Aneurysmal bone cystic lesions: value of genomic studies.

Aneurysmal bone cystic (ABC) lesions can be primary or secondary (to a trauma or a pre-existing benign or malignant tumour). Specific translocations of the USP6 gene are reported in about 70% of primary but never in secondary ABC lesions. We report two cases of ABC lesions in which imbalanced genomic aberrations were detected at initial presentation and showed complex clonal evolution. These demonstrative observations strengthen the guidelines regarding the diagnostic approach when an ABC is suggested by imaging. Biopsy is mandatory including genomic analysis. When a primary ABC is not clearly proven by the initial biopsy, an extensive curettage should be performed, with pathological examination of all removed tissue in order to exclude a secondary ABC. It also illustrates the added value of genomic analyses in the setting of an ABC lesion: complex clonal aberrations argues for a lesion secondary to a malignant proliferation whereas USP6 rearrangement allows the diagnosis of primary ABC.

Texture analysis on MR images helps predicting non-response to NAC in breast cancer.

BACKGROUND: To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI. METHODS: Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC. RESULTS: A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction. CONCLUSION: Pre-NAC texture and kinetic parameters help predicting non-benefit to NAC. Further testing including larger groups of patients with different tumor subtypes is needed to improve the generalization properties and validate the performance of the predictive model.

A pilot study about speech changes after partial Tucker's laryngectomy: the reduction of regressive voicing assimilation.

Partial frontolateral laryngectomy (PL) is performed to remove larynx tumor while preserving its main functions. So far, the speech changes induced by difficulties of voicing and the alterations to the vocal tract due to PL have been seldom addressed. The goal of our study was to make an acoustic analysis of regressive voicing assimilation (RVA) among patients after PL and to study the relationship with rates of speech. A retrospective study was conducted from January to April 2013. 11 subjects treated by partial frontolateral laryngectomy, and ten healthy subjects were included. Functional recordings of voice were analyzed and compared. For assimilation sequences we found a significant modification of voicing ratio in healthy subjects (p < 0.05) and PL patient at accelerated speaking rate only (p < 0.05). The vowel duration is significantly modified only for healthy subjects. For all subjects (PL patients and healthy) the duration of C1 consonant was not significantly modified. Our results highlight the presence of RVA in healthy subjects, but also in PL patients in the rapid speaking mode.

[Dynamic palatography: Diagnostic tool for dysfunc­tional swallowing? Feasibility study].

Objective: Dysfunctional swallowing may cause transverse occlusal disorders. The speech re-education of dysfunctional swallowing aims to correct or prevent the recurrence of occlu­sal disorders. The main objective was to test the dynamic palato­graphy as a diagnosis and quantification tool of the dysfunctional swallowing. Material and methods: The study was prospective and descriptive. Twelve average 23.5 years old women with a clinical dysfunctional swallowing have been included between January and May 2014. None was aware of presenting an atypical swallowing or dento-facial dysmorphism of class II. The dynamic palatography device measured the pressure force of the language on the palate during the lingual rest, swallowing saliva and water. Parameters measured were the duration and magnitude of support of the tongue on the palate. Results: Dynamic palatography showed a trend to predominant anterior contact during rest position (25%), and lower position of the language with little contact during swallo­wing of saliva and water. Discussion: Palatography results are consistent with the clinical diagnostic criteria of atypical swallo­wing. Our palatography tool has the advantage of being unobtrusive in the mouth compared to other pre existing systems. This device should be tested on larger patient popu­la­tions and could enable monitore atypical swallowing rehabili­ta­tion efficiency. The palatography could complete the swallo­wing assessment and be a monitoring and rehabilitation tool in real time.

[Study of tongue pressure on the hard palate during exercises of swallowing rehabilitation]. / Etude de la pression de la langue sur le palais osseux au cours desexercices de rééducation de la déglutition.

INTRODUCTION: The exercises performed during the reeducation of swallowing seek to improve forces of propulsion of the bolus and airway protection during the course of swallowing. The objective of this study was to objectify the effect of pronunciation praxis of posterior phonemes /aka/ and /akra/, and swallowing maneuvers (super-supraglottic swallow with or without superimposed effort swallowing effort) on the time of the oral swallowing. MATERIALS AND METHODS: Four healthy volunteers participated in the experiment. They are called "experts" because they have a good knowledge of physiology and rehabilitation of swallowing. The dynamic palatography setup measured continuously the different pressures from the tongue on the hard palate through three force sensors arranged in a sagittal plane during the implementation of articulatory and swallowing tasks. RESULTS: Articulatory praxis created significant pressure on the posterior sensor for 2 of the 4 subjects. All the swallowing maneuvers increased the contact pressure and the contact duration compared to the control swallowing for the anterior and posterior pressure sensor. A large inter-individual variability was found. CONCLUSION: The complexity of instruction, the inter-individual variability in their performance, and the non-invasive nature of the instrument make the dynamic palatography a potentially useful tool in routine practice of swallowing reeducation.

