Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study.

INTRODUCTION: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. METHODS: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. RESULTS: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P<0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous (P=0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade (P=0.977) and location (P=0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion (P=0.387). CONCLUSION: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.

Accuracy of genomic evaluation with weighted single-step genomic best linear unbiased prediction for milk production traits, udder type traits, and somatic cell scores in French dairy goats.

Genomic evaluation of French dairy goats is routinely conducted using the single-step genomic BLUP (ssGBLUP) method. This method has the advantage of simultaneously using all phenotypes, pedigrees, and genotypes. However, ssGBLUP assumes that all SNP explain the same amount of genetic variance, which is unlikely in the case of traits whose major genes or QTL are segregating. In this study, we investigated the effect of weighted ssGBLUP and its alternatives, which give more weight to SNP associated with the trait, on the accuracy of genomic evaluation of milk production, udder type traits, and somatic cell scores. The data set included 2,955 genotyped animals and 2,543,680 pedigree animals. The number of phenotypes varied with the trait. The accuracy of genomic evaluation was assessed on 205 genotyped Alpine and 146 genotyped Saanen goats born between 2009 and 2012. For traits with unknown QTL, weighted ssGBLUP was less accurate than, or as accurate as, ssGBLUP. For traits with identified QTL (i.e., QTL only present in the Saanen breed), weighted ssGBLUP outperformed ssGBLUP by between 2 and 14%.

Use of meta-analyses and joint analyses to select variants in whole genome sequences for genomic evaluation: An application in milk production of French dairy cattle breeds.

As a result of the 1000 Bull Genome Project, it has become possible to impute millions of variants, with many of these potentially causative for traits of interest, for thousands of animals that have been genotyped with medium-density chips. This enormous source of data opens up very interesting possibilities for the inclusion of these variants in genomic evaluations. However, for computational reasons, it is not possible to include all variants in genomic evaluation procedures. One potential approach could be to select the most relevant variants based on the results of genome-wide association studies (GWAS); however, the identification of causative mutations is still difficult with this method, partly because of weak imputation accuracy for rare variants. To address this problem, this study assesses the ability of different approaches based on multi-breed GWAS (joint and meta-analyses) to identify single-nucleotide polymorphisms (SNP) for use in genomic evaluation in the 3 main French dairy cattle breeds. A total of 6,262 Holstein bulls, 2,434 Montbéliarde bulls, and 2,175 Normande bulls with daughter yield deviations for 5 milk production traits were imputed for 27 million variants. Within-breed and joint (including all 3 breeds) GWAS were performed and 3 models of meta-analysis were tested: fixed effect, random effect, and Z-score. Comparison of the results of within- and multi-breed GWAS showed that most of the quantitative trait loci identified using within-breed approaches were also found with multi-breed methods. However, the most significant variants identified in each region differed depending on the method used. To determine which approach highlighted the most predictive SNP for each trait, we used a marker-assisted best unbiased linear prediction model to evaluate lists of SNP generated by the different GWAS methods; each list contained between 25 and 2,000 candidate variants per trait, which were identified using a single within- or multi-breed GWAS approach. Among all the multi-breed methods tested in this study, variant selection based on meta-analysis (fixed effect) resulted in the most-accurate genomic evaluation (+1 to +3 points compared with other multi-breed approaches). However, the accuracies of genomic evaluation were always better when variants were selected using the results of within-breed GWAS. As has generally been found in studies of quantitative trait loci, these results suggest that part of the genetic variance of milk production traits is breed specific in Holstein, Montbéliarde, and Normande cattle.

The role of the OIE in information exchange and the control of animal diseases, including zoonoses.

