Surgical impact of new treatments in breast cancer.

Local treatment of breast cancer with tumor-free surgical margins is the standard procedure in the treatment of T1 and small T2 breast cancers. Surgery is followed by radiation therapy, and adjuvant systemic therapy is offered depending on primary tumor characteristics, such as tumor size, grade of differentiation, number of involved axillary lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and the expression of the human epidermal growth factor 2 (HER2) receptor. Although this approach implies a higher risk of ipsilateral breast tumor recurrence, the total risk of recurrence is low (1% per year), with rates of overall survival similar to that after radical procedures. The most peripheral part of epithelial tumors, the tumor margin, is the part which is most likely to remain in loco after surgical resection. Thus, understanding the biology of the invasion front is important as these tumor cells have been reported to lose epithelial properties, such as cohesiveness and keratin expression, and to acquire features of mesenchymal cells. The parallel appearance of tumor cells in different states of cell dedifferentiation implicates a dynamic equilibrium that is determined by the induction of epithelial-mesenchymal transition (EMT). EMT has been suggested to be of prime importance for tissue and vessel invasion. Furthermore, features of EMT are associated with the activity of tumor stem cells (TSC). TSC exist in breast cancer and their appearance varies depending on the used marker profile. Consequently, intratumoral heterogeneity is reflected by the grade of EMT activation. A specific function at the invasion front is hypothesized but has not yet been proven. Nevertheless, the molecular differentiation between the tumor center and the invasion front enhances the importance of tumor-free surgical margins.

Comparison of noninvasive imaging modalities for stenosis grading in mesenteric arteries.

OBJECTIVE: To prospectively analyze duplex sonography, CTA, and MRA with respect to stenosis grading of the celiac trunk (TC) and the superior mesenteric artery (SMA), with DSA as the reference. MATERIALS AND METHODS: 52 subjects were enrolled (mean age: 71). The image quality was graded: 1-insufficient, 2-bad, 3-moderate, 4-good or 5-excellent. Stenosis was graded: 1 (< 25 %), 2 (25 - < 50 %), 3 (50 - 75 %) or 4 (75 %). Two-sided chi-square tests were used to check for correlation of stenosis grading between modalities. The weighted Cohen's kappa was calculated to assess the strength of correlation. With a threshold of 50 % for non-relevant stenosis vs. relevant stenosis, the sensitivity, specificity, PPV, NPV, and accuracy were calculated. RESULTS: The mean image quality was 3.8 ± 0.7, 3.1 ± 1.0, 4.4 ± 0.7, and 3.8 ± 0.9 for DSA, duplex sonography, CTA, and MRA, respectively. For both TC and SMA, stenosis grading reached a significant level of correlation between each noninvasive modality with DSA (p < 0.001, each). The weighted Cohen's kappa for duplex sonography/CTA/MRA was 0.94/0.93/0.74, respectively, for the TC and 0.64/0.91/0.56, respectively, for the SMA. Highest sensitivity/specificity/NPV/PPV/accuracy were found for CTA with 100 %/95 %/85 %/100 %/96 % for the TC and with na/98 %/na/100 %/98 %, respectively, for the SMA. CONCLUSION: CTA provided the best image quality, reached the highest level of agreement and significance in correlation in stenosis grading, and offered the best diagnostic accuracy.

Outcome of immediate interventions in acute dysfunctional hemodialysis fistulas.

PURPOSE: To analyze the efficacy of interventions in acute dysfunctional hemodialysis fistulas, if intervention is performed immediately as recommended by European Best Practice Guidelines for Hemodialysis. MATERIALS AND METHODS: Over 3 years, all (n = 280) patients with an acute dysfunctional hemodialysis fistula were immediately referred to angiography, irrespective of the time of day. Angiography and, if possible, interventional revision (n = 241) were performed. Three groups of interest were established: interventionalist's experience (high/low), time of day (routine hours: 7 am-4 pm/emergency hours: 4 pm-7 am), lesion type (stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+thrombotic occlusion). For statistical analysis corresponding success rates, chi-square tests (p < 0.025) and logistic regression analysis (p < 0.05) were calculated. RESULTS: The total success rate was 62 % (149/241). The success rates were: interventionalist experience high/low 71 % (79/111)/54 % (70/130), p = 0.022; time of day routine/emergency hours 68 % (93/136)/53 % (56/105), p = 0.017; lesion type stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+occlusion 82 % (94/104)/39 % (13/33)/18 % (6/33)/59 % (36/61), p < 0.001. Relevant variables due to logistic regression analysis were high experience and the lesion types stenosis and combined stenosis+occlusion with odds ratios 2.300 (p = 0.012), 12.053 (p < 0.001), 3.189 (p = 0.003). CONCLUSION: Unrestricted implementation of immediate interventions in acute dysfunctional hemodialysis fistulas requires permanent availability of experienced interventionalists. The lesion types fibrosclerotic occlusion and thrombotic occlusion offer poor success rates for interventional revision.

