Inducible CXCL12/CXCR4-dependent extramedullary hematopoietic niches in the adrenal gland.

Adult hematopoietic Stem and Progenitor Cells (HSPCs) reside in the bone marrow hematopoietic niche, which regulates HSPC quiescence, self-renewal, and commitment in a demand-adapted manner. While the complex bone marrow niche is responsible for adult hematopoiesis, evidence exists for simpler, albeit functional and more accessible, extramedullary hematopoietic niches. Inspired by the anecdotal description of retroperitoneal hematopoietic masses occurring at higher frequency upon hormonal dysregulation within the adrenal gland, we hypothesized that the adult adrenal gland could be induced into a hematopoietic supportive environment in a systematic manner, thus revealing mechanisms underlying de novo niche formation in the adult. Here we show that upon splenectomy and hormonal stimulation, the adult adrenal gland of mice can be induced to recruit and host functional HSPCs, capable of serial transplantation, and that this phenomenon is associated with de novo formation of platelet-derived growth factor receptor α (PDGFRα) expressing stromal nodules. We further show in CXCL12-GFP reporter mice that adrenal glands contain a stromal population reminiscent of the CXCL12-Abundant Reticular (CAR) cells which compose the bone marrow HSPC niche. Mechanistically, HSPC homing to hormonally-induced adrenal glands was found dependent on the CXCR4/CXCL12 axis. Mirroring our findings in mice, we found reticular CXCL12+ cells co-expressing master niche-regulator FOXC1 in primary samples from human adrenal myelolipomas, a benign tumor composed of adipose and hematopoietic tissue. Our findings reignite long-standing questions regarding hormonal regulation of hematopoiesis and provide a novel model to facilitate the study of adult-specific inducible hematopoietic niches which may pave the way to therapeutic applications.

[Towards bariatric surgery : taking your time preserves you from loosing your time]. / Préparation à la chirurgie bariatrique : lorsque prendre du temps n'est pas en perdre.

Obesity has become a worldwide public health concern. Bariatric surgery is nowadays the most effective treatment to lose weight and control somatic comorbidities of this disease. However, a careful preparation of the patients undergoing bariatric surgery seems mandatory, despite the existence of a feeling of emergency that is often shared by the therapeutic team, and thus difficult to handle. In this context, the importance to address psychological issues such as patients' representation of their body while they will be confronted to a major physical transformation cannot be over-emphasized. Taking time is crucial to create a therapeutic context that raises the patients' awareness of their underlying psychological functioning.

Le traitement de l'obésité est devenu une problématique de santé publique mondiale. La chirurgie bariatrique est actuellement le moyen le plus efficace pour perdre du poids et contrôler les comorbidités somatiques de cette maladie. Toutefois, une préparation approfondie des patients semble incontournable malgré une impulsion d'urgence souvent partagée par les soignants qui peinent à refréner cette dynamique. L'importance d'anticiper le vécu psychique du patient, face à un corps qui va rapidement se trouver confronté à une modification de son schéma et de son image corporels, nous semble indispensable. Prendre du temps est essentiel afin d'aménager un espace permettant au patient de conscientiser les changements à venir et de pouvoir les affronter sereinement pour le reste de sa vie.

[Novelties 2016 in pediatrics]. / Pédiatrie.

Nutrition is central in pediatric care : essential for growth and development, it plays also a role in the prevention of many diseases.Even if breastfeeding is highly recommended, its implementation may be difficult in particular for premature and ill newborns. The creation of a specific unit for breastfeeding support in neonatology allows to help mothers willing to nurse and to improve the rate of breastfeeding for these vulnerable infants.Eating disorders represent an important challenge for patient care. Early detection and rapid management of anorexia is essential for the prognosis. This article describes the challenges and the practical process underlying the development of a practical guideline to manage children and adolescents hospitalized for anorexia.

