Minimally-invasive surgery for liver metastases.

The practice of laparoscopic liver surgery has developed gradually, and most liver resections seem currently feasible and safe for selected patients in centers where surgeons are experienced both in liver surgery and in laparoscopic surgery. However, further studies would be required, especially for long-term oncological results and for major hepatectomy follow-up, before laparoscopic hepatectomy becomes a common alternative to open liver surgeries. Laparoscopic major hepatectomy is a recent technique, due to its significant complexity. In this review, we showed that patients undergoing laparoscopic hepatectomy for liver metastases experienced decreased rates of overall and major postoperative complications without any compromise on long-term outcomes compared to patients treated by open resection.

A method for guideline development: assessing practical feasibility and adaptation of thyroid nodule guidelines.

The objective of this study was to assess adaptation and feasibility of practice guidelines for thyroid nodule management. For one month physicians completed a self-administered semi-structured questionnaire concerning a draft version of the guidelines for each consecutive patient. A sample group of 20 endocrinologists, 20 surgeons and 120 general practitioners from all parts of France took part in this study. The main outcome measures were whether the case description was found by the physicians, and whether recommendations were found and agreement with these recommendations were assessed. We found that two hundred and fifty-three patients (of whom 85% were women) were included in the study: 52% were seen for a surgical decision; 20% for diagnosis or screening and 28% for follow-up. Four percent of the women were pregnant; 2% of the patients had a large nodule; and 2%, a retrosternal nodule. These last three situations had not been well identified in the draft guidelines. The patient's case description was appropriately identified in 75% of the responses. Most cases reported as being not found were, however, covered by the guidelines. Physicians in private practice were less likely than the others to identify their patient's cases. Physicians agreed with the recommendation in 77% of cases. General practitioners were more likely and endocrinologists less likely than surgeons to disagree. Most disagreements and alternative proposals were not evidence-based. Our conclusion is that this study shows that the draft guidelines were applicable, and allowed minor improvements of the final version. Adapting guidelines to practice could improve their use and, consequently, the quality of health care.

[Treatment of hypothyroidism]. / Traitement de l'hypothyroïdie.

Levothyroxine sodium (LT4) is the treatment of choice for the management of hypothyroidism. The aim of the treatment is to obtain a permanent clinical and biological (normal TSH values) euthyroid state. Before initiating therapy, hypothyroidism has to be confirmed and, in adults, the risk of coronary heart disease to be evaluated. Adults require approximately 1.6-1.7 micrograms/kg/day for full replacement. Replacement doses may vary with various factors (age, weight, pregnancy, cause of the thyroid disease, degree of failure). Therapy is initiated gradually, usually starting with 50-100 micrograms LT4 in the adults without coronary heart disease risk. For older patients or patients at risk for cardiac disease, a lower initial dosage (12.5-25 micrograms LT4) and lower increments are indicated. Once the appropriate dose has been established, periodic monitoring, first at six months and then annually or every 6 months, is essential. Patients should not be evaluated before 6 weeks with the same dosage. Patient information is also important to improve compliance. Therapy for subclinical hypothyroidism is controversial. It is probably advisable if thyroid autoantibodies are positive and particularly if non specific signs or symptoms are present. Other forms (central hypothyroidism, iatrogenic transient and congenital forms, supra substitutive therapy for thyroid cancers) require a specific and specialised approach.

Including practice data to improve evidence-based guidelines. Example of guidelines on the management of thyroid nodules.

Although clinical guidelines are based on the best evidence available, their proliferation has often failed to change actual practice. One of the many explanations suggested is that there is a gap between the expectations of the targeted professionals and the recommendations in the guidelines. In this study, we attempted to take into account the state of current practice and the physicians' priorities. Using the example of guidelines on the management of thyroid nodules, three different surveys have been conducted: (1) an analysis of physicians' expectations and practice through a postal questionnaire to define appropriate questions; (2) a survey of the professionals' expert opinions, and (3) a prospective study of the use of these guidelines in the management of 253 patients. The results of these surveys have modified the development of the guidelines, and helped us to adapt the content of the guidelines to match physicians' practices more closely.

