[Management of complicated Barrett's esophagus. Observational study carried out in a regional hospital]. / Prise en charge de l'œsophage de Barrett compliqué. Étude observationnelle réalisée dans un centre hospitalier régional.

The incidence of Barrett's esophagus, complication of gastroesophageal reflux disease, is rising in western countries. It is the same for esophageal adenocarcinoma, of which it is the main contributing factor. This retrospective study seeks to report the incidence of these pathologies observed in a regional hospital center and to describe their management. In 5 years, 354 Barrett's esophagus are detected and 34 of them are complicated by high-grade dysplasia or adenocarcinoma. Endoscopic resection is performed in 24 of these patients. The histological analysis of which leads to the conclusion of adenocarcinoma in 20 patients and high-grade dysplasia in the 14 others. The complications of endoscopic and surgical resections are detailed. Their frequency and severity remain low, comparable to data in the literature.

L'incidence de l'œsophage de Barrett, complication du reflux gastro-œsophagien, est en croissance dans les pays occidentaux. Il en est de même de l'adénocarcinome œsophagien dont il est le principal facteur favorisant. Cette étude rétrospective s'attache à rapporter l'incidence de ces pathologies, observées dans un centre hospitalier régional, et à détailler leur prise en charge. En 5 ans, 354 œsophages de Barrett sont détectés et 34 d'entre eux sont compliqués de dysplasie de haut grade ou d'adénocarcinome. Une résection endoscopique est réalisée chez 24 de ces malades. Les analyses histologiques permettent de conclure à un adénocarcinome chez 20 malades et une dysplasie de haut grade chez les 14 restants. Les complications des résections endoscopiques et chirurgicales sont détaillées. Leur fréquence et leur gravité restent faibles, comparables aux données de la littérature.

CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis.

BACKGROUND: The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them. METHODS: We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES). RESULTS: 997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported. CONCLUSIONS: Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT. CLINICAL TRIAL REGISTRATION: ID number NCT01193075.

[What's wrong with "development of isolating mechanisms" (and its special case in form of "reinforcement")?].

Examined are the conceptual grounds of the "reinforcement" model that play an important role in explanatory schemes of the theory of evolution. According to the current views, reinforcement (of obstacles for crossing under natural selection when there occurs a repeated contact with hybridization between two substantially divergent forms, up to the level where started hybridization is terminated and the forms become unable to cross) should be a common or even frequent phenomenon. In fact, reinforcement turns out to be a rare event needed to be specially searched for, all such events are dubious, etc. Here, empirical data on reinforcement pro and contra are analyzed, using mostly ornithological (and some other zoological) materials. It is shown that in most cases where the theory predicts reinforcement to occur, it does not happen. On the contrary, something quite opposite is observed--selection for non-crossing enhancement does not stop up the leaks in gene pools of the forms that are due to their hybridization within the zone of a repeated contact, but instead the stable hybrid zone is established which serve as a conduit for gene exchange between the forms. Through hybridization, those forms can adopt strange genes, remaining, at that, their isolation at the level of separate species. This is achieved through the system of self-non-self recognition in population system of both forms being in contact. Within the zone of a repeated contact, conditions are usually such that individuals repeatedly make mistakes forming mixed pairs and producing hybrids, i.e., at the level of individuals, self-non-self recognition is often inefficient, especially at the range edges, in zone of repeated contact and such. Efficient recognition, that ensures species separateness even under conditions of continuing hybridization, takes place upon inclusion of individuals of different origin--phenotypically 'pure' ones, hybrids, and backcrosses--into spatio-ethologic population structure of both forms, upon acquisition of territories by established groups, their inclusion in flocks and other intra-population associations of resident individuals. At that, groups of both forms predominantly incorporate their 'own' ('pure') phenotypes and reject 'strange' ones, including hybrids of intermediate phenotype. If the forms have attained the species level of separateness, hybrids do not form their own stable groups, but try to individually inset themselves into the habitation of both parents, which turns out to be not so successful as compared with phenotypically 'pure' individuals of the given form. Thereby, hybrids happen to be directly excluded from the population system of both forms even if hybridization goes on and produces them in sufficient quantity while hybrids and backcrosses themselves are not inferior to 'pure' individuals either in survivorship or reproductive success (those ones who became residents have occupied a territory and are reproducing). It is shown that usual examples of reinforcement are not only sparse but could be explained differently. Particularly, 'splitting up' of a population system which gives rise to two forms of different ecology with following strengthening/enhancement of the divergence through sexual selection is better explained by our model of self-non-self recognition than by reinforcement. Relying on this concept, the conclusion is drawn that the model of non-crossing 'reinforcement' in zones of a repeated contact with hybridization is not supported by the data, as well as the model of character displacement that follows from it. Apparently, the reasons behind its popularity consist in conformity with the 'ideology' of a more general theory that is agreed upon by most researchers, and corresponds, in whole, to known facts (in this case, the theory of modern evolutionary synthesis).

