Can acoustic structural quantification be used to characterize the ultrasound echotexture of the peripheral zone of breast lesions?

BACKGROUND: Besides mammography, breast ultrasound is the most important imaging modality for women with suspected breast cancer. New software tools bear high potential for improved detectability and specification of malignant breast lesions. OBJECTIVE: To compare the halo depicted around malignant breast lesions by ultrasound using Acoustic Structure Quantification (ASQ) of raw image data with the echogenic rim seen in B-mode ultrasound. METHODS: This retrospective study included 37 women for whom conventional B-mode ultrasound of the breast and ASQ were available as well as histopathology findings for comparison. Software tools were used to measure the halo area or echogenic rim and tumor area and calculate halo-to-lesion ratios for the two ultrasound modes. Six inexperienced readers characterized the breast lesions based on this information. Specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. ANOVA, the Wilcoxon test, and ROC curve analysis were performed. RESULTS: There was a linear relationship between ASQ-based and B-mode-based halo-to-lesion ratios; however, a systematic error was also noted. ASQ-derived ratios tended to be higher for breast lesions with lymphangioinvasion (p = 0.051, n.s.) and higher N-stages (p > 0.925, n.s.), while there was no correlation with other markers. Because of the significantly greater conspicuity of peritumoral halos in the ASQ mode, inexperienced readers achieved greater sensitivity (78% vs. 74%) and specificity (75% vs. 71%) and higher NPVs (75% vs. 71%) and PPVs (78% vs. 74%) compared with B-mode images. Greater halo conspicuity affected the identification of malignant lesions with both modes; ASQ was found to be particularly well suited (FBimage (1,100) = 19.253, p < 0.001; FASQ (1,100) = 52.338, p < 0.001). The inexperienced readers were significantly more confident about their diagnosis using the ASQ maps (z = -3.023, p = 0.003). CONCLUSIONS: We conclude that the halo in ASQ and the echogenic rim in B-mode ultrasound are attributable to different morphologic correlates. ASQ improves diagnostic accuracy and confidence of inexperienced examiners because of improved halo visibility.

Shame in Medical Education: A Randomized Study of the Acquisition of Intimate Examination Skills and Its Effect on Subsequent Performance.

THEORY: Although medical students are exposed to a variety of emotions, the impact of emotions on learning has received little attention so far. Shame-provoking intimate examinations are among the most memorable events for students. Their emotions, however, are rarely addressed during training, potentially leading to withdrawal and avoidance and, consequently, performance deficits. However, emotions of negative valance such as shame may be particularly valuable for learning, as they might prompt mental rehearsal. We investigated the effect of shame on learning from the perspective of cognitive load theory. HYPOTHESES: We hypothesized that (a) training modality determines state shame, (b) state shame directly affects the quality of a clinical breast examination as one example of a shame-provoking exam, and (c) students who experience shame during training outperform those who just discuss the emotion during subsequent performance assessments. METHOD: Forty-nine advanced medical students participated in a randomized controlled, single-blinded study. After a basic, low-fidelity breast examination training, students were randomized to further practice either on a high-fidelity mannequin including a discussion of their emotions or by examining a standardized patient's real breasts. Last, all students conducted a breast examination in a simulated doctor's office. Dependent variables were measures of outcome and process quality and of situational shame. RESULTS: Students training with a standardized patient experienced more shame during training (p < .001, d = 2.19), spent more time with the patient (p = .005, d = 0.89), and documented more breast lumps (p = .026, d = 0.65) than those training on a mannequin. Shame interacted with training modality, F(1, 45) = 21.484, p < .001, η2 = 0.323, and differences in performance positively correlated to decline in state shame (r = .335, p = .022). CONCLUSIONS: Students experiencing state shame during training do reenact their training and process germane load-in other words, learn. Furthermore, altering simulation modality offers a possibility for educators to adjust the affective component of training to their objectives.

In vivo high-resolution magnetic resonance elastography of the uterine corpus and cervix.