Myocardial and vascular adrenergic alterations in a rat model of endotoxin shock: reversal by an anti-tumor necrosis factor-alpha monoclonal antibody.

OBJECTIVES: a) To investigate responsiveness to exogenous catecholamines in rat endotoxin shock by studying both myocardial and vascular functional parameters, and to determine the relationship of these parameters with other relevant biological parameters of the adrenergic pathway, such as myocardial beta-adrenergic receptors and cyclic adenosine monophosphate (cAMP); b) to investigate the role of tumor necrosis factor (TNF)-alpha via prophylactic anti-TNF-alpha monoclonal antibody administration. DESIGN: Experimental, comparative hospital. SETTING: Laboratory in a university hospital. SUBJECTS: Male Sprague-Dawley rats, weighing 280 to 340 g. INTERVENTIONS: Intravenous injection of Escherichia coli endotoxin (5 mg/100 g) in the first group; injection of the same dose of endotoxin preceded by 2 mg/100 g of anti-TNF-alpha monoclonal antibody in the second group; injection of saline in the third (control) group. MEASUREMENTS AND MAIN RESULTS: TNF-alpha concentration was measured before and during the first 3 hrs in all three groups. Myocardial and vascular functional parameters were obtained, respectively, from Langendorff perfused hearts and isolated aortic rings. Adrenergic biochemical parameters (catecholamines, density and affinity of beta-receptors, and isoproterenol-stimulated myocardial cAMP) were determined 3 hrs after injections in the three groups. After endotoxin injection, serum TNF-alpha concentrations peaked at 60 mins (2496 +/- 412 pg/mL) and returned slowly to control values at 3 hrs; serum TNF-alpha concentrations remained under the limit of detection in the other two groups. When compared with the control group, plasma concentrations of epinephrine and norepinephrine were significantly (p < .05) increased. Baseline values for differential left ventricular pressure and coronary flow were significantly (p < .001, p < .01, respectively) reduced in the endotoxin group; heart rate remained unchanged. In the endotoxin and control groups, isoproterenol induced a similar increase in differential left ventricular pressure and in heart rate. Anti-TNF-alpha antibody increased cardiac response by partially preventing the decrease by endotoxin in differential left intraventricular pressure. Maximal specific binding of 125iodocyanopindolol and myocardial cAMP accumulation were significantly (p < .01) reduced in the endotoxin group in comparison with the control group. Anti-TNF-alpha antibody prevented the endotoxin-induced decrease in cAMP synthesis (p < .05) but did not modify the density of receptors. Affinity of receptors was similar in the three groups. In aortic rings, endotoxin administration significantly (p < .01) shifted the dose-response curve to norepinephrine to the right, both in the presence and absence of endothelium. NG-monomethyl-L-arginine significantly increased the contractions to attain the control level: p < .001 in the presence of endothelium; p < .05 in the absence of endothelium. Anti-TNF-alpha antibody did not prevent endotoxin-induced vascular hyporeactivity to norepinephrine in either endothelium-intact or -denuded rings, but partially attenuated the decrease in maximal response. CONCLUSIONS: In ex vivo experiments, 3 hrs after endotoxin injection, vascular responsiveness was sharply decreased. This impaired response was improved in vitro by the inhibition of nitric oxide. The heart response to isoproterenol, nevertheless, was maintained, even though there was an obvious decrease in receptor density and an impaired myocardial accumulation of cAMP. Anti-TNF-alpha antibody partially prevented the alteration of both myocardial pressure response to isoproterenol and biochemical parameters, and was not efficacious in preventing vascular hyporeactivity to vasoconstrictor agents.

[Diagnostic strategy for a solitary thyroid nodule. Example of development of recommendations for a practice guideline]. / La stratégie diagnostique devant un nodule thyroïdien isolé. Exemple d'élaboration de recommandations pour la pratique clinique.

