Hyperechoic breast lesions: anatomopathological correlation and differential sonographic diagnosis

Abstract Hyperechoic lesions are not a frequent finding at breasts ultrasonography, and most of times are associated with benign pathologies that do not require further evaluation. However, some neoplasms such as invasive breast carcinomas and metastases may present with hyperechogenicity. Thus, the knowledge about differential diagnoses and identification of signs of lesion aggressiveness are of great relevance to avoid unnecessary procedures or underdiagnosis, and to support the correct clinical/surgical approach. On the basis of such concepts, the present essay describes and illustrates the main features of hyperechoic lesions at breast ultrasonography in different cases, with anatomopathological correlation.

Balloon-based adjuvant radiotherapy in breast cancer: comparison between 99mTc and HDR 192Ir

Abstract Objective: To perform a comparative dosimetric analysis, based on computer simulations, of temporary balloon implants with 99mTc and balloon brachytherapy with high-dose-rate (HDR) 192Ir, as boosts to radiotherapy. We hypothesized that the two techniques would produce equivalent doses under pre-established conditions of activity and exposure time. Materials and Methods: Simulations of implants with 99mTc-filled and HDR 192Ir-filled balloons were performed with the Siscodes/MCNP5, modeling in voxels a magnetic resonance imaging set related to a young female. Spatial dose rate distributions were determined. In the dosimetric analysis of the protocols, the exposure time and the level of activity required were specified. Results: The 99mTc balloon presented a weighted dose rate in the tumor bed of 0.428 cGy.h-1.mCi-1 and 0.190 cGyh-1.mCi-1 at the balloon surface and at 8-10 mm from the surface, respectively, compared with 0.499 and 0.150 cGyh-1.mCi-1, respectively, for the HDR 192Ir balloon. An exposure time of 24 hours was required for the 99mTc balloon to produce a boost of 10.14 Gy with 1.0 Ci, whereas only 24 minutes with 10.0 Ci segments were required for the HDR 192Ir balloon to produce a boost of 5.14 Gy at the same reference point, or 10.28 Gy in two 24-minutes fractions. Conclusion: Temporary 99mTc balloon implantation is an attractive option for adjuvant radiotherapy in breast cancer, because of its availability, economic viability, and similar dosimetry in comparison with the use of HDR 192Ir balloon implantation, which is the current standard in clinical practice.

The analgesic efficacy of ultrasound-guided transversus abdominis plane block (TAP Block) in adult patients : a meta-analysis