The growing importance of animal diseases and zoonoses at a time when globalisation has increased movements of people, animals and animal products across the globe, has strengthened the role of the World Organisation for Animal Health (OIE) in animal disease control. The OIE's mandate since its establishment in 1924 has been to facilitate the exchange of public health, animal health and scientific information, and to further the control and eradication of animal diseases. The OIE is recognised by the World Trade Organization Agreement on the Application of Sanitary and Phytosanitary Measures as the international reference organisation for animal diseases and zoonoses, especially for standard setting. The standards adopted by the World Assembly of OIE Delegates on veterinary public health and animal health feature in the OlE Terrestrial Animal Health Code, the Aquatic Animal Health Code, the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals and the Manual of Diagnostic Tests for Aquatic Animals. The OlE is also a reference organisation for the exchange of public and animal health information among Member Countries, through an information, reporting and warning system based on transparent communication between countries. The OIE provides scientific expertise in ascertaining countries' status with regard to notifiable diseases, enabling them to secure official recognition as being free from foot and mouth disease, African horse sickness, contagious bovine pleuropneumonia and bovine spongiform encephalopathy. The OIE also contributes its scientific expertise to stakeholder training on the surveillance and control of animal diseases and zoonoses and to the evaluation of the performance of Veterinary Services, to enhance theirwork asthe cornerstone of their countries' disease control efforts.

Economic analysis and costing of animal health: a literature review of methods and importance.

Myriads of data, a host of methods, but no single universal indicator. The Performance of Veterinary Services (PVS) Gap Analysis helps to quantify the needs of national Veterinary Services. In a world of scarce public financial resources and heightened transparency and accountability, official Veterinary Services (national Veterinary Authorities) must be able to justify their needs in economic and budgetary terms to their line minister, national parliament and the public at large, or in negotiations with donors. Animal health and Veterinary Service activities are a global public good. It is the responsibility of governments to maintain animal health systems, including networks for the surveillance and control of animal diseases to ensure the early detection of suspected animal disease outbreaks, a rapid response and, where possible, eradication of animal disease outbreaks 'at source'. The establishment of animal health systems is a core responsibility of the State, and it requires the use of public funds, although it does not preclude public-private partnerships and strategies for ensuring complementarity between the partners concerned. The PVS Gap Analysis mission of the World Organisation for Animal Health (OIE) is a method for analysing and quantifying disparities between a baseline situation (determined by PVS Evaluation using the OIE PVS Tool) and the target levels set by the country itself in accordance with its priorities. An added advantage is that the method can be used for training and awareness raising.

[Role for aromatase inhibitors as adjuvant treatment of breast cancer in menopaused women: facts and questions in 2005]. / Place des inhibiteurs de l'aromatase dans le cancer du sein de la femme ménopausée, en situation adjuvante: les acquis et les incertitudes en 2005.

After a dominant role for more than 30 years, tamoxifen has been progressively replaced by aromatase inhibitors as adjuvant treatment for breast cancer in the menopaused woman. We present here a recall of the mechanisms of action involved together with a review of clinical trials leading to the current situation. Giving trial results in detail, we discuss the current evidence as well as open questions. The populations concerned and trial methodologies are analyzed. Comparative tolerance is detailed. Several questions remain open, either due to the lack of evidence to be obtained from ongoing trials or sufficient follow-up. The evidence presented is commented in light of the American (ASCO) and European (Saint-Gallen) or French (Saint-Paul) guidelines.

[Rhabdomyolysis induced by fenofibrate monotherapy]. / Rhabdomyolyse induite par le fénofibrate en monothérapie.

INTRODUCTION: Rhabdomyolysis with fibrate have been reported when fibrate are associated with statin or during renal insufficiency or hypothyroidism. CASE RECORD: We describe one patient with diabetes mellitus treated by fenofibrate monotherapy since several years; 48 h after gliclazide therapy was introduced, rhabdomyolysis occurred. DISCUSSION: Responsibilities of deshydratation and / or drug interaction with gliclazide. are discussed.

[Thyroid-associated ophthalmopathy: physiopathology, endocrine status]. / Orbitopathie dysthyroïdiennne: physiopathologie, équilibre hormonal.