The solitary thyroid nodule is frequently observed and many strategies are proposed for the diagnosis of the etiology and for the choice of treatment. Despite many discussions no clear consensus has been so far reached. The french groups concerned by this problem set up a Clinical Practice Guide line with the methodological help of Agence Nationale pour le Développement de l'Evaluation Médicale. Based upon the critical review of the literature a consensus was obtained concerning the natural history of the nodules and the diagnosis value of the complementary explorations. The clinical approach alone completed by a TSH determination gives the therapeutical choice in about 30% of the patient without any other explorations. In the remaining cases 3 methods (isotope scan, echography, cytopuncture) can be used alone or in a combined sequence. So far no strategy can be privilegiated. It is necessary to set up a systematic comparison between the possible strategies and this will be made by the french thyroid specialists after this first step of delimitation of a clinical practise guide line.

Daily insulin treatment relieves long-term hyperalgesia in streptozocin diabetic rats.

Painful neuropathy is common in human diabetes. In rats, experimental diabetes results in altered pain sensitivity. We examined the effect of chronic insulin treatment on diabetes-induced hyperalgesia in streptozocin diabetic rats. A 20-week period of diabetes resulted in a 62% decrease in paw withdrawal thresholds compared with age-matched normal rats. Daily injections of insulin progressively reversed mechanical hyperalgesia to normal values parallel to the correction of hyperglycaemia. When the treatment was stopped, mechanical hyperalgesia reappeared, but never reached the degree of hyperalgesia observed before insulin treatment, suggesting that indirect mechanisms underlie the effect of normoglycaemia on nociception. The present data suggest that appropriate blood glucose control can help relieve pain in long-term diabetes through indirect mechanisms.

Alterations of myocardial and vascular adrenergic receptor-mediated responses in Escherichia coli-induced septic shock in the rat.

OBJECTIVES: To investigate responsiveness to exogenous catecholamines in rat bacteremic shock by studying both myocardial and vascular functional parameters; to determine in the same study the relationship of these parameters with other relevant biological parameters of the adrenergic pathway, such as myocardial beta-adrenergic receptors and cyclic adenosine monophosphate (cAMP); and to indirectly approach the roles of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide. DESIGN: Experimental, comparative study. SETTING: Laboratory in a university hospital. SUBJECTS: Male Sprague-Dawley rats, weighing 270 to 320 g. INTERVENTIONS: Intravenous injection of live Escherichia coli DH5 alpha (2 x 10(10) organisms/kg) or saline (0.6 mL) and comparison of the two groups. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and heart rate (HR) were recorded, and circulating TNF-alpha concentrations were measured, during the first 3 hrs after E. coli administration. Myocardial and vascular functional parameters were obtained, respectively, from Langendorff-perfused hearts and isolated aortic rings. Adrenergic biochemical parameters (catecholamines, density and affinity of beta-receptors, and isoproterenol-stimulated myocardial cAMP) were determined 3 hrs after E. coli injection. Mean arterial pressure decreased within 5 to 60 mins after bacteria injection and returned to basal levels in the last 2 hrs; HR was unchanged. Serum TNF-alpha concentrations peaked at 120 mins (7333 +/- 672 pg/mL) and were still increased at 3 hrs. Plasma concentrations of epinephrine and norepinephrine were significantly (p < .05) increased. Baseline values for differential left ventricular pressure and coronary flow were significantly (p < .0001, p < .001, respectively) reduced; HR remained unchanged. Isoproterenol induced a similar increase in differential left ventricular pressure and in HR. There was no decrease in the functional myocardial response to adrenergic stimulation. beta-adrenergic receptors were similar in density and in affinity in the two groups. Isoproterenol-stimulated myocardial cAMP was significantly (p < .01) reduced compared with the control group. In aortic rings, bacteria administration significantly (p < .01) shifted the dose-response curve to norepinephrine to the right, both in the presence and absence of endothelium. NG-monomethyl-L-arginine significantly increased the contractions to attain the control level: p < .001 in presence of endothelium; p < .05 in absence of endothelium. CONCLUSIONS: In ex vivo experiments, 3 hrs after E. coli injection, vascular responsiveness was sharply decreased. This impaired response was improved by inhibition of nitric oxide. The heart, nevertheless, was still able to modulate its inotropic and chronotropic response to isoproterenol, even though an impaired beta-adrenergic-receptor stimulation of cAMP was already present.