La nutrition est un thème central en pédiatrie : essentielle pour la croissance et le développement de l'enfant, elle joue également un rôle dans la prévention de nombreuses maladies.Bien que fortement recommandée, la mise en place de l'allaitement peut être difficile en particulier chez les nouveau-nés prématurés ou malades. La création d'une unité de soutien à l'allaitement en néonatologie a permis d'offrir un soutien aux mères souhaitant allaiter et d'améliorer le taux de lactation. Les troubles du comportement alimentaire représentent un important challenge de prise en charge. Une détection et une prise en charge rapide de l'anorexie sont essentielles pour le pronostic. Cet article décrit les enjeux et le processus parcouru pour élaborer un guide de prise en charge des enfants et adolescent(e)s hospitalisé(e)s pour une anorexie.

[Why is the management of patients suffering from mental anorexia regarded as difficult?]. / Pourquoi l'anorexie mentate est-elle considérée comme une maladie difficile à soigner?

Management of patients suffering from mental anorexia (AM) is often regarded as particularly difficult. Some difficulties are inherent to the disease itself and to the interactions with the care providers; others are linked to the family context, sociological and organizational factors. Delayed access to specialized care is favored by denial of the disease, a diagnostic criterion of AM which echoes the valorization of thinness extolled by today's society. Considering AM as an intrinsic cause of difficulties for the medical teams could induce withdrawal of care providers or even the Institutions. Nevertheless it should be kept in mind that AM is the psychiatric disease with the highest mortality rate. Considering the particular complexity of management of AM, it is of special importance to develop specialized units to take care of these patients.

Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group.

The clinicopathologic and immunohistochemical features of 63 pleomorphic liposarcomas are presented. There were 35 men and 28 women (median age 63 years; range 18-93 years). Tumor size ranged from 2 to 23 cm (median 10 cm). Tumor locations included lower extremity (36.5%), especially the thigh (28.5%), limb girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and internal trunk (20.5%). A total of 75% were deep seated and/or extracompartmental. Histologically, lesions show a varying combination of lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma-like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in 51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to 124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48; 19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%), and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11) reactivity. Treatment procedures in 51 patients consisted of simple tumorectomy (16) and wide excision (33). Five and 31 patients received neoadjuvant and adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48 patients, range 7-276 months; median 38 months) showed a 45% local recurrence rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at diagnosis. Five-year overall, metastasis-free, and local recurrence-free survivals were 57%, 50%, and 48%, respectively. Patient age > or =60 years, truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and incomplete tumor excision were significant adverse prognostic factors. Tumor grade and histology did not affect patient outcome. In conclusion, pleomorphic liposarcoma is a rare, often deep-seated and limb-based aggressive and metastasizing neoplasm of late adulthood. It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome.

Small intestine without mucosa as a growing vascular conduit: a porcine experimental study.

OBJECTIVE: This study was conducted to check the feasibility of using small intestine without mucosa as a growing vascular conduit. METHOD: Autologous proximal jejunum without mucosa after treatment with heparin bonding was used as a free inferior vena cava interpositional graft between the renal veins and bifurcation of inferior vena cava in 8 piglets. Intravenous ultrasonography was performed at 1 to 3 months after the operation and at autopsy. RESULTS: One intraoperative death was related to anesthesia. At a mean follow-up of 80 days for the 7 surviving pigs, the weight had increased by 201%, from a mean of 32 kg to a mean of 94 kg. The grafts had increased in length by 128%, from a mean of 2.3 cm at implantation to a mean of 5.1 cm (P <.018) at explantation. In 6 animals the diameter of the graft was equal to that of the adjacent inferior vena cava. At postmortem examination, 6 grafts were patent. The single blocked graft had been patent 1 month after surgery. One graft had extensive septae inside, 2 had minor septae, 2 had microscopic septae, and 2 had no septae at all. Normal appearing adventitia, fibrous tissue, and endothelium (factor VIII-related antigen positive) lined all the grafts. In all 7 grafts, scattered proliferating fibroblasts (MIB1 positive) were observed. CONCLUSIONS: Small intestine without mucosa remodels and acts like a live, growing, layered, endothelialized, nonthrombogenic (after re-endothelialization) vascular conduit in a growing pig. This graft material could have potential as a growing vascular conduit in children.

Application of molecular genetics to the diagnosis of lymphoid-rich effusions: study of 95 cases with concomitant immunophenotyping.