OBJECTIVES: To apply 3D multifrequency MR elastography (3DMMRE) to the uterus and analyse the viscoelasticity of the uterine tissue in healthy volunteers considering individual variations and variations over the menstrual cycle. METHODS: Sixteen healthy volunteers participated in the study, one of whom was examined 12 times over two menstrual cycles. Pelvic 3DMMRE was performed on a 1.5-T scanner with seven vibration frequencies (30-60 Hz) using a piezoelectric driver. Two mechanical parameter maps were obtained corresponding to the magnitude (|G (*) |) and the phase angle (φ) of the complex shear modulus. RESULTS: On average, the uterine corpus had higher elasticity, but similar viscosity compared with the cervix, reflected by |G (*) |uterine corpus = 2.58 ± 0.52 kPa vs. |G (*) |cervix = 2.00 ± 0.34 kPa (p < 0.0001) and φ uterine corpus = 0.54 ± 0.08, φ cervix = 0.57 ± 0.12 (p = 0.428). With 2.23 ± 0.26 kPa, |G (*) | of the myometrium was lower in the secretory phase (SP) compared with that of the proliferative phase (PP, |G (*) | = 3.01 ± 0.26 kPa). For the endometrium, the value of |G (*) | in SP was 68% lower than during PP (PP, |G (*) | = 3.34 ± 0.42 kPa; SP, |G (*) | = 1.97 ± 0.34 kPa; p = 0.0061). CONCLUSION: 3DMMRE produces high-resolution mechanical parameter maps of the uterus and cervix and shows sensitivity to structural and functional changes of the endometrium and myometrium during the menstrual cycle. KEY POINTS: MR elastography provided for the first time spatially resolved viscoelasticity maps of uterus. Uterine corpus had a higher elasticity, but similar viscosity compared with cervix. The stiffness of both endometrium and myometrium decreases during the menstrual cycle.

TSI ultrasound elastography for the diagnosis of chronic allograft nephropathy in kidney transplanted patients.

PURPOSE: To answer the question whether the TSI (tissue strain imaging) sonoelastography technique can contribute to the diagnosis of chronic renal allograft damage. MATERIAL AND METHODS: A prospective study of 112 patients between June 2010 and April 2011 was conducted to compare elastography data with biopsy results and laboratory parameters in order to determine whether any correlations exist. Elastography parameters were acquired with a high-end ultrasound system and analyzed using the semiquantitative strain ratio. For comparison, patients were divided into three groups based on biopsy findings (Banff classification): group A: biopsy not necessary; group B: Banff grade I; group C: Banff grades II and III. Correlations were assessed by means of correlation (Pearson) and regression analysis. Differences between ordinal groups were tested for statistical significance by the Mann-Whitney U test. RESULTS: Mean patient age was 54.2 ± 15.01 years. Fifty-nine percent of the patients were male. The calculated TSI strain ratio of groups A and C differed significantly (p = 0.024). Groups B and C (p = 0.056) and groups A and B (p = 0.88) showed no significant difference. The TSI strain ratio did not correlate with glomerular filtration rate (r = 0.105) or creatinine (r = 0.092). CONCLUSION: The TSI sonoelastography technique can contribute to the differentiation of different stages of renal graft damage (according to Banff classification). However, significant results were not observed for all investigated features. The TSI technique should be further evaluated in future studies including larger numbers of patients.

Intraoperative ultrasound: improved resection rates in breast-conserving surgery.

AIM: The objective of this study was the investigation of a possible improvement of tumor resection rate, i.e. R0 vs. R1 resection when intraoperative ultrasound evaluation of tissue margins is used during breast-conserving surgery (BCS). PATIENTS AND METHODS: A total of 250 cases were evaluated retrospectively. The impact of ultrasound analysis onto clean margin rates was evaluated. A subgroup analysis assessed histology, stage, and neoadjuvant therapy with respect to R0 resection rate and ultrasound evaluation. RESULTS: Of 250 BCS cases 84, (33.6%) underwent intraoperative ultrasound and 166 (66.4%) did not. Clean primary surgical margins (R0) were demonstrated for 218 (87.2%) patients after histological analysis. R0 resection was achieved in 81 (96.4%) patients in the ultrasound group compared to 137 (82.5%) in the control group. The difference between the two groups is significant. CONCLUSION: This study revealed a significant increase in R0 resection rates when intraoperative ultrasound was used to evaluate surgical margins.

3D breast ultrasound: a significant predictor in breast cancer reduction under pre-operative chemotherapy.

BACKGROUND: The objective was the investigation of a possible predictive quantitative impact of initial tumor sphericity, measured by 3D sonography, on response to pre-operative chemotherapy. PATIENTS AND METHODS: This 3D ultrasound study was conducted on 41 consecutive primary breast cancer patients who received pre-operative epirubicin and paclitaxel chemotherapy; the tumors were measured by 3D sonography and by pathology after chemotherapy. Sphericity was defined as the ratio of the smallest to the largest extent by 3D sonography. RESULTS: A predictive impact of initial tumor sphericity on response to pre-operative chemotherapy was quantitatively identified for the first time. Sphericity was a significant predictor of pathological complete remission with a rank difference of 0.34 or about 1/3 i.e., spherical tumors were more likely to show successful remission. CONCLUSION: Tumor sphericity as defined from 3D sonography could be predictive of response to pre-operative chemotherapy regimens; prospective investigation is suggested.

