The biology of malignant breast tumors has an impact on the presentation in ultrasound: an analysis of 315 cases

BACKGROUND: The aim of this study was to evaluate the relation of some ultrasound morphological parameters to biological characteristics in breast carcinoma. METHODS: Ultrasound data from 315 breast masses were collected. We analyzed the ultrasound features of the tumors according to the ACR BI-RADS®-US classification system stratified by hormone receptor status, HER2 status, histology grade, tumor type (ductal versus lobular), triple-negativity, breast density, tumor size, lymph node involvement and patient’s age. RESULTS: We found a variety of ultrasound features that varied between the groups. Invasive lobular tumors were more likely to have an angulated margin (39% versus 22%, p = 0.040) and less likely to show posterior acoustic enhancement (3% versus 16%, p = 0.023) compared to invasive ductal carcinoma. G3 tumors were linked to a higher chance of posterior acoustic enhancement and less shadowing and the margin of G3 tumors was more often described as lobulated or microlobulated compared to G1/G2 tumors (67% versus 46%, p = 0.001). Tumors with an over-expression of HER2 exhibited a higher rate of architectural distortions in the surrounding tissue, but there were no differences regarding the other features. Hormone receptor negative tumors were more likely to exhibit a lobulated or microlobulated margin (67% versus 50%, p = 0.037) and less likely to have an echogenic halo (39% versus 64%, p = 0.001). Furthermore, the posterior acoustic feature was more often described as enhancement (33% versus 13%, p = 0.001) and less often as shadowing (20% versus 47%, p < 0.001) compared to hormone receptor positive tumors. CONCLUSION: Depending on their biological and clinical profile, breast cancers are more or less likely to exhibit the typical criteria for malignancy in ultrasound. Moreover, certain types of breast cancer tend to possess criteria that are usually associated with benign masses. False-negative diagnosis may result in serious consequences for the patient. For the sonographer it is essential to be well aware of potential variations in the ultrasound morphology of breast tumors, as described in this paper

Real-time ultrasound elastography in 180 axillary lymph nodes: elasticity distribution in healthy lymph nodes and prediction of breast cancer metastases

BACKGROUND: To determine the general appearance of normal axillary lymph nodes (LNs) in real-time tissue sonoelastography and to explore the method′s potential value in the prediction of LN metastases. METHODS: Axillary LNs in healthy probands (n=165) and metastatic LNs in breast cancer patients (n=15) were examined with palpation, B-mode ultrasound, Doppler and sonoelastography (assessment of the elasticity of the cortex and the medulla). The elasticity distributions were compared and sensitivity (SE) and specificity (SP) were calculated. In an exploratory analysis, positive and negative predictive values (PPV, NPV) were calculated based upon the estimated prevalence of LN metastases in different risk groups. RESULTS: In the elastogram, the LN cortex was significantly harder than the medulla in both healthy (p=0.004) and metastatic LNs (p=0.005). Comparing healthy and metastatic LNs, there was no difference in the elasticity distribution of the medulla (p=0.281), but we found a significantly harder cortex in metastatic LNs (p=0.006). The SE of clinical examination, B-mode ultrasound, Doppler ultrasound and sonoelastography was revealed to be 13.3%, 40.0%, 14.3% and 60.0%, respectively, and SP was 88.4%, 96.8%, 95.6% and 79.6%, respectively. The highest SE was achieved by the disjunctive combination of B-mode and elastographic features (cortex >3mm in B-mode or blue cortex in the elastogram, SE=73.3%). The highest SP was achieved by the conjunctive combination of B-mode ultrasound and elastography (cortex >3mm in B-mode and blue cortex in the elastogram, SP=99.3%). CONCLUSIONS: Sonoelastography is a feasible method to visualize the elasticity distribution of LNs. Moreover, sonoelastography is capable of detecting elasticity differences between the cortex and medulla, and between metastatic and healthy LNs. Therefore, sonoelastography yields additional information about axillary LN status and can improve the PPV, although this method is still experimental

Robustness of positional specification by the Hedgehog morphogen gradient

AbstractSpatial gradients of Hedgehog signalling play a central role in many patterning events during animal development, regulating cell fate determination and tissue growth in a variety of tissues and developmental stages. Experimental evidence suggests that many of the proteins responsible for regulating Hedgehog signalling and transport are themselves targets of Hedgehog signalling, leading to multiple levels of feedback within the system. We use mathematical modelling to analyse how these overlapping feedbacks combine to regulate patterning and potentially enhance robustness in the Drosophila wing imaginal disc. Our results predict that the regulation of Hedgehog transport and stability by glypicans, as well as multiple overlapping feedbacks in the Hedgehog response network, can combine to enhance the robustness of positional specification against variability in Hedgehog levels. We also discuss potential trade-offs between robustness and additional features of the Hedgehog gradient, such as signalling range and size regulation

The Automated Breast Volume Scanner (ABVS): initial experiences in lesion detection compared with conventional handheld B-mode ultrasound: a pilot study of 50 cases