Interventional bleeding, hematoma and scar-formation after vacuum-biopsy under stereotactic guidance: Mammotome(®)-system 11 g/8 g vs. ATEC(®)-system 12 g/9 g.

PURPOSE: To evaluate prospectively the correlation of scar-formations after vacuum-assisted biopsy with different systems and needle-sizes and interventional bleeding/post-interventional hematoma. METHODS AND MATERIALS: Between 01/2008 and 12/2009, 479 patients underwent vacuum-assisted biopsy under stereotactic-guidance, using the Mammotome(®)-system with 11/8-gauge and ATEC(®)-system with 12/9-gauge, whereas in 178 cases with representative benign histology no surgical-biopsy after vacuum-assisted biopsy was performed and at least a 2-plane-follow-up-mammogram after 6 month post-vacuum-assisted biopsy was available. Bleeding during intervention, hematoma post-intervention and scar-tissue was scored as minimal and moderate/severe. Statistical analysis included Chi-Square-trend-test, p-value <0.05 was considered to be significant. RESULTS: Significantly more bleedings and post-interventional hematomas for 8-gauge-Mammotome(®)-system vs. 11-gauge-Mammotome(®)-system (41.9% vs. 8.4%, p<0.001/35.5% vs. 16.7%, p=0.029), no significant-differences for the ATEC(®)-systems 9-gauge vs. 12-gauge (26.9% vs. 29.7%, p=0.799/42.3% vs. 43.2%, p=0.596). 11-gauge-Mammotome(®)-system vs. ATEC(®)-12-gauge-system revealed significantly less bleedings/hematomas (8.4% vs. 29.7%, p=0.015/16.7% vs. 43.2%, p=0.001), no significant differences for the large-systems (p=0.135/p=0.352). Follow-up of Mammotome(®)-11/8-gauge-system system has shown 13.1/16.1% minimal scar-formation and 1.2/3.2% moderate/severe scars, whereas ATEC(®)-12/9-gauge-system has shown 10.8/3.8% minimal scar-formation and 0/11.5% moderate/severe scars, no significant differences. No significant difference was found when comparing Mammotome(®)-11/8-g-systems vs. ATEC(®)-12/9-g-systems (p=0.609/p=0.823). There was also no correlation between risk of scar-formation after occurrence of bleeding or hematoma with any examined VAB-system or any needle size in this study (p=0.800). CONCLUSION: Using larger needle-sizes significantly (Mammotome(®))/not significant for ATEC(®)) more interventional bleedings and post-interventional hematomas were detected, only a tendency concerning scar-formation.

[Structure and process quality of quality-assured mamma diagnostics in Schleswig-Holstein]. / Struktur- und Prozessqualität in der qualitätsgesicherten Mammadiagnostik in Schleswig-Holstein.