Benefits of early and prolonged fulvestrant treatment in 848 postmenopausal advanced breast cancer patients.

Response to fulvestrant and survival in postmenopausal hormone-sensitive advanced breast cancer was investigated within a non-randomized, In-Practice Evaluation Program, with the aim of optimizing treatment decisions. 848 patients (median age 64 years; 52% co-morbidity; 78% prior palliative therapy; median 4 prior regimens) received monthly fulvestrant injections (250 mg/month) and were followed-up three-monthly for 9 months. Clinical benefit (PFS ≥ 24 weeks) occurred in 532/848 (62.7%); stable disease (SD) in 627/848 patients (74%), including 62 complete and 177 partial responses. Best response was delayed in 115 patients. Estimated 9-month overall survival (OS) was 89%; 9-month event-free survival (EFS) was 71%. Indicators of disease aggressiveness affected response and survival, but number of fulvestrant cycles was the key OS and EFS determinant. The patients with SD at 3 months benefitted from continued fulvestrant. Excluding deaths, 7 serious adverse events occurred (none attributable to fulvestrant). No new or unexpected safety issues arose; 90% of the patients and physicians rated fulvestrant tolerability as "very good" or "good". In the largest prospective, fulvestrant-treated cohort to date, advanced breast cancer patients achieving SD or better after 3 months of treatment gained survival benefit by prolonging fulvestrant therapy-independent of disease and treatment history.

Vascular endothelial growth factor receptor 2-specific microbubbles for molecular ultrasound detection of prostate cancer in a rat model.

OBJECTIVES: To investigate whether rat prostate cancer can be detected by means of molecular ultrasound (US) using target-specific microbubbles versus a nonspecific contrast agent. MATERIALS AND METHODS: A total of 20 Copenhagen rats were randomly examined 75 to 104 days after orthotopic implantation of G-Dunning rat prostatic tumor cells was using a high-end US system and either 1.2 mL/kg of the nonspecific agent A or 0.1 mL/kg of the target-specific agent B, containing vascular endothelial growth factor receptor 2 binding peptide. Contrast inflow (areas under the curve analysis) was determined during the first 30s, and all microbubbles were destroyed in the scan plane by means of the flash technique 20 minutes after intravenous administration to investigate specific accumulation of individual bubbles in tumors. Differences between normal prostate tissue and tumor were analyzed using luminance images. Sonographically determined tumor localization and extent were compared with magnetic resonance imaging and histology. RESULTS: The median tumor size in the 20 rats determined on US (2.3 mm) and magnetic resonance imaging (2.4 mm) showed a very high correlation (r = 0.92, P = 0.01). Both agent A and agent B demonstrated higher vascularization of tumor periphery compared with normal prostate (P < 0.05) based on contrast inflow and areas under the curve analysis. Twenty minutes after administration, luminance for agent B in the tumor was significantly higher (P = 0.003) compared with nonspecific agent A (11.8-0.1). In consensus reading, the increase in signal intensity of the tumor compared with normal prostate tissue was significantly higher for agent B (P = 0.005), whereas no significant difference was found for agent A (P = 0.180). CONCLUSIONS: The target-specific contrast agent was superior to the unspecific US contrast agent both with regard to early inflow analysis and specific accumulation in prostate cancer after 20 minutes.

Tumor-specific correlation of tumor M2 pyruvate kinase in pre-invasive, invasive and recurrent cervical cancer.

UNLABELLED: The aim of this study was to investigate the diagnostic value of tumor M2 pyrurate kinase (Tu-M2-PK) as a tumor marker in patients with pre-invasive (CIN), invasive (PCC) and recurrent (RCC) cervical cancer. MATERIALS AND METHODS: Plasma samples were investigated from 125 patients, comprising 50 cases of CIN (I-III), 51 of PCC (FIGO I-IV) and 24 of RCC, before treatment. Tu-M2-PK levels were determined by using a quantitative sandwich enzyme immunoassay. RESULTS: With the increase in disease severity from CIN to PCC to RCC, levels of Tu-M2-PK significantly increased (p<0.001). Levels of Tu-M2-PK significantly increased with respect to the FIGO stage (p<0.001) and had significantly higher values in node+ patients (p=0.028). There was no significant difference in Tu-M2-PK levels in CIN I-III patients (p=0.626). Patients with distant metastasis had significantly elevated levels of Tu-M2-PK (p<0.001). CONCLUSION: Tu-M2-PK can be used as a marker to differentiate between malignant and premalignant cervical lesions. In addition, the concentration of Tu-M2-PK correlates with the clinical stage of the disease.