The idea of an automated whole breast ultrasound was developed three decades ago. We present our initial experiences with the latest technical advance in this technique, the automated breast volume scanner (ABVS) ACUSON S2000™. Volume data sets were collected from 50 patients and a database containing 23 women with no detectable lesions in conventional ultrasound (BI-RADS®-US 1), 13 women with clearly benign lesions (BI-RADS®-US 2), and 14 women with known breast cancer (BI-RADS®-US 5) was created. An independent examiner evaluated the ABVS data on a separate workstation without any prior knowledge of the patients’ histories. The diagnostic accuracy for the experimental ABVS was 66.0% (95% confidence interval [CI]: 52.9–79.1). The independent examiner detected all breast cancers in the volume data resulting in a calculated sensitivity of 100% in the described setting (95% CI: 73.2%–100%). After the ABVS examination, there were a high number of requests for second-look ultrasounds in 47% (95% CI: 30.9–63.5) of the healthy women (with either a clearly benign lesion or no breast lesions at all in conventional handheld ultrasound). Therefore, the specificity remained at 52.8% (95% CI: 35.7–69.2). When comparing the concordance of the ABVS with the gold standard (conventional handheld ultrasound), Cohen’s Kappa value as an estimation of the inter-rater reliability was κ = 0.37, indicating fair agreement. In conclusion, the ABVS must still be regarded as an experimental technique for breast ultrasound, which definitely needs to undergo further evaluation studies

Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling

Wnt signalling plays essential roles during embryonic development and is known to be mis-regulated in human disease. There are many molecular mechanisms that ensure tight regulation of Wnt activity. One such regulator is the heparan-sulfate-specific 6-O-endosulfatase Sulf1. Sulf1 acts extracellularly to modify the structure of heparan sulfate chains to affect the bio-availability of Wnt ligands. Sulf1 could, therefore, influence the formation of Wnt signalling complexes to modulate the activation of both canonical and non-canonical pathways. In this study, we use well-established assays in Xenopus to investigate the ability of Sulf1 to modify canonical and non-canonical Wnt signalling. In addition, we model the ability of Sulf1 to influence morphogen gradients using fluorescently tagged Wnt ligands in ectodermal explants. We show that Sulf1 overexpression has ligand-specific effects on Wnt signalling: it affects membrane accumulation and extracellular levels of tagged Wnt8a and Wnt11b ligands differently, and inhibits the activity of canonical Wnt8a but enhances the activity of non-canonical Wnt11b

Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid

The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog and identified its downstream target as stromal GLI1+ mesenchymal stem cell-like cells. In vivo genetic impairment of Hedgehog signaling induced significant loss of choroidal mast cells, as well as an altered inflammatory response and exacerbated visual function defects after retinal damage. Our studies reveal the cellular and molecular landscape of adult RPE/choroid and uncover a Hedgehog-regulated choroidal immunomodulatory signaling circuit. These results open new avenues for the study and treatment of retinal vascular diseases and choroid-related inflammatory blinding disorders.Funding for this study was provided by National Institutes of Health grants EY08538 and GM34107 (E. Rodriguez-Boulan); EY027038 (R.F. Mullins); 1R21CA224391-01A1 (J.H. Zippin); and 1R01CA194547, 1U24CA210989, and P50CA211024 (O. Elemento); National Cancer Institute grant R01CA192176 and cancer center support grant P30 CA008748-48 (A.L. Joyner); Comunidad Autónoma de Madrid grant 2017-T1/BMD-5247 (I. Benedicto); Agencia Nacional Argentina de Promoción Cient´ıfica y Tecnológica grant PICT 2014-3687 and Fundación Sales (G.A. Rabinovich); a Pew Latin American Fellowship (G.L. Lehmann); Calder Research Scholar Award Vitiligo/Pigment Cell Disorders (J.H. Zippin); Starr Foundation Tri-Institutional Stem Cell Initiative award 2013-028; NYSTEM contract C32596GG; and Research to Prevent Blindness and Dyson Foundation departmental grants. The CNIC is supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

The cost-effectiveness of follow-up strategies after cancer treatment: a systematic literature review

Introduction: The cost of treatment and follow-up of cancer patients in the UK is substantial. In a budget-constrained system such as the NHS, it is necessary to consider the cost-effectiveness of the range of management strategies at different points on cancer patients' care pathways to ensure that they provide adequate value for money. Sources of data: We conducted a systematic literature review to explore the cost-effectiveness of follow-up strategies of patients previously treated for cancer with the aim of informing UK policy. All papers that were considered to be economic evaluations in the subject areas described above were extracted. Areas of agreement: The existing literature suggests that intensive follow-up of patients with colorectal disease is likely to be cost-effective, but the opposite holds for breast cancer. Areas of controversy: Interventions and strategies for follow-up in cancer patients were variable across type of cancer and setting. Drawing general conclusions about the cost-effectiveness of these interventions/strategies is difficult. Growing points: The search identified 2036 references but applying inclusion/exclusion criteria a total of 44 articles were included in the analysis. Breast cancer was the most common (n = 11) cancer type followed by colorectal (n = 10) cancer. In general, there were relatively few studies of cost-effectiveness of follow-up that could influence UK guidance. Where there was evidence, in the most part, NICE guidance broadly reflected this evidence. Areas timely to develop research: In terms of future research around the timing, frequency and composition of follow-ups, this is dependent on the type of cancer being considered. Nevertheless, across most cancers, the possibility of remote follow-up (or testing) by health professionals other than hospital consultants in other settings appears to warrant further work