PURPOSE: To demonstrate the structure and process quality of quality-assured mamma diagnostics (QuaMaDi) by means of quality indicators as defined in the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis and in the National Guideline on Early Detection of Cancer in Germany. Furthermore, spatial differences and changes in the chronological sequence were analyzed. MATERIALS AND METHODS: We used administrative data as documented in the time period 2006 - 2009 in QuaMaDi in Schleswig-Holstein (SH), Germany, and analyzed quality indicators as defined in the abovementioned guidelines (absolute and relative frequencies, 95 % confidence intervals). RESULTS: Each year approximately 6 % of all women age 20 or older living in SH are examined using QuaMaDi. Only minor differences regarding age and clinical data were seen between the patients in the four regions of SH. Reference values for the quality indicators are largely reached (i. e., proportion of women with breast density ACR 3 or 4 plus additional ultrasound = 96.2 %; proportion with repeated mammography = 0.2 %). Spatial differences are only minor. In the chronological sequence, quality indicators improve, if they did not reach the reference values in the beginning, or indicate a high and constant quality. CONCLUSION: With regard to those quality indicators that were computable, reference values as defined in the guidelines were reached in 9 of 12 cases. In one case the difference between the observed value and the reference values is system-immanent and in another case the difference is less than four percentage points (reference value 90 %).

Breast ultrasound elastography--results of 193 breast lesions in a prospective study with histopathologic correlation.

PURPOSE: To evaluate the diagnostic performance of ultrasound elastography in breast masses. MATERIAL AND METHODS: 193 lesions (129 benign, 64 malignant) were analyzed with the EUB 8500 Logos-ultrasonic-unit (Hitachi Medical, Japan) and a linear-array-transducer of 7.5-13-MHz. Standard of reference was cytology (FNAfine needle aspiration) or histology (core biopsy). The elastic-score was classified according to a 6-point colour-scale (Ueno classification; 1-3 = benign, 4-5 = malignant). Conventional B-mode ultrasound (US) findings were classified according to the BI-RADS classification. Statistical analysis included sensitivity, specificity, ROC-analysis and kappa-values for intra-/interobserver reliability. RESULTS: The mean score for elasticity was 4.1 ± 0.9 for malignant lesions, and 2.1 ± 1.0 for benign lesions (p < 0.001). With a best cut-off point between elasticity scores 3 and 4, sensitivity was 96.9%, and specificity 76%. Setting a best cut-off point for conventional US between BI-RADS 4 and 5, sensitivity was 57.8%, and specificity 96.1%. Elastography provided higher sensitivity and lower specificity than conventional US, but two lesions with elasticity score 1 were false negative, whereas no lesion scored BI-RADS 1-3 were false negative. ROC-curve was 0.884 for elastography, and 0.820 for conventional US (p < 0.001). Weighted kappa-values for intra-/interobserver reliability were 0.784/0.634 for BI-RADS classification, and 0.720/0.561 for elasticity scores. CONCLUSION: In our study setting, elastography does not have the potential to replace conventional B-mode US for the detection of breast cancer, but may complement conventional US to improve the diagnostic performance.

Development of a permanently controllable rotating biopsy device, part II: Competitive in-vitro testing of a cannula-like prototype compared to established end-cut and side-notch biopsy devices.

PURPOSE: To evaluate the quantitative and qualitative efficiency of a permanently controllable biopsy-cannula prototype with lancet-like helically bent cutting edge for safer biopsy compared to established end-cut and side-notch biopsy devices. MATERIALS AND METHODS: Each of the n = 100 specimens per organ and system were obtained by the prototype, an end-cut device and a side-notch device (18 gauge each) using a bovine liver, kidney and myocardium as the biopsy tissue. Quantitatively, the number of fragments, length in mm and weight in mg of the specimen were analyzed. Qualitatively, a histopathological analysis was performed with respect to tissue fragmentation, crush artifact and adequacy of tissue (score per category min. 1 and max 3). To identify significant differences (p < 0.025), chi-square and Kruskal-Wallis tests were calculated in the statistical analysis. RESULTS: For each of the n = 300 specimens, the one-piece fragment/mean length/mean weight were n = 232 / 10.34 mm/ 4.86 mg for the prototype, n = 210 / 12.16 mm/ 5.35 mg for the end-cut system and n = 248 / 11.63 mm/ 4.08 mg for the side-notch system. The differences reached a level of significance with p < 0.001. The mean histopathological score for the prototype/end-cut system/side-notch system was 5.60 / 5.60 / 5.25 for the liver, 5.65 / 4.65 / 4.60 for the kidney and 5.05 / 5.35 / 4.85 for the myocardium. The differences did not reach a level of significance for the liver/kidney/myocardium with p = 0.665 /p = 0.186 /p = 0.436. CONCLUSION: Compared to established core biopsy systems, the biopsy-cannula prototype offers diagnostically equivalent biopsy specimen quality in an in-vitro setting in bovine liver, kidney and myocardium.