Introduction : Le bloc transverse de l'abdomen (bloc TAP, Transversus Abdominis Plane) échoguidé consiste en l'injection d'anesthésique local dans la paroi abdominale entre les muscles oblique interne et transverse de l'abdomen sous contrôle échographique. Ceci permet de bloquer l'innervation sensitive de la paroi antérolatérale de l'abdomen afin de soulager la douleur après des interventions chirurgicales. Auparavant, cette procédure reposait sur une technique dite « à l'aveugle » qui utilisait des repères anatomiques de surface. Depuis quelques années, cette technique est effectuée sous guidage échographique ; ainsi, il est possible de visualiser les structures anatomiques, l'aiguille et l'anesthésique local permettant ainsi une injection précise de l'anesthésique local à l'endroit désiré. Les précédentes méta- analyses sur le bloc TAP n'ont inclus qu'un nombre limité d'articles et n'ont pas examiné l'effet analgésique spécifique de la technique échoguidée. L'objectif de cette méta-analyse est donc de définir l'efficacité analgésique propre du bloc TAP échoguidé après des interventions abdominales chez une population adulte. Méthode : Cette méta-analyse a été effectuée selon les recommandations PRISMA. Une recherche a été effectuée dans les bases de donnée MEDLINE, Cochrane Central Register of Controlled Clinical Trials, Excerpta Medica database (EMBASE) et Cumulative Index to Nursing and Allied Health Literature (CINAHL). Le critère de jugement principal est la consommation intraveineuse de morphine cumulée à 6 h postopératoires, analysée selon le type de chirurgie (laparotomie, laparoscopie, césarienne), la technique anesthésique (anesthésie générale, anesthésie spinale avec/ou sans morphine intrathécale), le moment de l'injection (début ou fin de l'intervention), et la présence ou non d'une analgésie multimodale. Les critères de jugement secondaires sont, entre autres, les scores de douleur au repos et à l'effort à 6 h postopératoires (échelle analogique de 0 à 100), la présence ou non de nausées et vomissements postopératoires, la présence ou non de prurit, et le taux de complications de la technique. Résultats : Trente et une études randomisées contrôlées, incluant un total de 1611 adultes ont été incluses. Indépendamment du type de chirurgie, le bloc TAP échoguidé réduit la consommation de morphine à 6 h postopératoires (différence moyenne : 6 mg ; 95%IC : -7, -4 mg ; I =94% ; p<0.00001), sauf si les patients sont au bénéfice d'une anesthésie spinale avec morphine intrathécale. Le degré de réduction de consommation de morphine n'est pas influencé par le moment de l'injection (I2=0% ; p=0.72) ou la présence d'une analgésie multimodale (I2=73% ; p=0.05). Les scores de douleurs au repos et à l'effort à 6h postopératoire sont également réduits (différence moyenne au repos : -10 ; 95%IC : -15, -5 ; I =92% ; p=0.0002; différence moyenne en mouvement : -9 ; 95%IC : -14, -5 ; I2=58% ; p<0. 00001). Aucune différence n'a été retrouvée au niveau des nausées et vomissements postopératoires et du prurit. Deux complications mineures ont été identifiées (1 hématome, 1 réaction anaphylactoïde sur 1028 patients). Conclusions : Le bloc TAP échoguidé procure une analgésie postopératoire mineure et ne présente aucun bénéfice chez les patients ayant reçu de la morphine intrathécale. L'effet analgésique mineure est indépendant du moment de l'injection ou de la présence ou non d'une analgésie multimodale.

A new approach to the classification of mammographic masses and normal breast tissue

A new approach to mammographic mass detection is presented in this paper. Although different algorithms have been proposed for such a task, most of them are application dependent. In contrast, our approach makes use of a kindred topic in computer vision adapted to our particular problem. In this sense, we translate the eigenfaces approach for face detection/classification problems to a mass detection. Two different databases were used to show the robustness of the approach. The first one consisted on a set of 160 regions of interest (RoIs) extracted from the MIAS database, being 40 of them with confirmed masses and the rest normal tissue. The second set of RoIs was extracted from the DDSM database, and contained 196 RoIs containing masses and 392 with normal, but suspicious regions. Initial results demonstrate the feasibility of using such approach with performances comparable to other algorithms, with the advantage of being a more general, simple and cost-effective approach

Modeling and Classifying Breast Tissue Density in Mammograms

We present a new approach to model and classify breast parenchymal tissue. Given a mammogram, first, we will discover the distribution of the different tissue densities in an unsupervised manner, and second, we will use this tissue distribution to perform the classification. We achieve this using a classifier based on local descriptors and probabilistic Latent Semantic Analysis (pLSA), a generative model from the statistical text literature. We studied the influence of different descriptors like texture and SIFT features at the classification stage showing that textons outperform SIFT in all cases. Moreover we demonstrate that pLSA automatically extracts meaningful latent aspects generating a compact tissue representation based on their densities, useful for discriminating on mammogram classification. We show the results of tissue classification over the MIAS and DDSM datasets. We compare our method with approaches that classified these same datasets showing a better performance of our proposal

Identification of molecular subtypes and gene expression patterns of breast cancer analysing RNA-seq data