The pathogenesis of Graves' ophthalmopathy remains uncertain. An inflammatory reaction is well established in orbital tissues in Graves' thyrotoxicosis. This inflammation is associated with antithyroid antibody action, but is not systematic in autoimmune hyperthyroidism patients. If ocular manifestations are pathognomonic for Graves' disease they can present in association with euthyroidism or hypothyroidism. Ophthalmopathy factors could be genetically determined but environmental parameters such as smoking and stress may also be involved, supporting the hypothesis that the autoimmune process in this ocular inflammation could be modulated in each patient based on personal and environmental factors.

[The major trends of the French accreditation process. A review of the first 182 reports published]. / Les grandes tendances de l'accréditation. Bilan des 182 premiers comptes-rendus publiés.

OBJECTIVES: To reply to the following questions: what is the status of the accreditation process and what are the general trends pointed out by the experts-visitors ? METHODS: A study was conducted on the 182 accreditation reports regarding health centres, published by the Anaes from June 2000 to July 2002. A reading scale was developed and data was registered in the database. Statistical analysis first described the hospitals (legal status, location, size, number of sites, presence or lack of technical devices, emergency units, and consultations) and then matched them with the specific parameters of the accreditation process (date of involvement, date of audit, date of the accreditation deliberation, number of experts and visitors and number and type of decisions. RESULTS: The results underlined the most frequent decisions among the 10 referentials of the accreditation process. The patients' case reports and the management of quality and prevention predominated. Recent French laws and the decision of the Anaes to apply these themes in their strategic orientation can explain this. COMMENTS: The large hospital size and multi-sites organisation appeared to be negative elements and justify the apprehension felt by the 'major hospitals'.

[Hashimoto encephalopathy. Analysis of four case reports]. / Encéphalopathie de Hashimoto. Analyse de quatre observations.

INTRODUCTION: Encephalopathy associated with Hashimoto's thyroiditis has been recognized for more than 30 years and is probably underestimated. EXEGESIS: We report four patients with Hashimoto's thyroiditis who presented neurological or psychiatric features. There were three women and one man, with a mean age of 68 years. Neurological presentations were various: seizures, psychotic episodes, altered consciousness, hallucinations without usual aetiological diseases (infectious, metabolic, neoplasic, vascular, etc.). Neurological investigations (EEG, brain CT, magnetic resonance imaging) were unspecific. In all cases, a moderately high CSF protein level without pleocytosis was found. Patients presented slight hypothyroidism with high titers of antithyroperoxidase antibodies. Despite hormone therapy replacement, neurological features persisted. Outcome was favorable under steroid therapy. CONCLUSION: Hashimoto's encephalopathy must be considered in the face of neuropsychiatric manifestations without obvious etiology. Pathogenic mechanisms are not clear but probably involve autoimmune cerebral vasculitis because of the efficacy of steroids.

Ovarian tissue cryopreservation and gynecologic oncology: a review.

Sperm cryopreservation permits young men, undergoing cancer treatments, to preserve their fertility. Ovarian tissue cryopreservation have the same goal for young women and could also be an option for children. However, only primordial follicles survive after freezing and a follicular maturation is needed after thawing. This maturation has not yet been realized in humans, pregnancies have only been obtained in animal models. As cryopreservation is yet effective in humans, many teams have already cryopreserved the ovarian tissue of patients who have nothing to lose as their follicular reserve would have been destroyed or severely depleted by cancer treatment. The preservation of fertility is rarely an issue in gynecologic oncology because it usually concerns post-menopausal women. However, they are early-onset forms of gynecologic cancers and in these cases fertility is often threatened. Ovarian tissue cryopreservation may be performed when curative or prophylactic ovariectomy must be undergone, when chemotherapy with high-dose alkylating agents is planned or when pelvic radiation is needed (particularly in cases requiring chemotherapy combined with radiotherapy). In some of these situations it would be dangerous to graft back the tissue to the patient as cancer cells could remain within the grafts, the best solution in this case would be the in vitro follicular maturation.

Comparison of follicle steroidogenesis from normal and polycystic ovaries in women undergoing IVF: relationship between steroid concentrations, follicle size, oocyte quality and fecundability.