Genomic grade adds prognostic value in invasive lobular carcinoma.

BACKGROUND: The prognostic value of histologic grade (HG) in invasive lobular carcinoma (ILC) remains uncertain, and most ILC tumors are graded as HG2. Genomic grade (GG) is a 97-gene signature that improves the prognostic value of HG. This study evaluates whether GG may overcome the limitations of HG in ILC. METHODS: Gene expression data were generated from frozen tumor samples, and GG calculated according to the expression of 97 genes. The prognostic value of GG was assessed in a stratified Cox regression model for invasive disease-free survival (IDFS) and overall survival (OS). RESULTS: A total of 166 patients were classified by GG. HG classified 33 (20%) tumors as HG1, 120 (73%) as HG2 and 12 (7%) as HG3. GG classified 106 (64%) tumors as GG low (GG1), 29 (17%) as GG high (GG3) and 31 (19%) as equivocal (cases not classified as GG1 or GG3). The median follow-up time was 6.5 years. In multivariate analyses, GG was associated with IDFS [HR(GG3 vs GG1) 5.6 (2.1-15.3); P < 0.001] and OS [HR(GG3 vs GG1) 7.2, 95% CI (1.6-32.2); P = 0.01]. CONCLUSIONS: GG outperformed HG in ILC and added prognostic value to classic clinicopathologic variables, including nodal status.

Optimizing specimen collection and laboratory procedures reduces the non-diagnostic rate for endoscopic ultrasound-guided fine-needle aspiration of solid lesions of the pancreas.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a routine technique to assess solid pancreatic lesions. The aim of this study was to analyse the effect of optimizing laboratory procedures for specimen preparation on the rate and accuracy of the procedure. METHODS: All EUS-FNAs of solid pancreatic lesions performed during the year 2000 (Period 1) and from May 2003 to May 2004 (Period 2) were analysed. During Period 1, one experienced gastroenterologist performed all EUS-FNAs, making direct smears and retrieving small fragments if present on the smear for histology. In Period 2, two endoscopists performed the EUS-FNAs and all the material was emptied into a vial containing a fixative. Slide preparation was carried out in the pathology laboratory: one slide was processed using cytocentrifugation and cell blocks were made from left-over material. Neither period utilized rapid on-site evaluation. RESULTS: During the two periods, 67 and 102 FNAs were analysed and showed significantly different (P < 0.001) non-diagnostic rates of 22.8% and 4.2%, respectively. The increased diagnostic yield can be explained by the modified laboratory procedures and to a lesser extent by the increased experience of the gastroenterologists. Sensitivity, specificity, PPV, NPV and accuracy in the second time period were, respectively, 90.6%, 100%, 100%, 81.8% and 93.4%, not significantly different from the first time period. CONCLUSION: This study shows that accurate EUS-FNA results may be obtained with a low non-diagnostic rate comparable to those reported for rapid on-site evaluation by optimizing laboratory specimen processing in a setting of solid pancreatic lesions.

Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.

OBJECTIVE: Rituximab displays therapeutic benefits in the treatment of patients with rheumatoid arthritis (RA) resistant to tumor necrosis factor (TNF) blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. We undertook this study to investigate the global molecular effects of rituximab in synovial biopsy samples obtained from anti-TNF-resistant RA patients before and after administration of the drug. METHODS: Paired synovial biopsy samples were obtained from the affected knee of anti-TNF-resistant RA patients before (time 0) and 12 weeks after (time 12) initiation of rituximab therapy. Total RNA was extracted, labeled according to standard Affymetrix procedures, and hybridized on GeneChip HGU133 Plus 2.0 slides. Immunohistochemistry and quantitative real-time reverse transcriptase-polymerase chain reaction experiments were performed to confirm the differential expression of selected transcripts. RESULTS: According to Student's paired t-tests, 549 of 54,675 investigated probe sets were differentially expressed between time 0 and time 12. Pathway analysis revealed that genes down-regulated between time 0 and time 12 were significantly enriched in immunoglobulin genes and genes involved in chemotaxis, leukocyte activation, and immune responses (Gene Ontology annotations). In contrast, genes up-regulated between time 0 and time 12 were significantly enriched in transcripts involved in cell development (Gene Ontology annotation) and wound healing (Gene Set Enrichment Analysis). At baseline, higher synovial expression of immunoglobulin genes was associated with response to therapy. CONCLUSION: Rituximab displays unique effects on global gene expression profiles in the synovial tissue of RA patients. These observations open new perspectives in the understanding of the biologic effects of the drug and in the selection of patients likely to benefit from this therapy.