Breast cancer is the most common diagnosed cancer and the leading cause of cancer death among females worldwide. It is considered a highly heterogeneous disease and it must be classified into more homogeneous groups. Hence, the purpose of this study was to classify breast tumors based on variations in gene expression patterns derived from RNA sequencing by using different class discovery methods. 42 breast tumors paired-samples were sequenced by Illumine Genome Analyzer and the data was analyzed and prepared by TopHat2 and htseq-count. As reported previously, breast cancer could be grouped into five main groups known as basal epithelial-like group, HER2 group, normal breast-like group and two Luminal groups with a distinctive expression profile. Classifying breast tumor samples by using PAM50 method, the most common subtype was Luminal B and was significantly associated with ESR1 and ERBB2 high expression. Luminal A subtype had ESR1 and SLC39A6 significant high expression, whereas HER2 subtype had a high expression of ERBB2 and CNNE1 genes and low luminal epithelial gene expression. Basal-like and normal-like subtypes were associated with low expression of ESR1, PgR and HER2, and had significant high expression of cytokeratins 5 and 17. Our results were similar compared with TGCA breast cancer data results and with known studies related with breast cancer classification. Classifying breast tumors could add significant prognostic and predictive information to standard parameters, and moreover, identify marker genes for each subtype to find a better therapy for patients with breast cancer.

Core communication components along the cancer care process: the perspective of breast cancer patients

This study sought to assess the impact of health care professional (HCP) communication on breast cancer patients across the acute care process as perceived by patients. Methodological approach was based on eight focus groups conducted with a sample of patients (n ¼ 37) drawn from 15 Spanish Regions; thematic analysis was undertaken using the National Cancer Institute (NCI) framework of HCP communication as the theoretical basis. Relevant results of this study were the identification of four main communication components: (1) reassurance in coping with uncertainty after symptom detection and prompt access until confirmed diagnosis; (2) fostering involvement before delivering treatments, by anticipating information on practical and emotional illness-related issues; (3) guidance on the different therapeutic options, through use of clinical scenarios; and, (4) eliciting the feeling of emotional exhaustion after ending treatments and addressing the management of potential treatment-related effects. These communication-related components highlighted the need for a comprehensive approach in this area of cancer care

Synergism between dipyridamole and cisplatin in human breast cancer cells in vitro

Cisplatin is very effective in the treatment of metastatic breast cancer. However, the development of cellular resistance is a serious problem in cisplatin chemotherapy. In the present work, the effects of dipyridamole (DPM) on the cellular accumulation and cytotoxicity of cisplatin was studied in cisplatinsensitive (MDA/S) and cisplatinresistant (MDA/R) human breast cancer cells. In the presence of 30 µM DPM, the IC50 of cisplatin was reduced by 39% for both cell lines. Combination index analysis revealed that cisplatin and dipyridamole interact synergistically in MDA/R cells. In the MDA/S cells, the cellular accumulation of cisplatin increased by 57 ± 8% in the presence of 30 µM DPM. In the MDA/R cells, the cellular accumulation of cisplatin remained the same with or without 30 µM DPM. The results suggest that the enhancement of cisplatin cytotoxicity by DPM in MDA/S cells may be related to a DPM-induced increase in cisplatin accumulation, but the enhanced cytotoxicity in MDA/R cells employs a mechanism that does not involve an increase in the cellular accumulation of cisplatin.

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia

Rapid increase in incidence of breast ductal cancer in situ in Girona, Spain 1983-2007

Introduction: The aim of this study was to describe breast ductal cancer in situ (DCIS) incidence trends in women in the Girona province during a period of 25 years. The influence of age, use of mammography and implementation of the breast cancer screening programs was explored. Incidence of subsequent invasive breast cancers (IBC) and DCIS treatment was also considered. Materials and Methods: Cases diagnosed with primary pure DCIS (n=416) during 1983-2007 were extracted from the population-based Girona Cancer Registry. The estimated annual percent change was estimated using joinpoint analysis. Results: DCIS incidence showed a sharp rise until 1998, followed by a less marked upward trend. Among women aged 50-69 the increase was particularly important between 1992 and in 1996, reflecting the spread in mammography use. Conclusion: The upward trend of DCIS was mainly related to an increase in mammography use either opportunistic or as a result of screening implementation