Studies of ovarian stimulation for IVF have suggested a relationship between follicle size and pregnancy rates. Furthermore the follicular endocrine environment is correlated with oocyte quality. The aim of this study was first to verify the relationship between follicular steroid content, follicular size, oocyte maturity and fertilization outcome in women with normal ovaries following recombinant human FSH (rhFSH). Secondly this study was extended to women with polycystic ovarian syndrome (PCOS). Fifty-nine patients (31 normal, 28 PCOS) underwent conventional IVF with rhFSH induction. Follicular diameter was classified as small (8-13 mm) or large (>14 mm) and sex steroid content was analysed for each group. Oocyte maturity was studied according to nuclear maturation the day after fertilization. In both ovulation groups, 17 beta-oestradiol and progesterone concentration were significantly higher in large follicles with meiotically competent oocytes compared with those containing meiotically incompetent oocytes. Testosterone levels were increased in PCOS follicles compared with normal patients, with no difference between corresponding sub-groups of follicles with meiotically competent oocytes. The relationship between follicle size and embryo development showed that 14 mm could be a threshold value following rhFSH induction in normal or PCOS women.

[Hyperhomocysteinemia and pregnancy: a dangerous association]. / Hyperhomocystéinémie et grossesse : une association dangereuse.

Homocysteine results from the demethylation of the essential amino acid methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors (vit. B6, B9 and B12). Genetic abnormality in these enzymes or deficiency of these vitamins lead to Hyperhomocysteinemia. Hyperhomocysteinemia belongs among the congenital thrombophilies and is a long-known vascular disease risk factor. The discovery that hyperhomocysteinemia may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients.

[Indications for cryopreservation of ovarian tissue]. / Indications de la cryopréservation du tissu ovarien.

BACKGROUND: The first attempts at ovarian tissue cryopreservation (OTCP) were performed in the 1950s. Recent research efforts have demonstrated the possibility of obtaining pregnancy with this technique in three animal species and have shown good primordial human follicle survival up through the freezing process. POTENTIAL INDICATIONS: OTCP is a procedure designed to protect ovarian tissue from threats to its follicular reserves. The first threat is the time-related massive physiological destruction of the follicular reserve ending with menopause. OTCP would enable this wastage to be arrested, thereby prolonging ovarian cycling beyond limits. Conditions producing premature menopause, when known in advance, may also potentially benefit from OTCP. The iatrogenic destruction of the follicular reserve by radiation therapy or alkylating agents is another situation where OTCP would enable the patient's fertility to be preserved. Among these clinical settings, iatrogenic destruction of follicular stocks appears to us, with the current state of research, to be an acceptable indication for OTCP.

Use of a standardized reconstructed epidermis kit to assess in vitro the tolerance and the efficacy of cosmetics.

The development and validation of alternative methods to animal testing is one of the major priorities for the cosmetic industry. These methods must be reproducible and predictive of the effect of cosmetics during normal use by the consumer. Among alternative methods recently proposed, those using reconstructed human epidermis kits are the most promising approach for this purpose, as these models mimic the site of product application, allow topical application and the assessment of some clinical reactions. However, the realistic use of these models requires reproducibility and relevance of the results. The achievement of these conditions could allow the evaluation of large amounts of products, their comparisons and the generation of data banks on finished products and their ingredients. Only kits manufactured on an industrial scale and in stringent conditions of quality assurance can meet these requirements. As an example, both the criteria for industrial scale usage and the results of reproducibility of results obtained over a 4-year period (135 batches) are reported here, in terms of histological and biochemical criteria (generally used to assess the efficacy or tolerance), for a reconstructed human epidermis elaborated as a kit, EPISKIN(R). These results may provide the framework for a validation and recognition of the model, within guidelines for the assessment of the efficacy and tolerance of cosmetics.

Recombinant human follicle stimulating hormone versus human menopausal gonadotrophin induction: effects in mature follicle endocrinology.