Influence of phonetic context on the dysphonic event: contribution of new methodologies for the analysis of pathological voice.

Widely studied in terms of perception, acoustics or aerodynamics, dysphonia stays nevertheless a speech phenomenon, closely related to the phonetic composition of the message conveyed by the voice. In this paper, we present a series of three works with the aim to understand the implications of the phonetic manifestation of dysphonia. Our first study proposes a new approach to the perceptual analysis of dysphonia (the phonetic labeling), which principle is to listen and evaluate each phoneme in a sentence separately. This study confirms the hypothesis of Laver that the dysphonia is not a constant noise added to the speech signal, but a discontinuous phenomenon, occurring on certain phonemes, based on the phonetic context. However, the burden of executing the task has led us to look to the techniques of automatic speaker recognition (ASR) to automate the procedure. With the collaboration of the LIA, we have developed a system for automatic classification of dysphonia from the techniques of ASR. This is the subject of our second study. The first results obtained with this system suggest that the unvoiced consonants show predominant performance in the task of automatic classification of dysphonia. This result is surprising since it is often assumed that dysphonia occurs only on laryngeal vibration. We started looking for explanations of this phenomenon and we present our assumptions and experiences in the third work we present.

Guidelines of clinical practice for the management of swallowing disorders and recent dysphonia in the context of the COVID-19 pandemic.

Procedures putting healthcare workers in close contact with the airway are particularly at risk of contamination by the SARS-Cov-2 virus, especially when exposed to sputum, coughing, or a tracheostomy. In the current pandemic phase, all patients should be considered as potentially infected. Thus, the level of precaution recommended for the caregivers depends more on the type of procedure than on the patient's proved or suspected COVID-19 status. Procedures that are particularly at high risk of contamination are clinical and flexible endoscopic pharyngo-laryngological evaluation, and probably also video fluoroscopic swallowing exams. Voice rehabilitation should not be considered urgent at this time. Therefore, recommendations presented here mainly concern the management of swallowing disorders, which can sometimes be dangerous for the patient, and recent dysphonia. In cases where they are considered possible and useful, teleconsultations should be preferred to face-to-face assessments or rehabilitation sessions. The latter must be maintained only in few selected situations, after team discussions or in accordance with the guidelines provided by health authorities.

Development of an animal experimental model to study the effects of levonorgestrel on the human endometrium.

BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery. METHODS: Proliferative human endometrium was subcutaneously grafted in two groups of SCID mice that received, 2 days before, a subcutaneous estradiol (E(2)) pellet and, for half of them, an additional implant of levonorgestrel (LNG). Mice were sacrificed 1, 2, 3 or 4 weeks after endometrial implantation and grafts were histologically analysed. Proliferation, steroid hormone receptors, blood vessels and stromal decidualization in both groups (E(2) and LNG) were immunohistologically evaluated and compared with proliferative endometrium and endometrium from women with an LNG intrauterine device. RESULTS: Grafts presented normal morphological endometrial characteristics. The expression of progesterone receptors was significantly decreased in glands and stroma of the LNG group as compared with the E(2) group at all times. A significant decrease was also observed in the stromal expression of estrogen receptor-alpha in the LNG group. At 4 weeks, the mean cross-sectional area of vessels was significantly higher after LNG treatment. CONCLUSIONS: These morphological and immunohistochemical characteristics are similar to those observed in women treated with local LNG. This mouse model might facilitate further investigations needed to understand the mechanisms responsible for the breakthrough bleeding frequently observed in progestin users.

Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation.

BACKGROUND: Menstruation is associated with a striking increase in matrix metalloproteinase (MMP) activity. However, it is still unknown whether the level of MMP activity correlates with the amount of menstrual bleeding. METHODS: We used histochemistry to investigate the degradation of the extracellular matrix (ECM), and immunohistochemical labelling and zymographic analysis to determine the level of expression and activity of MMP-2 and -9, and of their tissue inhibitors (TIMPs) -1, -2 and -3, in endometria sampled during menstruation in 14 women experiencing excessive menstrual bleeding and in 10 women successfully treated for menorrhagia by thermal ablation of the endometrium. RESULTS: After thermal ablation, regenerated menstrual endometria showed reduced areas of collagen fibre lysis and increased content of TIMP-1 and TIMP-2 compared with endometria from non-treated menorrhagic women. Surprisingly, treated endometria contained more latent gelatinase A (proMMP-2) but a lower proportion of the active form of gelatinase B (MMP-9) than non-treated endometria. CONCLUSIONS: These results suggest that ECM degradation is decreased at menstruation in the endometrium regenerated after thermal ablation, mostly because of an increased TIMP expression. This represents the first molecular explanation for the decreased amount of menstrual bleeding.

Mixed origin of neovascularization of human endometrial grafts in immunodeficient mouse models.