Development of a permanently controllable rotating biopsy device, Part I: theoretical considerations and in-vitro results for five different prototypes.

PURPOSE: To develop different prototypes of permanently controllable rotating biopsy devices with determination of the most efficient prototype in biopsies in bovine myocardium. MATERIALS AND METHODS: Five different prototypes of 18-gauge rotating biopsy devices were designed and constructed, four (1 - 4) with various drill-like cutting edges and one (5) cannula type with a lancet-like helically bent cutting edge. Using bovine myocardium as the biopsy tissue, n = 100 specimens per prototype were obtained, and a quantitative analysis including tissue fragmentation, length in mm and weight in mg was carried out. For statistical analysis, the chi-square test for tissue fragmentation and Kruskal-Wallis test for the parameters length and weight were calculated. RESULTS: Prototype 5 showed the highest rate of extraction of one-fragment specimens in n = 66 cases and the lowest rate of failure to obtain tissue in n = 11 cases. The mean length/weight were 4.15 mm/ 3.91 mg for prototype 1, 1.80 mm/ 1.66 mg for prototype 2, 4.61 mm/ 3.28 mg for prototype 3, 5.20 mm/ 3.74 mg for prototype 4, and 9.57 mm/ 6.97 mg for prototype 5. In all three categories, prototype 5 was significantly superior to the prototypes 1 - 4 with p < 0.001. CONCLUSION: The cannula type with a lancet-like helically bent cutting edge proved to be the most efficient prototype and may now be tested competitively against established automated biopsy devices in vitro.

Accuracy and precision in the detection of articular cartilage lesions using magnetic resonance imaging at 1.5 Tesla in an in vitro study with orthopedic and histopathologic correlation.

BACKGROUND: Magnetic resonance (MR) sequences for cartilage visualization have been the target of numerous studies, and the optimal sequence for cartilage imaging remains a matter of debate in the literature. PURPOSE: To compare MR findings with different MR sequences for the detection of cartilage lesions in fresh deep-frozen human cadaveric patellae in an in vitro setting. MATERIAL AND METHODS: Ten cadaveric patellae were imaged on a 1.5T MR scanner with a 2x2 channel carotid sandwich coil and a conventional knee coil, and compared with orthopedic findings and gold-standard histopathology. MR sequences were: a) fat-saturated (FS) proton density-weighted (PDw) turbo spin-echo (TSE) sequence (TR/TE 4000/39 ms); b) T2-weighted (T2w) double-echo steady-state (DESS) 3D water-excitation (we) sequence (TR/TE 17/4.7 ms); c) 3D-PDw-SPACE (sampling perfection with application-optimized contrasts using different flip-angle evolutions)-we sequence (TR/TE 1800/19 ms). Accuracy, Kendall's tau-b correlation, and weighted kappa coefficients were calculated. RESULTS: Accuracy for cartilage lesion detection with the FS PDw-TSE sequence and the carotid coil was 78.3%, and with the knee coil 73.9%. For the T2wDESS-3D-we sequence, the corresponding values were 69.5% and 65.2%, and for the 3D-PDw-SPACE-we sequence 65.2% and 60.8%, respectively. Kendall's tau-b correlation ranged between 0.508 for the 3D-PDw-SPACE-we sequence (knee coil) and 0.720 for the FS PDw-TSE sequence (carotid and knee coil). Weighted kappa coefficient was lowest for the 3D-PDw-SPACE-we sequence (knee coil) at 0.607, and highest for the carotid coil and FS PDw-TSE sequence at 0.779. CONCLUSION: The evaluated FS PDw-TSE sequences are superior in comparison to the T2wDESS-3D-we and 3D-PDw-SPACE-we sequences in the in vitro setting for the detection of cartilage lesions, and are comparable to results reported in the literature.

[Transjugular intrahepatic portosystemic shunt: evaluation of the impact of the stent's configuration on the patency rate]. / Transjugulärer intrahepatischer portosystemischer Shunt: Untersuchung des Einflusses der Stentkonfiguration auf die Offenheitsrate.