To investigate follicular effects of recombinant human follicle stimulating hormone (rhFSH) induction on women with polycystic ovary syndrome (PCOS), steroid content was compared in mature follicles obtained using a long luteinizing hormone-releasing hormone agonist plus rhFSH or human menopausal gonadotrophin (HMG) in PCOS women and controls participating in an in-vitro fertilization programme. Follicular fluids (144 samples) were collected at oocyte retrieval by individual selective aspiration. Oocyte maturity and fecundability were assessed. Plasma and intrafollicular 17beta-oestradiol, progesterone, testosterone concentrations were assayed individually. No significant difference was seen in oocyte maturity and fecundability between PCOS and controls following rhFSH, or between PCOS rhFSH and HMG group. 17beta-oestradiol, testosterone and progesterone concentrations were lower in PCOS follicular fluid following rhFSH than HMG but the difference was not significant. Progesterone concentration, 17beta-oestradiol/progesterone, 17beta-oestradiol/testosterone were significantly different between the two induction groups, for PCOS fertilized oocyte follicles (P = 0.01, P < 0.05 and P < 0.05 respectively). Steroidogenic enzymatic activity seems to be regulated in healthy follicular cells in PCOS as well as in normal patients upon ovarian induction. Following rhFSH, higher PCOS follicular progesterone concentrations leading to a theoretically increased fecundability could suggest that recombinant FSH is a better inducer which needs to be confirmed.

[Assessment of sub-clinical thyroid disfunction in aged hospitalized patients in Limousin]. / Evaluation des dysthyroïdies infra-cliniques chez des patients âgés hospitalisés en Limousin.

UNLABELLED: The aims of the study were to assess the prevalence of sub-clinical thyroid dysfunction in older patients and to analyze morphological and immunological thyroid abnormalities. SUBJECTS AND METHODS: The effect of aging on thyroid function morphology and immunology was studied in 102 french patients (70 women and 32 men) with a mean age of 81.7 +/- 7.3 years (65-101 years). All patients were hospitalized with different pathological conditions but without any thyroid disease. Patients with treatment or iodine substance which could modify thyroid function were excluded. Serum Free thyroxine (FT4) and TSH levels were detected by RIA. Morphological thyroid study was performed by clinical evaluation and ultrasonography. Two sub-groups of patients were distinguished according to immunological detection tests: In group A (n = 64) immunological parameter was performed by antithyroid microsomal antibodies and in group B (N = 38) by thyroid peroxidase antibodies. RESULTS: We found 4 hypothyroidisms (3.9%), 3 hyperthyroidisms (3%) and 4 marginal isolated high FT4 levels. Elevated levels of FT4 was observed in 3 patients and 1 care of low T4 was described. All patients with abnormal hormonal levels were female. Other patient had normal thyroid function: mean level FT4 was 11.2 +/- 2.2 pg/ml (N: 7-17) and mean level TSH was 1.6 +/- 0.8 mU/l (N: 0.2-4). These values are comparable to those observed in adult populations. Incidence of thyroid autoimmunity was very low (3.9%) in this series compared with previous data. From the morphological analysis, we found 32 morphological abnormalities (31.4%), without strong relation with thyroid dysfunction. Nodule prevalence was near 15% and goiter near 10%.

Selective killing of osteosarcoma cells in culture after retroviral mediated gene transfer of a herpes simplex thymidine kinase suicide gene.

As conventional therapy of osteosarcoma is aggressive and its success relatively poor, notably in cases relapse, we investigated the therapeutic effect of retroviral herpes simplex thymidine kinase (HSV1-TK) gene transfer into a human osteosarcoma cell line. Transfected target cells are sensitive to ganciclovir (GCV) (IC50 0.1 microM), and a potent bystander effect, by which cell death can be induced in HSV1-TK negative dividing cells located in the vicinity of HSV1-TK positive ones, is demonstrated. This is significant for clinical applications as no available gene transfer method can achieve 100% transduction to target cells.