Epiphysenfugenverletzungen der distalen Tibia. Sinnvolle Mehrinformation durch die MRT? [Epiphyseal injuries of the distal tibia. Does MRI provide useful additional information?]

Plain film radiography often underestimates the extent of injury in children with epiphyseal fracture. Especially Salter-Harris V fractures (crush fracture of the epiphyseal plate) are often primarily not detected. MRI of the ankle was performed in 10 children aged 9-17 (mean 14) years with suspected epiphyseal injury using 1.0-T Magnetom Expert. The fractures were classified according to the Salter-Harris-Rang-Odgen classification and compared with the results of plain radiography. In one case MRI could exclude epiphyseal injury; in four cases the MRI findings changed the therapeutic management. The visualisation of the fracture in three orthogonal planes and the possibility of detection of cartilage and ligamentous injury in MR imaging makes this method superior to conventional radiography and CT. With respect to radiation exposure MRI instead of CT should be used for the diagnosis of epiphyseal injuries in children.

Axillary Sentinel Lymph Node Biopsy for Breast Cancer and Melanoma Patients after Previous Axillary Surgery: A Systematic Review

Objective: Sentinel lymph node biopsy (SLNB) is a validated staging technique for breast carcinoma. Some women are exposed to have a second SLNB due to breast cancer recurrence or a second neoplasia (breast or other). Due to modi- fied anatomy, it has been claimed that previous axillary surgery represents a contra-indication to SLNB. Our objective was to analyse the literature to assess if a second SLNB is to be recommended or not. Methods: For the present study, we performed a review of all published data during the last 10 years on patients with previous axilla surgery and second SLNB. Results: Our analysis shows that second SLNB is feasible in 70%. Extra-axillary SNs rate (31%) was higher after radical lymph node dissection (ALND) (60% - 84%) than after SLNB alone (14% - 65%). Follow-up and com- plementary ALND following negative and positive second SLNB shows that it is a reliable procedure. Conclusion: The review of literature confirms that SLNB is feasible after previous axillary dissection. Triple technique for SN mapping is the best examination to highlight modified lymphatic anatomy and shows definitively where SLNB must be per- formed. Surgery may be more demanding as patients may have more frequently extra-axillary SN only, like internal mammary nodes. ALND can be avoided when second SLNB harvests negative SNs. These conclusions should however be taken with caution because of the heterogeneity of publications regarding SLNB and surgical technique.

Accelerated Microstructure Imaging via Convex Optimization (AMICO) from diffusion MRI data.

Microstructure imaging from diffusion magnetic resonance (MR) data represents an invaluable tool to study non-invasively the morphology of tissues and to provide a biological insight into their microstructural organization. In recent years, a variety of biophysical models have been proposed to associate particular patterns observed in the measured signal with specific microstructural properties of the neuronal tissue, such as axon diameter and fiber density. Despite very appealing results showing that the estimated microstructure indices agree very well with histological examinations, existing techniques require computationally very expensive non-linear procedures to fit the models to the data which, in practice, demand the use of powerful computer clusters for large-scale applications. In this work, we present a general framework for Accelerated Microstructure Imaging via Convex Optimization (AMICO) and show how to re-formulate this class of techniques as convenient linear systems which, then, can be efficiently solved using very fast algorithms. We demonstrate this linearization of the fitting problem for two specific models, i.e. ActiveAx and NODDI, providing a very attractive alternative for parameter estimation in those techniques; however, the AMICO framework is general and flexible enough to work also for the wider space of microstructure imaging methods. Results demonstrate that AMICO represents an effective means to accelerate the fit of existing techniques drastically (up to four orders of magnitude faster) while preserving accuracy and precision in the estimated model parameters (correlation above 0.9). We believe that the availability of such ultrafast algorithms will help to accelerate the spread of microstructure imaging to larger cohorts of patients and to study a wider spectrum of neurological disorders.

Mutations of mitochondrial DNA as potential biomarkers in breast cancer.

BACKGROUND: Alterations of mitochondrial DNA (mtDNA) have been found in cancer patients, therefore informative mtDNA mutations could serve as biomarkers for the disease. MATERIALS AND METHODS: The two hypervariable regions HVR1 and HVR2 in the D-Loop region were sequenced in ten paired tissue and plasma samples from breast cancer patients. RESULTS: MtDNA mutations were found in all patients' samples, suggesting a 100% detection rate. Examining germline mtDNA mutations, a total of 85 mutations in the D-loop region were found; 31 of these mutations were detected in both tissues and matched plasma samples, the other 54 germline mtDNA mutations were found only in the plasma samples. Regarding somatic mtDNA mutations, a total of 42 mutations in the D-loop region were found in breast cancer tissues. CONCLUSION: Somatic mtDNA mutations in the D-loop region were detected in breast cancer tissues but not in the matched plasma samples, suggesting that more sensitive methods will be needed for such detection to be of clinical utility.

Endocytic and secretory traffic in Arabidopsis merge in the trans-Golgi network/early endosome, an independent and highly dynamic organelle.

