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.

[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.

[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.

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.

[Early menopause]. / Les ménopauses précoces.

Early menopause due to an exhaustion of the ovarian follicles before the age of 40 years occurs in approximately 1% of women in this age range. Clinical signs of estrogen deficiency with amenorrhea and sterility are usually confirmed by hypergonadotrope hypogonadism at laboratory tests. The syndrome is to be differentiated from gonadotrophine resistant ovaries and rare gonadotrope adenomas. Ovary biopsy shows more or less complete destruction of the follicles. There are many causes of early menopause including abnormal number or structure of chromosome X in 15-20% of the cases. Certain metabolic disorders and viral infections can also be incriminated. Finally surgery, radiotherapy or chemotherapy can be the cause of iatrogenic menopause. To determine prognosis, the woman's follicular capacity must be estimated. Estrogen therapy is currently the best choice to preserve chances for ovulation and pregnancy. When there is no remaining follicular capacity, ovum donation may be a solution. Finally, all patients should be given hormone substitution therapy due to the long-term risk of estrogen-progesterone deficiency.

[Limits of laparoscopic surgery of adrenal glands. Apropos of 17 cases and a review of the literature]. / Limites de la résection coelio-chirurgicale des surrénales. Dix-sept observations et revue de la littérature.

OBJECTIVES: To review own cases of laparoscopic adrenalectomy in order to better ascertain limits therapeutic management and indications, compared with the literature data. PATIENTS-METHODS: Medical files of 15 patients after 17 laparoscopic adrenalectomies in the Dupuytren hospital of Limoges from February 1994 to November 1996, were analyzed 10 women and 5 men mean aged 59.4 years (22-77) were operated. Transperitoneal laparoscopic adrenal resection indications were: Conn adenoma (3), Cushing discase (2 bilateral resection), adrenal incidentaloma (9) and adrenal metastasis (1). RESULTS: Mean (range) of adrenal tumor size was 4 cm (0.8-7.5 cm). Operating times mean (range) was: 3 hours 40 minutes (1 h 50-6 h). Mean (range) of hospital stay was 3.4 day (3-6), marquedly reduced than open traditional adrenal surgery. Neither complication nor mortality per- or post-operative were present. But the laparoscopic operation required conversion to an open adrenal resection in 3 cases (18%). COMMENTS: Laparoscopic adrenalectomy offer real advantages: effectiveness and safety with a reduced time hospital discharge. Indications and adrenal size limits need to be precised on largest studies.

[Inhibition of steroidogenesis by ketoconazole. Therapeutic uses]. / Inhibition de la stéroïdogenèse par le kétoconazole. Applications thérapeutiques.

Ketoconazole, a broad-spectrum imidazole antimycotic agent, interferes with cytochrome P-450 enzyme systems in several organs (testis, ovary, adrenal gland, kidney, liver). It inhibits cholesterol synthesis by a dose-dependent transient braking of the 14 alpha-demethylase. Steroidogenesis is inhibited by its action on the C17-20 lyase, the cholesterol side-chain cleavage enzyme and the 17 alpha-hydroxylase. In gonads it inhibits aromatase and adrenocortical steroid biosynthesis is also inhibited at the 11 beta-hydroxylation and 18-hydroxylation steps. Its antiandrogenic effect may be useful in the management of metastatic prostate carcinoma and in testotoxicosis, its usefulness in the treatment of hirsutism is more questionable. Its anticortisolic effect may be useful in most Cushing's syndromes, where drug control of hypercortisolism is suitable for patients undergoing surgery, as well as those in whom more definitive treatment is delayed. Its usefulness as inhibitor of vitamin D or mineralocorticoids requires further investigation.

[Orthotopic autografts of ovarian slices in pregnant rats]. / Autogreffes orthotopiques de fragments ovariens chez le rat avec grossesses.

We carried out orthotopic autografts of ovarian tissue on 15 Wistar rats. One ovary has been removed and cut in 2 or 3 slices. The other ovary has been removed, and the controlateral slices grafted in the empty ovarian bursa by mean of a microscope, without vascular anastomosis. The endocrine function of the graft was assessed by checking the vaginal smears. The animals were mated. Two of them became pregnant with normal offsprings, two others has vaginal bleeding which could be miscarriages. This experimentation suggests that the orthotopic autograft of ovarian slices is possible in rats. The endocrine function of the ovary is restored with a very good rate. Fertility is restored for a small proportion of animals.