Significant differentiation of focal breast lesions: calculation of strain ratio in breast sonoelastography.

RATIONALE AND OBJECTIVES: Initial data suggest that elastography can improve the specificity of ultrasound in differentiating benign and malignant breast lesions. The aim of this study was to compare elastography and B-mode ultrasound to determine whether the calculation of strain ratios (SRs) can further improve the differentiation of focal breast lesions. MATERIALS AND METHODS: A total of 227 women with histologically proven focal breast lesions (113 benign, 114 malignant) were included at two German breast centers. The women underwent a standardized ultrasound procedure using a high-end ultrasound system with a 9-MHz broadband linear transducer. B-mode scans and sonoelastograms were analyzed by two experienced readers using the Breast Imaging Reporting and Data System criteria. SRs were calculated from a tumor-adjusted region of interest (mean color pixel density) and a comparable region of interest placed in the lateral fatty tissue. Sensitivity, specificity, and cutoff values were calculated for SRs (receiver-operating characteristic analysis). RESULTS: The women had a mean age of 54 years (range, 19-87 years). The mean lesion diameter was 1.6 +/- 0.9 cm. Sensitivity and specificity were 96% and 56% for B-mode scanning, 81% and 89% for elastography, and 90% and 89% for SRs. An SR cutoff value of 2.45 (area under the curve, 0.949) allowed significant differentiation (P < .001) of malignant (mean, 5.1 +/- 4.2) and benign (mean, 1.6 +/- 1.0) lesions. The quantitative method of SR calculation was superior to subjective interpretation of sonoelastograms and B-mode scans, with a positive predictive value of 89% compared to 68% and 84% for the other two methods. CONCLUSIONS: Calculation of SRs contributes to the standardization of sonoelastography with high sensitivity and allows significant differentiation of benign and malignant breast lesions with higher specificity compared to B-mode ultrasound but not elastography.

Side-effects of pre-operative epirubicin-paclitaxel therapy in primary breast cancer associated with tumor biology.

BACKGROUND: The objective of this analysis is to identify relationships between side-effects, tumor biological factors and response to pre-operative epirubicin and paclitaxel therapy in primary breast cancer. PATIENTS AND METHODS: The study was completed for 38 primary breast cancer patients (M0) who received pre-operative epirubicin and paclitaxel chemotherapy. Anemia was controlled by epoetin alfa and did not cause deviations from the planned chemotherapy schedule. RESULTS: There were no severe adverse events, cardiotoxicity or neutropenia. Patients with negative estrogen or progesterone receptors, or high KI-67 suffered more alopecia, while HER2 overexpressing patients had less severe nausea. CONCLUSION: This pre-operative chemotherapy regimen was well tolerated on the whole; side-effect profiles were correlated with tumor biological factors and also with response.

Circulating vascular endothelial growth factors and their soluble receptors in pre-invasive, invasive and recurrent cervical cancer.

AIM: To study the impact of circulating vascular endothelial growth factors (VEGF) -A, -C and -D and their soluble receptors VEGFR-1/-2 on disease invasion and progression in patients with pre-invasive (CIN), invasive (PCC) and recurrent (RCC) cervical cancer. PATIENTS AND METHODS: Blood samples were obtained from 125 women, including 50 cases of CIN, 51 of PCC and 24 of RCC, before treatment. Soluble (s) biomarker levels were determined by ELISA and tested for correlation with histopathological factors. RESULTS: With disease progression, sVEGF-A (p = 0.007) and sVEGFR-2 (p = 0.014) significantly increased, while sVEGF-D (p = 0.046) decreased. sVEGFR-2 levels were increased in node+ patients (p = 0.024) and in metastatic disease (p = 0.003). sVEGF-A values were higher in HPV+ cases (p = 0.019). In detecting disease invasiveness, sensitivity and specificity were 76% and 48% for sVEGF-A, 52% and 32% for sVEGF-D, 25% and 94% for sVEGF-C, 93% and 6% for sVEGFR-1 and 73% and 34% for sVEGFR-2, respectively. CONCLUSION: In cervical neoplasia, a switch from a lymphangiogenic phenotype towards a hemangiogenic phenotype occurs with disease invasion and progression. The sensitivity and specificity values, however, seem not convincing enough to establish these factors as clinical markers for disease invasiveness in cervical cancer.