[Management and follow-up of a consecutive series of 411 surgically treated breast cancer patients]. / Prise en charge et suivi d'une série consécutive de 411 patientes opérées pour cancer du sein.

This study reports a consecutive serie of 427 breast neoplasms (411 patients) diagnosed and treated in our department between 1994 and 2004. Patients' records were prospectively collected including personnal medical history and the major elements of the diagnostic and the therapeutic protocol applied. 12 patients (3%) had to be excluded due to incomplete follow-up data. With a median follow-up of 8 years, a 4.5% loco-regional relapse rate is noted while 11% of patients recurred at distant sites and 9% died of their disease progression. These statistics are comparable to those published by prominant breast cancer centers. Amongst the 16% of deaths (67/411 Pts), 54% are due to breast cancer progression. The results are discussed with the aim to upgrade the diagnostic and the therapeutic protocols offered to our patients.

Altered plasma serine and 1-deoxydihydroceramide profiles are associated with diabetic neuropathy in type 2 diabetes and obesity.

Recent studies suggest that the accumulation of atypical, 1-deoxysphingolipids that lack the C1 hydroxyl group may be associated with diabetic neuropathy (DN). We hypothesized that specific plasma 1-deoxysphingolipids associate with DN severity, and that alterations in plasma serine and alanine associate with 1-deoxysphingolipid elevation in patients with type 2 diabetes (T2D). We examined individual 1-deoxysphingolipid species using LC/MS/MS in plasma samples from 75 individuals including lean controls (LC, n = 19), those with obesity (n = 19), obesity with T2D without DN (ob/T2D, n = 18), and obesity with T2D with DN (Ob/T2D/DN, n = 19). We observed a step wise increase in 1-deoxydihydroceramides across these four groups (spearman correlation coefficient r = 0.41, p = 0.0002). Mean total concentrations of 1-deoxydihydroceramides, and most individual 1-deoxydihydroceramide species, were higher in ob/T2D/DN versus LC group (8.939 vs. 5.195 pmol/100 µL for total 1-deoxydihydroceramides p = 0.005). No significant differences in 1-deoxydihydroceramides were observed between the ob/T2D and ob/T2D/DN groups. l-alanine was higher and l-serine lower in ob/T2D/DN versus LC groups (326.2 vs. 248.0 µM, p = 0.0086 and 70.2 vs. 89.8 µM, p = 0.0110), consistent with a potential contribution of these changes to the observed 1-deoxysphingolipids profiles. 1-deoxydihydroceramides correlated inversely with leg intraepidermal nerve fiber density (CC -0.40, p = 0.003). These findings indicate that 1-deoxydihydroceramides may be important biomarkers and/or mediators of DN.

Mid-anaphase arrest in S. cerevisiae cells eliminated for the function of Cin8 and dynein.

S. cerevisiae anaphase spindle elongation is accomplished by the overlapping function of dynein and the kinesin-5 motor proteins, Cin8 and Kip1. Cin8 and dynein are synthetically lethal, yet the arrest phenotypes of cells eliminated for their function had not been identified. We found that at a non-permissive temperature, dyn1 Delta cells that carry a temperature-sensitive cin8 - 3 mutation arrest at mid-anaphase with a unique phenotype, which we named TAN (two microtubule asters in one nucleus). These cells enter anaphase, but fail to proceed through the slow phase of anaphase B. At a permissive temperature, dyn1 Delta, cin8 - 3 or dyn1 Delta cin8 - 3 cells exhibit perturbed spindle midzone morphologies, with dyn1Delta cin8 - 3 anaphase spindles also being profoundly bent and nonrigid. Sorbitol, which has been suggested to stabilize microtubules, corrects these defects and suppresses the TAN phenotype. We conclude that dynein and Cin8 cooperate in anaphase midzone organization and influence microtubule dynamics, thus enabling progression through the slow phase of anaphase B.

[Neuroendocrine tumors of the appendix]. / Tumeurs neuroendocrines appendiculaires: à propos d'un cas, de l'histologie à la thérapeutique.

An 19-year-old woman was admitted for acute appendicitis. The histological study of the appendix revealed a tubular variant of endocrine carcinoma of the appendix. Neuroendocrine tumors ("NETs") of the appendix are rare tumors which are usually detected incidentally, affecting 0.3% to 0.9% of appendectomies. Depending on their size, but also on some other factors, including histologic type, these tumors will require specific treatment; sometimes appendectomy will not be sufficient.

[Clinical case of the month. Liver transplantation for hepatic epithelioid hemangioendothelioma]. / Transplantation hépatique pour un hémangio-endothéliome épithélioïde du foie.

The epithelioid hemangioendothelioma is a rare malignant vascular lesion that may occur within the liver. In the hepatic multifocal and bilobar forms, liver transplantation is indicated as the curative management. In this case report, the authors describe the diagnosis and the management of a 52-year-old woman who was diagnosed with hepatic epithelioid hemangioendothelioma and who underwent successful liver transplantation.

Impact of immunohistochemical markers, CK5/6 and E-cadherin on diagnostic agreement in non-invasive proliferative breast lesions.

AIMS: To assess the impact of cytokeratin (CK) 5/6 and E-cadherin immunohistochemistry on diagnostic agreement of non-invasive proliferative breast lesions. METHODS AND RESULTS: Twenty pathologists classified 105 cases of non-invasive proliferative breast lesions into 10 diagnostic categories. One haematoxylin and eosin (H&E) slide of each case was analysed on a first round and one H&E slide with corresponding CK5/6 and E-cadherin immunohistochemistry was analysed on a second round. Interobserver reproducibility for category-specific and management-specific lesions was measured on each round. CK5/6 and E-cadherin had little impact on diagnostic agreement, which remained moderate between the first and second rounds (overall kappa coefficients of 0.47 and 0.53, respectively, P = NS). Levels of agreement slightly improved for lesions with specific CK5/6 and E-cadherin immunoprofiles (usual ductal hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, non-high-grade ductal carcinoma in situ), but the differences observed were not statistically significant. However, diagnostic agreement improved when lesions were grouped according to their management category (overall kappa coefficients of 0.58 and 0.66 in the first and second rounds, respectively). CONCLUSIONS: CK5/6 and E-cadherin immunohistochemistry has little impact on interobserver reproducibility for non-invasive breast lesions. Diagnostic agreement can, however, be improved by grouping lesions in management categories.

[Validation of the sentinel lymph node biopsy in breast cancer]. / Validation de la technique de biopsie du ganglion sentinelle dans le cancer du sein.

PURPOSE: Assessment of our experience and validation of the sentinel lymph node biopsy technique in breast cancer stage T0-T2N0M0 surgery. METHODS: Identification and biopsy of the sentinel lymph node by the radio colloid method in a consecutive series of 205 patients undergoing surgery for breast cancer stage T0-T2N0M0 between October 1998 and January 2007, initially in association with a complete axillary lymph node dissection (learning curve), later in an elective way. Prospective recording of the data and analysis with an average follow-up of 50 months (3 to 102 months). RESULTS: Biopsy rate of the sentinel lymph node of 90%, false negative rate of the method 2.5%, axillary recurrence rate 0%. CONCLUSION: We confirm in this series that the sentinel lymph node biopsy technique is a reliable approach in our experience for the evaluation of the axillary lymph node status in breast cancer stage T0-T2N0M0.

[Urbanization mechanisms in bird species: population systems transformations or adaptations at the individual level?].

The present research deals with urbanization of wild bird and mammal species. Forms and mechanisms of population steadiness in the urban landscape have been examined. The urbanization process turned out to be a directed change of the population system forming de novo in the urbolandscape leading to a sustainable organization peculiar for the particular environment. The population organization of different types in urbolandscape is found to provide its stability under conditions of directed and fast changes accompanied with instability and heterogenous structure of habitats. It is shown that the same type of population organization meets the corresponding demands among different species settling in the urban environment. Its features are "openness" and "flowage" of the groups, far order of settlement levels and other units of population system, constant movements of the individuals between the groups as a respond to the signals of urboenvironment significant changes. The "urban" variant of the population system organization turns out to be opposite to that of the same species in the non-urban habitats. After formation of the urban types by the species and successful developing of the town, the urban population becomes separated from the maternal local population and begins to exist independently in the urban landscape. The variety of adaptation aberrations in ecology, behavior, and mode of life of urban birds is the population system stability function in the urban landscape and is not a results of individual selection. It is shown that the urbanization process of the species goes firstly on the population level being the system structure transformation developed by the species towards the most stable state in the town (city) territory. Only after the appearance of stable urban population, the urban individuals show the rapid growth of different changes in ecology, behavior, mode of life that was traditionally described by naturalists as species adaptation to the city conditions. The key features of urban population stability/instability are described. Their application to closely related species allows us to distinguish potential urbanists from instable and vulnerable species that could be soon pushed out of the city. The application of corresponding criteria to the urban populations of such species constituting one guild allows us to predict if their developing in the given town would be successful or unsuccessful. The latter is very important since close species are, as a rule, ecologically indistinguishable in the urbanized landscapes. So one can not predict successful/unsuccessful urbanization taking into account the differences in the range of habitats, breeding success, and other external features.

[Ileum intussusception in an adult: a case report]. / Invagination iléo-iléale chez un adulte.

Intussusception in adults is a rare cause of intestinal obstruction and is usually secondary to some lesion in the gastrointestinal tract. We report a case of intestinal obstruction due to ileo-ileal intussusception, an inflammatory fibroid polyp formed the leading edge of the intussusceptum, which is a rare polypoidal lesion of the gastrointestinal tract.

[A bilateral dysgerminoma: a rare presentation of the Swyer syndrome]. / Le cas clinique du mois: un dysgerminome bilatéral: une présentation rare du syndrome de Swyer.

Swyer syndrome is a pure gonad dysgenesis associating 46 XY karyotype, primary amenorrhea, presence of female internal genital tract and bilateral streak gonads in a phenotypic female. The diagnosis is usually made at adolescence when the primary amenorrhea is investigated. We report the case of a 25-year-old XY woman who developed a bilateral dysgerminoma from undifferentiated gonads.

Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies.

We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].

Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type.

A formalin-fixation and paraffin-processing resistant epitope of Ki-67 cell proliferation-associated antigen was immunohistochemically detected by the MIB-1 monoclonal antibody (Immunotech, Marseille, France) in 25 routinely processed cervical biopsies showing normal squamous epithelium or squamous metaplasia and in 65 cervical intraepithelial lesions (SILs) (44 low grade and 21 high grade SILs) with human papillomavirus (HPV) infection. Expression of Ki-67 antigen was exclusively confined to the parabasal and basal layers of normal and metaplastic epithelium. There was no significant difference of Ki-67 antigen immunostaining between normal cervical biopsies and cases of squamous metaplasia. In SIL specimens, the staining was markedly increased in the parabasal and basal layers and Ki-67-positive cells were also distributed in the intermediate (low grade SIL) or all layers of epithelium (high grade SIL). Statistically significant differences for the density of Ki-67 antigen-labeled cells, which were assessed with an image analysis system, were found in comparisons between normal or metaplastic epithelium and SILs (P < .001) and between low grade SILs and high grade SILs (P < .001). In our series of SILs, HPV 16/18 and 31/33/35/novel types, which were found in both low grade and high grade SILs, were significantly associated with higher densities of Ki-67 antigen-positive cells than HPV 6/11 types that were found exclusively in low grade SILs. There was no significant difference found between the densities of Ki-67 antigen-labeled cells in HPV 16/18-positive and HPV 31/33/35/novel types-positive tissues in our series of SILs taken as a whole or when segregating SILs into low grade and high grade.

Assessment of tumor angiogenesis in invasive breast carcinomas: absence of correlation with prognosis and pathological factors.

Different retrospective studies have shown that microvessel counting (MVC) is an independent prognostic marker for clinical outcome in breast cancer. The aim of this study was to evaluate the prognostic value of MVC alone or in association with classical clinicopathological parameters, as well as the reproducibility of the technique. We analyzed a retrospective series of 216 cases of breast carcinoma. Tissue sections were stained for Factor-VIII-related antigen. Microvessel quantification was performed at x400 magnification in the three most vascular areas of the tumors (hot spots). Mean and highest values were studied. Furthermore, a semi-quantitative evaluation of MVC was performed by use of an image-analysis system. The effect of multiple factors on survival was tested under a Cox multivariate proportional hazards model. In ten cases, a study of the reproducibility was done by evaluating MVC in different sections of the same block and in different blocks of a same tumor. There was no association between MVC (determined at a microscopic level or by image analysis) and overall survival or relapse-free survival. No association was found with tumor size, tumor grade, and lymph-node status. The study of reproducibility showed a very high intra-tumoral variation of MVC. The intra-individual coefficient of variation (CV) varied between 20 and 80%. This study did not show any significant correlation between angiogenesis, as assessed by MVC, and relapse-free survival or overall survival in infiltrating breast carcinomas. The low reproducibility of the MVC for the same tumors suggests that this technique must still be optimized before routine application.

[HER2 gene amplification assay: is CISH an alternative to FISH?]. / Recherche de l'amplification du gène HER2: la CISH est-elle une alternative à la technique FISH?

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

[Anatomo-pathologic examination of breast cancer: a prerequisite for optimal therapeutic choice]. / L'examen anatomo-pathologique d'un cancer du sein: un prérequis pour un bon choix thérapeutique.

Breast cancer represents the most frequent cause of cancer deaths in women in Belgium. At the time of diagnosis, the clinician must get the most accurate information on the anatomic features and staging in order to choose the most appropriate therapy. The pathologist play a central role in providing these data. The paper presents a summary of a standardized and reproducible procedure, which is currently used by the pathologists, according to the international recommendations. It consists of several successive steps, from macroscopic examination and dissection of the surgical specimen to histological analysis. The pathologist's protocol contains all the required data and emphasizes the parameters with the most significant prognostic value, such as the histological type and grade and the lymph node status.

[Prognostic evaluation of human solid tumors by immunohistology]. / Evaluation pronostique des tumeurs solides humaines par immunohistologie.

The aim of this project is to evaluate the interest of new tumor markers in the most frequent solid tumors (breast, colon, prostatic cancers, ...). For each of these tumors, potential prognostic markers have been selected according to the literature and an immunohistologic technique has been developed to analyse them. We will first discuss the role of pathology in oncology, then briefly describe the analyzed markers and finally give information about a Web site (URL: http:/(/)www.ebm. lib.ulg.ac.be/index.htm) created to help clinicians exploit the laboratory results.