Plants constantly adjust their repertoire of plasma membrane proteins that mediates transduction of environmental and developmental signals as well as transport of ions, nutrients, and hormones. The importance of regulated secretory and endocytic trafficking is becoming increasingly clear; however, our knowledge of the compartments and molecular machinery involved is still fragmentary. We used immunogold electron microscopy and confocal laser scanning microscopy to trace the route of cargo molecules, including the BRASSINOSTEROID INSENSITIVE1 receptor and the REQUIRES HIGH BORON1 boron exporter, throughout the plant endomembrane system. Our results provide evidence that both endocytic and secretory cargo pass through the trans-Golgi network/early endosome (TGN/EE) and demonstrate that cargo in late endosomes/multivesicular bodies is destined for vacuolar degradation. Moreover, using spinning disc microscopy, we show that TGN/EEs move independently and are only transiently associated with an individual Golgi stack.

Clinical review--breast adenoid cystic carcinoma.

OBJECTIVES: To review the published literature on the diagnosis and management of adenoid cystic carcinoma (ACC) of the breast.¦MATERIALS AND METHODS: Papers were identified by searching PubMed using the terms « adenoid cystic carcinoma » and « breast ». Additional papers were identified by reviewing references of relevant articles.¦RESULTS: ACC of the breast is a rare tumour comprising less than 0.1% of breast malignancies. Its cellular origin in the breast remains unclear. The histological characteristics of ACC in the breast are similar to those of ACC of the salivary glands. However the prognosis of ACC of the breast is better than that of other localizations with prolonged survival. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients.¦CONCLUSIONS: ACC of the breast has a favourable prognosis. An accurate diagnosis and appropriate treatment are therefore important.

Bacterial biofilms and capsular contracture in patients with breast implants.

BACKGROUND: It has been hypothesized that bacterial biofilms on breast implants may cause chronic inflammation leading to capsular contracture. The association between bacterial biofilms of removed implants and capsular contracture was investigated. METHODS: Breast implants explanted between 2006 and 2010 at five participating centres for plastic and reconstructive surgery were investigated by sonication. Bacterial cultures derived from sonication were correlated with patient, surgical and implant characteristics, and the degree of capsular contracture. RESULTS: The study included 121 breast implants from 84 patients, of which 119 originated from women and two from men undergoing gender reassignment. Some 50 breast prostheses were implanted for reconstruction, 48 for aesthetic reasons and 23 implants were used as temporary expander devices. The median indwelling time was 4·0 (range 0·1-32) years for permanent implants and 3 (range 1-6) months for temporary devices. Excluding nine implants with clinical signs of infection, sonication cultures were positive in 40 (45 per cent) of 89 permanent implants and in 12 (52 per cent) of 23 temporary devices. Analysis of permanent implants showed that a positive bacterial culture after sonication correlated with the degree of capsular contracture: Baker I, two of 11 implants; Baker II, two of ten; Baker III, nine of 23; and Baker IV, 27 of 45 (P < 0·001). The most frequent organisms were Propionibacterium acnes (25 implants) and coagulase-negative staphylococci (21). CONCLUSION: Sonication cultures correlated with the degree of capsular contracture, indicating the potential causative role of bacterial biofilms in the pathogenesis of capsular contracture. Registration number: NCT01138891 (http://www.clinicaltrials.gov).

MRI monitoring of focal cerebral ischemia in peroxisome proliferator-activated receptor (PPAR)-deficient mice.

Peroxisome proliferator-activated receptors (PPARs) are a potential target for neuroprotection in focal ischemic stroke. These nuclear receptors have major effects in lipid metabolism, but they are also involved in inflammatory processes. Three PPAR isotypes have been identified: alpha, beta (or delta) and gamma. The development of PPAR transgenic mice offers a promising tool for prospective therapeutic studies. This study used MRI to assess the role of PPARalpha and PPARbeta in the development of stroke. Permanent middle cerebral artery occlusion induced focal ischemia in wild-type, PPARalpha-null mice and PPARbeta-null mice. T(2)-weighted MRI was performed with a 7 T MRI scan on day 0, 1, 3, 7 and 14 to monitor lesion growth in the various genotypes. General Linear Model statistical analysis found a significant difference in lesion volume between wild-type and PPAR-null mice for both alpha and beta isotypes. These data validate high-resolution MRI for monitoring cerebral ischemic lesions, and confirm the neuroprotective role of PPARalpha and PPARbeta in the brain.

Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial

RESUME BUT Cette étude a été menée sur le suivi de patients traités pour un glioblastome nouvellement diagnostiqué. Son objectif a été de déterminer l'impact des séquences de perfusion et de diffusion en imagerie par résonance magnétique (IRM). Un intérêt particulier a été porté au potentiel de ces nouvelles techniques d'imagerie dans l'anticipation de la progression de la maladie. En effet, l'intervalle de temps libre de progression est une mesure alternative de pronostic fréquemment utilisée. MATERIEL ET METHODE L'étude a porté sur 41 patients participant à un essai clinique de phase II de traitement par temozolomide. Leur suivi radiologique a comporté un examen IRM dans les 21 à 28 jours après radiochimiothérapie et tous les 2 mois par la suite. L'évaluation des images s'est faite sur la base de l'évaluation de l'effet de masse ainsi que de la mesure de la taille de la lésion sur les images suivantes : T1 avec produit de contraste, T2, diffusion, perfusion. Afin de déterminer la date de progression de la maladie, les critères classiques de variation de taille adjoints aux critères cliniques habituels ont été utilisés. RESULAT 311 examens IRM ont été revus. Au moment de la progression (32 patients), une régression multivariée selon Cox a permis de déterminer deux paramètres de survie : diamètre maximal en T1 (p>0.02) et variation de taille en T2 (p<0.05). L'impact de la perfusion et de la diffusion n'a pas été démontré de manière statistiquement significative. CONCLUSION Les techniques de perfusion et de diffusion ne peuvent pas être utilisées pour anticiper la progression tumorale. Alors que la prise de décision au niveau thérapeutique est critique au moment de la progression de la maladie, l'IRM classique en T1 et en T2 reste la méthode d'imagerie de choix. De manière plus spécifique, une prise de contraste en T1 supérieure à 3 cm dans son plus grand diamètre associée à un hypersignal T2 en augmentation forment un marqueur de mauvais pronostic.

Dynamic, auxin-responsive plasma membrane-to-nucleus movement of Arabidopsis BRX.

In Arabidopsis, interplay between nuclear auxin perception and trans-cellular polar auxin transport determines the transcriptional auxin response. In brevis radix (brx) mutants, this response is impaired, probably indirectly because of disturbed crosstalk between the auxin and brassinosteroid pathways. Here we provide evidence that BRX protein is plasma membrane-associated, but translocates to the nucleus upon auxin treatment to modulate cellular growth, possibly in conjunction with NGATHA class B3 domain-type transcription factors. Application of the polar auxin transport inhibitor naphthalene phthalamic acid (NPA) resulted in increased BRX abundance at the plasma membrane. Thus, nuclear translocation of BRX could depend on cellular auxin concentration or on auxin flux. Supporting this idea, NPA treatment of wild-type roots phenocopied the brx root meristem phenotype. Moreover, BRX is constitutively turned over by the proteasome pathway in the nucleus. However, a stabilized C-terminal BRX fragment significantly rescued the brx root growth phenotype and triggered a hypocotyl gain-of-function phenotype, similar to strong overexpressors of full length BRX. Therefore, although BRX activity is required in the nucleus, excess activity interferes with normal development. Finally, similar to the PIN-FORMED 1 (PIN1) auxin efflux carrier, BRX is polarly localized in vascular cells and subject to endocytic recycling. Expression of BRX under control of the PIN1 promoter fully rescued the brx short root phenotype, suggesting that the two genes act in the same tissues. Collectively, our results suggest that BRX might provide a contextual readout to synchronize cellular growth with the auxin concentration gradient across the root tip.

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

BACKGROUND: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. PATIENTS AND METHODS: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. RESULTS: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). CONCLUSIONS: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. CLINICALTRIALSGOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.

Breast cancer and melanoma cell line identification by FTIR imaging after formalin-fixation and paraffin-embedding.

Over the past few decades, Fourier transform infrared (FTIR) spectroscopy coupled to microscopy has been recognized as an emerging and potentially powerful tool in cancer research and diagnosis. For this purpose, histological analyses performed by pathologists are mostly carried out on biopsied tissue that undergoes the formalin-fixation and paraffin-embedding (FFPE) procedure. This processing method ensures an optimal and permanent preservation of the samples, making FFPE-archived tissue an extremely valuable source for retrospective studies. Nevertheless, as highlighted by previous studies, this fixation procedure significantly changes the principal constituents of cells, resulting in important effects on their infrared (IR) spectrum. Despite the chemical and spectral influence of FFPE processing, some studies demonstrate that FTIR imaging allows precise identification of the different cell types present in biopsied tissue, indicating that the FFPE process preserves spectral differences between distinct cell types. In this study, we investigated whether this is also the case for closely related cell lines. We analyzed spectra from 8 cancerous epithelial cell lines: 4 breast cancer cell lines and 4 melanoma cell lines. For each cell line, we harvested cells at subconfluence and divided them into two sets. We first tested the "original" capability of FTIR imaging to identify these closely related cell lines on cells just dried on BaF2 slides. We then repeated the test after submitting the cells to the FFPE procedure. Our results show that the IR spectra of FFPE processed cancerous cell lines undergo small but significant changes due to the treatment. The spectral modifications were interpreted as a potential decrease in the phospholipid content and protein denaturation, in line with the scientific literature on the topic. Nevertheless, unsupervised analyses showed that spectral proximities and distances between closely related cell lines were mostly, but not entirely, conserved after FFPE processing. Finally, PLS-DA statistical analyses highlighted that closely related cell lines are still successfully identified and efficiently distinguished by FTIR spectroscopy after FFPE treatment. This last result paves the way towards identification and characterization of cellular subtypes on FFPE tissue sections by FTIR imaging, indicating that this analysis technique could become a potential useful tool in cancer research.