Patson Approach versus the Standard Approach for increasing breast reconstruction rates in women undergoing mastectomy. A randomized, controlled, open-label clinical trial

Breast cancer is the most prevalent neoplasm among women in the majority of countries worldwide. Breast cancer treatment include mastectomy which is associated to strong impact in women. Breast reconstruction is an option for many women to re-establish their body image and also to decrease psychological impact. However, breast reconstruction rates are low and many factors are involved in not undergoing breast reconstruction. Patient involvement in the decision-making process increases breast reconstruction rates and is associated to higher satisfaction and less anxiety and depression symptoms. More physician-patient relation and more education in terms of breast reconstruction are needed to achieve our objective. A new approach of medical care, called Patson Approach, is created in order to meet our goal with more patient involvement, as well as, physician and psychological counsellingObjective: to increase breast reconstruction rates in women who are candidates for breast reconstruction after mastectomy and are included in the Patson Approach compared to women included in the Standard ApproachMethods: the study design will be a randomized, controlled, open-label clinical trial. 62 patients will be recruited during two years and randomly divided in two groups, 31 will be included in the Standard Approach and 31 will be included in the Patson Approach. Preoperative and postoperative appointments are established in order to do a follow-up of the patients and collect all the data

Online Ultrasound Measurements of Membrane Compaction

There are several filtration applications in the pulp and paper industry where the capacity and cost-effectiveness of processes are of importance. Ultrafiltration is used to clean process water. Ultrafiltration is a membrane process that separates a certain component or compound from a liquid stream. The pressure difference across the membrane sieves macromolecules smaller than 0.001-0.02 μm through the membrane. When optimizing the filtration process capacity, online information about the conditions of the membrane is needed. Fouling and compaction of the membrane both affect the capacity of the filtration process. In fouling a “cake” layer starts to build on the surface of the membrane. This layer blocks the molecules from sieving through the membrane thereby decreasing the yield of the process. In compaction of the membrane the structure is flattened out because of the high pressure applied. The higher pressure increases the capacity but may damage the structure of the membrane permanently. Information about the compaction is needed to effectively operate the filters. The objective of this study was to develop an accurate system for online monitoring of the condition of the membrane using ultrasound reflectometry. Measurements of ultrafiltration membrane compaction were made successfully utilizing ultrasound. The results were confirmed by permeate flux decline, measurements of compaction with a micrometer, mechanical compaction using a hydraulic piston and a scanning electron microscope (SEM). The scientific contribution of this thesis is to introduce a secondary ultrasound transducer to determine the speed of sound in the fluid used. The speed of sound is highly dependent on the temperature and pressure used in the filters. When the exact speed of sound is obtained by the reference transducer, the effect of temperature and pressure is eliminated. This speed is then used to calculate the distances with a higher accuracy. As the accuracy or the resolution of the ultrasound measurement is increased, the method can be applied to a higher amount of applications especially for processes where fouling layers are thinner because of smaller macromolecules. With the help of the transducer, membrane compaction of 13 μm was measured in the pressure of 5 bars. The results were verified with the permeate flux decline, which indicated that compaction had taken place. The measurements of compaction with a micrometer showed compaction of 23–26 μm. The results are in the same range and confirm the compaction. Mechanical compaction measurements were made using a hydraulic piston, and the result was the same 13 μm as obtained by applying the ultrasound time domain reflectometry (UTDR). A scanning electron microscope (SEM) was used to study the structure of the samples before and after the compaction.

Fibroblast Growth Factor 8 and its Receptors in The Growth and Angiogenesis of Experimental Breast Cancer . With Special Reference to Thrombospondin-1 as a Novel Target Gene for FGF-8

The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.