PURPOSE: To evaluate the impact of the configuration of the stent on the patency rate after transjugular intrahepatic portosystemic shunt with a self-expanding stent. MATERIALS AND METHODS: In total, 80 patients (60 male, 20 female; mean age 56 +/- 9.6, range 37 - 81) with a transjugular intrahepatic portosystemic shunt were evaluated. The primary technical success rate, interventional revision rate, and mean patency rate according to Kaplan-Meier were calculated. The angle of deviation of the blood flow at the portal venous inflow and central venous outflow were measured on projected angiograms (valid cases, n = 78). The following five angle groups were established: 1. portal venous inflow, 2. central venous outflow, 3. maximum, angle, 4. minimum angle, and 5. sum of both angles in the shunt system. Within each group, the Mann-Whitney Test and after dichotomic partition using the median Pearson's Chi-Square Test and Fisher's Exact Test were carried out to prove the dependency of the patency on the stent's configuration. RESULTS: The primary technical success rate was 93 %, the interventional revision rate was 28 %, and the mean patency rate was 17.5 months. The mean/standard deviation/median angle were as follows: 1. portal venous inflow 66.5 degrees / 19.2 degrees / 65 degrees , 2. central venous outflow 43.7 degrees / 14.0 degrees / 40 degrees , 3. maximum angle 69.1 degrees / 16.3 degrees / 65 degrees , 4. minimum angle 40.6 degrees / 13.3 degrees / 40 degrees , and 5. sum of both angles 110.2 degrees / 21.8 degrees / 110 degrees . The 2-sided values of significance in the Mann-Whitney Test/Chi-Square Test/Exact-Fisher Test were as follows: 1. portal venous inflow 0.112 / 0.066 / 0.083, 2. central venous outflow 0.960 / 0.919 / 1.000, 3. maximum angle 0.151 / 0.042 / 0.056, 4. minimum angle 0.578 / 0.622 / 0.632, and 5. sum of both angles 0.104 / 0.111 / 0.140. CONCLUSION: The shunt's patency rate when using a self-expanding stent is not dependent on the stent's configuration regarding the deviation of the blood flow at the portal venous inflow and central venous outflow, and the maximum, minimum and total deviation in the shunt.

[Does interventional therapy prolong the patency of hemodialysis fistulas and grafts?]. / Verlängert die radiologisch-interventionelle Therapie die Shuntnutzungsdauer bei hämodialysepflichtigen Patienten?

PURPOSE: To retrospectively evaluate procedural success and patency after endovascular treatment of acute dysfunctional hemodialysis fistulas and grafts in a non-preselected patient cohort. MATERIALS AND METHODS: 185 angiographies of hemodialysis fistulas and grafts on the upper extremities were analyzed for 120 patients (53 male, 67 female; mean-age 63.1 +/- 11.4, range 24 - 91). 70 % (n = 130) were native arteriovenous fistulas, 17 % (n = 31) were prosthetic grafts, and 13 % (n = 24) were non-specific. In total, 278 lesions requiring endovascular treatment were detected. 13 % (n = 35) of the lesions were located in the arterial inflow, 18 % (n = 49) in native arteriovenous anastomoses, 7 % (n = 19) in prosthetic grafts and 62 % (n = 171) in the venous outflow. The primary, secondary and cumulative patency after endovascular treatment was calculated. RESULTS: In 51 % (n = 94) of the cases endovascular treatment could be performed, in 8 % (n = 14) no lesion requiring treatment was detected, and in 42 % (n = 77) intervention was not considered possible. In 45 % (n = 124) of the detected lesions endovascular treatment was successful, in 18 % (n = 51) the intervention failed, and in 37 % (n = 103) intervention was not considered possible. The complication rate was 5 % (n = 10). The primary, secondary, and cumulative patency rates for 50 % of the hemodialysis fistulas and grafts after endovascular treatment were 65, 191, and 370 days, respectively. The results differed significantly from each other with p < 0.05 in the log rank test and log rank trend test. CONCLUSION: Endovascular treatment of acute dysfunctional hemodialysis fistulas and grafts is effective in restoring the patency for hemodialysis.