The cytological differentiation between reactive lymphocytosis and malignant lymphoma in serous effusions is often difficult. The present study was designed to evaluate the potential contribution of molecular genetic clonality analysis to a solution to this problem. We examined the cytological specimens of 95 consecutive patients collected during a 4-yr period, including 74 pleural, 20 peritoneal, and one pericardial fluids. Cytological diagnosis in the 95 lymphocyte-rich effusions was positive for lymphoma in 20 cases, suspicious for lymphoma in 26 cases, and negative in 49 cases. The analysis by ICC was not carried out, inconclusive, or noninterpretable in 25 cases. In five cases molecular genetic analysis was hampered by technical problems. By immunocytochemistry, eight additional cases of lymphoma were detected and lineage classification was achieved in 15 of the 20 cytologically positive effusions. PCR and Southern blot analysis were used to assess B- and T-cell clonality. Monoclonality was found in 40 (42%) of the 95 effusions analyzed. One-third of the effusions with a monoclonal B-cell gene rearrangement were detected by Southern blot analysis but not by the PCR performed in parallel. The results of molecular genetic analysis were corroborated by histological findings and/or clinical evolution in 15 cases. Our results indicate that molecular genetic analysis is a useful tool in the analysis of lymphocyte-rich serous effusions.

[Extra neural perineurioma: an unusal renal tumor]. / Périneurome extra-neural: une tumeur rénale inhabituelle.

Neoplasia composed of perineurial cells include intraneural and extraneural perineurioma. The latter is a rare tumor often observed in cutaneous tissue. We report a case of extraneural perineurioma developed at the upper pole of the left kidney and found during the assessment of a repetitive urinary tract infection in a 26 years old man. The tumor was composed of spindle-shaped cells arranged in a storiform pattern. The immunohistochemical pattern was EMA+, PS100-.

Role of metallothioneins in irradiated human rectal carcinoma.

BACKGROUND: Metallothioneins (MT) are low-molecular weight, metal-binding proteins that play a role in cellular proliferation and differentiation, as well as in cellular defense mechanisms. They act as scavengers of free radicals produced by irradiation. A number of in vitro and in vivo studies have linked overexpression of cellular MT with tumor cell resistance to radiation. This is the first study that investigates whether MT expression is involved in the radioresistance of rectal carcinoma. METHODS: Using a mouse monoclonal antibody, MT expression was analyzed by immunohistochemistry on surgical samples (n = 85) from 85 patients with locally advanced rectal carcinoma who were treated preoperatively with a hyperfractionated and accelerated radiotherapy schedule and on tumor biopsies (n = 13) obtained before treatment. The potential correlations between MT expression and pathologic variables and survival were examined. RESULTS: MT were expressed strongly in both the cytoplasm and nucleus of tumor cells in 7 biopsy and 42 surgical samples. A comparison of MT expression in biopsy and surgical specimens showed that MT expression did not change after irradiation in most cases. Against all expectations, MT were expressed more frequently in tumors from responders than in those from the nonresponders (P = 0.02). There was no correlation between MT expression and tumor stage, histology after radiotherapy, or survival. CONCLUSION: These findings do not Cansupport the hypothesis that MT overexpression at the end of radiotherapy is a marker for radiation resistance.

Expression of NDRG1, a differentiation-related gene, in human tissues.

NDRG1 is a member of the new N-myc downregulated gene (NDRG) family which belongs to the alpha/beta hydrolase superfamily, but without presenting a hydrolytic catalytic site. Diverse physiological and pathological conditions (hypoxia, cellular differentiation, heavy metal, N-myc, neoplasia) modulate NDRG1 transcription, mRNA stability, and translation. In this report we present the immunohistochemical localization of NDRG1 in a large set of normal human tissues at light and electron microscopic levels. The immunoreactivity of NDRG1 is mostly found in epithelial cells with different aspects. We observed NDRG1 primarily in the cytoplasm, but it is also associated with the cellular membrane and adherens junctions. Given the strong upregulation of NDRG1 under hypoxia and its nuclear localization, we propose a role for NDRG1 in protection from ischemic cell damage. The multiple localizations of this protein also suggest pleiotropic functions amongst which a functional involvement in the E-cadherin/catenin complex.