BACKGROUND: In vivo mouse models have been developed to study the physiology of normal and pathologic endometrium. Although angiogenesis is known to play an important role in endometrial physiology and pathology, the origin of neovasculature in xenografts remains controversial. The aim of this study was to assess the origin of the neovasculature of endometrial grafts in different mouse models. METHODS: Human proliferative endometrium (n = 19 women) was grafted s.c. in two immunodeficient mouse strains: nude (n = 8) and severely compromised immunodeficient (SCID; n = 20). Mice were also treated with estradiol, progesterone or levonorgestrel. Fluorescence in-situ hybridization using a centromeric human chromosome X probe, immunohistochemistry (von Willebrand factor and collagen IV) and lectin perfusion were performed to identify the origin of the vessels. RESULTS: More than 90% of vessels within xenografts were of human origin 4 weeks after implantation. Some vessels (9.67 +/- 2.01%) were successively stained by human or mouse specific markers, suggesting the presence of chimeric vessels exhibiting a succession of human and murine portions. No difference in staining was observed between the two strains of mouse or different hormone treatments. Furthermore, erythrocytes were found inside human vessels, confirming their functionality. CONCLUSION: This article shows that human endometrial grafts retain their own vessels, which connect to the murine vasculature coming from the host tissue and become functional.

Fused micro-computed tomography (µCT) and histological images of bone specimens.

OBJECTIVES: To describe a stepwise process to obtain fused images from micro-computed tomography (µCT) and histological images of bone specimens. MATERIAL AND METHODS: Four surgically resected human femoral heads from four patients who had total hip replacement were imaged at a spatial resolution of 12-microns by using µCT. Histological sections of four focal bone lesions including bone cyst in osteoarthritis (n=2) and subchondral bone plate fracture in osteonecrosis (n=2) were prepared and digitized. µCT images were reformatted and adjusted to match the histological images using a landmark-based visual co-registration. Fused µCT and histological images were displayed in a cine-loop video mode with a gradual transition from one image to the other. RESULTS: µCT images of the four focal bone lesions could be successfully fused with the corresponding histological images with a near perfect match of the bone trabeculae. CONCLUSION: We present a stepwise process to obtain fused images from histological and reformatted µCT images of human femoral heads.

[Juvenille papillomatosis]. / Papillomatose juvénile mammaire.

The authors report a patient with juvenile papillomatosis of the breast presenting with a palpable mass and illustrate the correlation between mammographic, sonographic and pathologic features.

Quality of pathology reporting is crucial for cancer care and registration: a baseline assessment for breast cancers diagnosed in Belgium in 2008.

OBJECTIVES: Given the crucial role of pathology reporting in the management of breast cancers, we aimed to investigate the quality and variability of breast cancer pathology reporting in Belgium. MATERIALS AND METHODS: Detailed information on non-molecular and molecular parameters was retrieved from the pathology protocols available at the Belgian Cancer Registry for 10,007 breast cancers diagnosed in Belgium in 2008. RESULTS: Substantial underreporting was shown for several clinically relevant non-molecular parameters, such as lymphovascular invasion. High-volume laboratories performed only slightly better than others, and analyses at the individual laboratory level showed clear inter-laboratory variability in reporting for all volume categories. Information on ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for HER2 IHC. For cases with different specimens analysed, discordance between these specimens was highest for HER2, followed by PR. For HER2, results obtained from different laboratories were even less concordant. In addition, inter-laboratory differences were noted in the used ER/PR scoring systems, the proportion of ER-/PR+ cases, and the relation between histological grade and ER/PR positivity. Data on Ki67 were only available for 43.8% of the investigated cases, and showed inconsistent use of cut-off values. CONCLUSION: Breast pathology reporting in Belgium in 2008 was suboptimal and showed considerable inter-laboratory variability. Synoptic reporting has been proposed as a facilitator towards increased reporting quality and harmonization, but the lack of aligned informatics remains a major hurdle in its concrete implementation.

Eosinophilic fasciitis: typical abnormalities, variants and differential diagnosis of fasciae abnormalities using MR imaging.

Eosinophilic fasciitis is a rare condition. It is generally limited to the distal parts of the arms and legs. MRI is the ideal imaging modality for diagnosing and monitoring this condition. MRI findings typically evidence only fascial involvement but on a less regular basis signal abnormalities may be observed in neighboring muscle tissue and hypodermic fat. Differential diagnosis of eosinophilic fasciitis by MRI requires the exclusion of several other superficial and deep soft tissue disorders.

The place of extensive surgery in locoregional recurrence and limited metastatic disease of breast cancer: preliminary results.

UNLABELLED: The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence. MATERIAL AND METHODS: Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable. RESULTS: The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival. CONCLUSION: Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent.