[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.

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.

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.

[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.

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.

[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.

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.

[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.

Sinonasal involvement as a rare extraintestinal manifestation of Crohn's disease.

Crohn's disease is a chronic idiopathic slowly developing transmural inflammation of the digestive system. It usually involves the small intestine and/or the area around the anus but can also affect the entire gastrointestinal tract anywhere from the mouth to the anus. Extra intestinal manifestations occur frequently and multiple organ systems may be affected: the skin, joints, spine, eyes, liver and bile ducts. In contrast, nasal manifestations are extremely rare and only a few cases have been reported up to date in the worldwide literature. The authors report two cases with nasal manifestations concomitant to intestinal Crohn's disease and go over the relevant literature on such an association.

[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.

[Registration of various classes of otoacoustic emission in definition of acoustic sensitivity in different forms of neurosensory hypoacusis]. / Registratsiia razlichnykh klassov otoakusticheskoi émissii v opredelenii slukhovoi chuvstvitel'nosti pri razlichnykh formakh sensonevral'noi tugoukhosti.

To establish correlations between parameters of otoacoustic emission and audiometric thresholds, we have examined 30 ears (28 patients) with high-frequency neurosensory hypoacusis. The analysis of the findings was made in microstructural frequency resolution. It was discovered that peaks of spontaneous otoacoustic emission correspond by frequency range to minimal thresholds of audibility in all the cases. Minimal values of audibility thresholds correlate also by frequency with maximal values of amplitudes of the response signal of delayed evoked otoacoustic emission with good sigmal/noise in all the examinees as well. 23 ears demonstrated 'mirrow' correlation of pure-tone audiogram with DP-gram - a rise in behavioral thresholds corresponds to amplitude-lowering response signals in frequency range 3-6 kHz.

Evidence of a limited contribution of feto-maternal interactions to trophoblast differentiation along the invasive pathway.

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane and proliferate to form aggregates called trophoblast cell columns (TCCs). They subsequently invade the decidua and differentiate into interstitial and endovascular trophoblasts. The influence of the decidua on EVT differentiation is controversial. We therefore compared the pattern of trophoblast differentiation marker expression in viable intrauterine and tubal pregnancies, as decidual cell markers (prolactin [PRL] and insulin-like growth factor binding Protein-1 [IGFBP1]) were only expressed in endometrial implantation sites. Extravillous trophoblast differentiation in anchoring villi from uterine and ectopic pregnancies exhibited a comparable phenotypical switch: alpha6 integrin subunit, E-cadherin, EGF receptor, Ki 67 and connexin 40 were localized in the proximal part of the TCC, while alpha5beta1 and alpha1 integrins, c-erb B2, hPL and HLA-G were expressed by invasive cytotrophoblasts. The cyclin-dependent kinase inhibitors p16 and p57 were mainly detected in invasive cytotrophoblasts some distance from the columns. However, the TCC was markedly longer in tubal pregnancy than in intrauterine pregnancy. These findings suggest that the decidua is not necessary to trigger EVT invasion, but that it is likely to limit the extent of the TCC and to accelerate the onset of EVT migration.

[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.

En bloc excision of nonpalpable breast lesions using the advanced breast biopsy instrumentation system: an alternative to needle guided surgery?

This study was prospectively conducted to evaluate the clinical potential of the advanced breast biopsy instrumentation (ABBI) system as an alternative to needle localization and open surgery in the management of nonpalpable breast lesions (NPBL). One hundred and eighty-six consecutive patients were referred for management of NPBL. Thirty-six underwent an ABBI procedure, offered as a first step before possible surgery for lesions which would in any case have required complete excision. The 18 patients with a malignant ABBI biopsy underwent re-excision of the biopsy site and axillary dissection was carried out in cases of infiltrating carcinoma. The other 150 patients underwent image-guided needle biopsy. Following these procedures, 60/150 (40%) patients underwent needle-guided surgery. Finally, 96/186 (51%) patients required complete excision. A total of 43 benign lesions and 53 carcinomas were confirmed. Thirty-six out of 96 (38%) excisions were obtained with the ABBI system; 17/43 (40%) benign lesions and 11/53 (21%) carcinomas were completely removed with the ABBI system. Out of 9 malignant specimens with a pathological size less than 10 mm, 5/9 (55%) had tumor-free margins and in 8/9 (89%) no residual disease was found at re-excision. The preliminary results of this study suggest that, in selected cases, en bloc excision using the ABBI procedure could be an alternative to conventional surgery.