of the tumor enables the surgeon to perform more breast-conserving surgery, but the long-term results for breast tumor to recur in these patients are not yet available. At our hospital, a tumor larger than 30 mm is an indication for mastectomy. In general, only 20.6% of all patients are suitable for neoadjuvant chemotherapy. Patients with lobular carcinoma or with tumors with an extensive ductal carcinoma in situ part will not benefit from such therapy. Tumor remission following neoadjuvant chemotherapy is of prognostic relevance. The rapid therapeutic effect of neoadjuvant therapy allows short-term evaluation of this treatment.
OBJECTIVE: Digital full-field mammography has been used at the Department of Radiology of Charité Medical Center in Berlin since June 1999. This study compares the new digital technique with conventional mammography including a survey of its value in breast imaging and an outline of future prospects. MATERIAL AND METHODS: More than 1,000 of a total of over 5,000 mammographies performed between June 1999 and April 2000 have been obtained using the digital full-field mammography system Senographe 2000D (GE Medical Systems). The digital mammograms were compared with previous conventional films and conventional mammographies performed during the same period (Philips UC Diagnost, Senographe DMRplus). RESULTS: Digital mammographies were equal to conventional ones in all cases and seemed to be superior in detecting microcalcifications in dense glandular tissue. Adequate assessment was possible despite the lower spatial resolution compared to conventional mammography. Additional magnified images were obtained with both techniques for differentiating microcalcifications. CONCLUSIONS: Digital full-field mammography appears to be at least equal to the conventional technique and even superior in some respects. In our experience, the lower spatial resolution of digital mammography has no major disadvantages. The digital system provides new options for electronic storage of mammograms, telemammography, and computer-aided diagnosis.
PURPOSE: A procedure for performing intraoperative digital radiography of diagnostic breast specimens directly in the operating suite with teleradiologic assessment by a radiologist is presented. The efficiency of this procedure is compared with that of conventional magnification mammography performed in the radiology department. MATERIAL AND METHODS: Thirty-six specimen radiographs obtained by conventional magnification mammography were compared with 38 intraoperative digital magnification radiographs (DIMA Soft P42 prototype, Feinfocus Inc., Garbsen). The radiographs were assessed for lesion conspicuity and time savings for the surgeon, anesthesiologist, and radiologist. RESULTS: The new procedure identified all 38 labeled pathological lesions, and the conventional technique likewise had a detection rate of 100% (36/36). The new technique resulted in considerable time savings for the surgeon and the radiologist. The duration of surgery was shorter and the time interval from removal of the specimen to reporting of the results was reduced from about 23 min to about 13 min. A single radiograph was sufficient for complete visualization of the specimen in all cases. CONCLUSION: Digital intraoperative specimen radiography considerably reduces the time of surgery depending on the local conditions and is highly accurate in locating a suspicious area within the tissue.
The relation between estrogen receptors (ER) and argyrophilic nucleolar organizer regions (AgNORs) in situ within human breast cancer cells was analyzed. For AgNOR measurements in 49 invasive breast carcinomas, a new reproducible staining method for dual demonstration of ER and AgNORs was applied. Quantitative AgNOR variables were determined in ER-positive and ER-negative tumor cells by digital image analysis. The relationships between AgNOR parameters of ER-positive and ER-negative cells and other prognostic factors of breast cancer [Bloom-Richardson-Grading and growth fraction (Ki-67 index)] were investigated. A higher AgNOR content in ER-negative cells and a special clustering phenomenon in ER-positive tumor cells were found. Correlation with other criteria of malignant potential could be exclusively demonstrated for ER-negative cells. ER-negative cells of breast cancer can be characterized as the more malignant and possibly prognosis-dictating cell fraction. Thus, ER-negative cells probably contribute more to the progression of the tumor disease and furthermore to the prognosis than ER-positive cells. We recommend measurement AgNORs exclusively in ER-negative cells of breast cancer.
OBJECTIVE: To determine the diagnostic and prognostic value of argyrophilic nucleolar organizer regions (AgNORs) in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and microinvasive ductal carcinoma (MDCA) of the breast. STUDY DESIGN: Image analysis of histologic sections from biopsies of 46 breast ADH and DCIS and 18 cases of MDCA. Determination of morphometric features of cell nuclei and nucleolar organizer regions by using AMBA software system. Data were compared with the estrogen receptor/progesterone receptor (ER/PR) content as well as with the growth fraction, determined immunohistochemically. RESULTS: AgNOR number and total AgNOR area increased from ADH to DCIS. The highest values were recorded in cases of DCIS with microinvasion. Differences between ADH and intraductal or microinvasive ductal carcinoma were statistically significant. Within the group of intraductal carcinomas, the lowest values were measured in the solid type and highest values in the comedo type. A correlation was found between AgNOR features and growth fraction but not between these features and ER/PR status. CONCLUSION: Selected AgNOR features are relevant for differentiation between ADH and DCIS as well as between low and high grade DCIS and microinvasive ductal carcinoma. Therefore, objective and reproducible data obtained by AgNOR analysis may allow better evaluation of the prognostic significance of these lesions.
For the histological verification of suspicious non-palpable small breast tumors, the three-dimensional breast biopsy applied as cylindrical extirpation using the ABBI system is the optimal solution at present. Because of the possibility of performing mammography during the operation, errors of localization can be corrected and incorrect incisions avoided. Taking the three radiomorphologically leading symptoms into consideration--suspicious microcalcification, focal shadow and structural irregularity--it can be stated that the digital mammography of the ABBI system is more sensitive than the conventional one for detecting microcalcification, but focal shadow and structural irregularity are detected less well by digital technique. These structures should be preoperatively marked by using sonography. After the complete removal of suspicious microcalcification checked by digital mammography during the operation, residual tumor might be found in a second excision when histologically invasive or intraductal tumor terminations reach the excision margin (R1 resection). Thirteen invasive and 8 intraductal carcinomas were found in 80 cases of cylindrical extirpation using the ABBI system. In 7 procedures carried out to exclude an in-breast recurrence, 3 intraductal carcinomas and 1 invasive carcinoma were observed. In 8 of 12 invasive carcinomas and in 1 of 5 intraductal carcinomas, breast-conserving therapy was indicated. Two cases of invasive carcinoma fulfilled the criteria applied (minimal tumor-free margin > 2 mm, no extensive intraductal component) to use the ABBI cylinder as lumpectomy without a second excision to follow.
Comparative genomic hybridization was applied to map DNA gains and losses in 39 invasive ductal breast carcinomas. Frequent abnormalities included gains on chromosomal regions 1q, 8q, 11q12-13, 16p, 19, 20q and X as well as frequent losses on 1p, 5q, 6q, 9p, 11q, 13q and 16q. Furthermore, frequent losses on 4q (20 cases) and 21q (14 cases) were found for the first time in this tumour type. High copy number amplifications were observed at 8q12-24, 11q11-13 and 20q13-ter. Highly differentiated tumours were associated with gains on 1q and 11q12-13 along with losses on 1p21-22, 4q, 13q, 11q21-ter. Undifferentiated breast carcinomas were characterized by additional DNA imbalances, i.e. deletions of 5q13-23, all of chromosome 9, the centromeric part of chromosome 13 including band 13q14 and the overrepresentation of chromosome X. We speculate that these changes are associated with tumour progression of invasive ductal breast cancer.
PURPOSE: A prospective study on the differentiation of breast lesions was carried out using experimental combination schemes of mammography and automatic sonography. MATERIALS AND METHODS: X-ray mammograms and a B image from automatic sonography of 39 malignant and 41 benign lesions as well as 40 cases without lesions were separately examined by four experienced diagnosticians. The observers differentiated the findings mammographically and by measurement in the B images. RESULTS: For two examiners the combination of mammography and automatic sonography gave with regard to the differentiation of breast lesions an improvement in sensitivity of 3 or 5% and in specificity of 31 and 18%, respectively, as compared to mammography alone while for the other two examiners an improved specificity of 21 and 36%, respectively, was accompanied by an 8 and 10% decrease in sensitivity as compared to mammography alone. CONCLUSIONS: The differentiating criteria from automatic sonography and mammography can, in principle, be used to evaluate the dignity of breast lesions. However, an optimization is necessary since the improvement in specificity does not compensate the loss in sensitivity.
A short overview is given demonstrating the possibilities and limits of the frozen section technique in mammary carcinoma. The accuracy of this method in diagnostic pathology of the mammary gland is up to 97% when applied by experienced pathologists. In case of breast cancer it may be difficult to determine the maximum of tumor size and the minimum tumor-free distance to the resection margin which are significant for a breast-conserving operation. There are further limits when an atypical ductal hyperplasia (ADH) should be differentiated from a ductal carcinoma in situ (DCIS) and when in case of DCIS microinvasion is to be proven. Nevertheless, intraoperative frozen section technique is unrenunciable for breast cancer surgery. Mistakes can be avoided in most of the cases, if surgeon and pathologist will closely cooperate and if both are fully aware of the limitations of the method.
A new technique for breast imaging is presented. This technique combines radiographic mammography directly with automated ultrasound. The combined examination, which is performed without decompression of the breast, yields the conventional mammography films as well as a complete set of B-mode scans and ultrasound projections. These can be geometrically matched with each other in a definitive manner. A prototype of the device was first used in a pilot study of 50 patients followed by a study of an additional 450 patients with a total of 492 breast lesions, of which 269 were confirmed by histology or cytology. The results show that X-ray and ultrasound are complementary in the detection of cancer. The use of an experimental mode of image interpretation for combined mammography and automated ultrasound reduced the number of mammographically suspicious findings that ultimately turned out to be benign. These results were also confirmed in two blind studies including a total of 160 histologically or cytologically confirmed lesions and 40 cases without lesions. With further technical advancement of the technique aimed at rapid and easy application and confirmation of the results obtained so far, the combination of mammography and automated ultrasound might be introduced into a routine clinical setting.
For non-palpable lesions detected radiographically alone, lumpectomy after needle-localization is currently performed. Specimen radiography provides an indirect proof of complete excision of the mammographic abnormality. Up to now, intraoperative mammography of the operated breast has not been possible. Digital intraoperative mammography is now possible with the ABBI-system, which will be introduced in this article. In a pilot study, we have investigated, whether it is possible to excise small carcinomas with the ABBI stereotactic biopsy device (maximum diameter 20 mm) without compromising breast conserving therapy. In a prospective study, 69 patients were diagnosed or treated using the ABBI-system. In all 60 patients with a primary lesion, a cylindrical excision was performed. Of these, 11 invasive and 5 intraductal carcinomas were diagnosed. 7 of the invasive and 2 of the intraductal cancers were treated with breast conserving surgery. In 9 cases, an in-breast recurrence was suspected. In 7 of these a cylindrical excision was performed. One invasive and 3 intraductal carcinomas were found and mastectomy was performed in these four patients. In two patients with the suspicion of an in-breast recurrence, the ABBI-system was used to perform a core-needle biopsy. In one patient, the biopsy finding was positive and mastectomy was performed. Patients with lesions close to the chest wall are not suited for the ABBI-system. The postoperative course was uneventful in all cases, the cosmetic result after breast-conserving therapy was very good. The advantages of this new method consist in the reliable stereotactic localization of suspicious lesions and in the fast intraoperative imaging.
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