[Management of the thyroid nodule. Preliminary results of a practice survey of 685 general practitioners and specialists]. / Prise en charge du nodule thyroidien. Résultats préliminaires d'une enquête de pratiques auprès de 685 médecins généralistes et spécialistes.

The authors present the preliminary results of a mailed survey of policies for the management of thyroid nodules (TN). This survey involved 685 general practitioners and specialists and was carried out at the initiative of APNET (National Educational Association for Training in Therapeutics) with the aid of ANDEM (National Agency for the Development of Medical Evaluation). Twelve percent of responders (13.1% among GPs) declare that they do not manage TNs. Those have been excluded from the analysis. The answers taken into account come from general practitioners (n = 179), endocrinologists (n = 233), specialist surgeons (n = 64), ENT practitioners (n = 93) and nuclear medicine practitioners (n = 26). The average number of patients with TN seen in a year varies according to the specialty: 6 a year for GPs, 30 in ENT, 89 for endocrinologists, 105 for surgeons. This survey reveals a number of common position: 1) the therapeutic attitude must be customized according to clinical findings and to complementary tests; 2) prescriptions are homogeneous as regards radionuclide scanning (technetium or iodine), TSH assays, ultrasonography and T4 assays; 3) ultrasonography is used in first intention; 4) ultrasonography has limitations, and is regarded by a majority or responders as unable to provide information about benignancy or malignancy. Conversely, responses are much more variable about a number of points: 1) the use of fine needle aspiration cytology which is mainly used by endocrinologists and nuclear medicine practitioners; 2) the management of nodules discovered on ultrasonography: the attitude is different from that adopted with palpable nodules for endocrinologists, surgeons and nuclear medicine practitioners, and identical for most general and ENT practitioners; 3) the usefulness of a suppressing treatment with thyroid hormones. Both general practitioners (47%) and, even more so, specialists (84%) are aware of these differences in practices. Faced to this situation, 69% of specialists are in favor of establishing consistent practices, but a minority (42%) only think that it is possible. Thus recommendations about practices may be useful only if they are adapted to the type of practice and to the conditions of access to complementary tests, and they should be aimed at rationalizing management rather than making it consistent.

Tricyclic antidepressants, thyroid function, and their relationship with the behavioral responses in rats.

We first studied the effects of tricyclic antidepressants (TCAs) on thyroid function in rats in the learned helplessness paradigm. TCAs (clomipramine 32 mg/kg, desipramine 16, 24 mg/kg, or imipramine 8, 16, 32 mg/kg per day) were injected IP for 5 consecutive days. Blood samples were collected 1 hr after the last administration of the antidepressant for radioimmunoassay determination of triiodothyronine (T3) and thyrotropin. Whereas inducing helplessness did not result in any change in T3 and thyroid-stimulating hormone (TSH) levels, TCA therapy dose dependently decreased the T3 levels without changing TSH levels in helpless animals and in naive control rats. To further the investigation, the effects of TCAs on thyroid function were examined using two models of experimentation, one involving diabetes induction, the other using food deprivation; both are known to induce a resistance to TCAs that is reversible under T3 treatment. In both models, a decreased T3 level existed prior to the TCA administration. Although they had no effect on behavior, TCAs further decreased the T3 levels in diabetic and food-restricted rats. This study confirms that TCAs decrease thyroid function and suggests that the antidepressant effect of TCAs is not related to their T3 decreasing effects.

Involvement of angiotensin-converting enzyme inhibition in reversal of helpless behavior evoked by perindopril in rats.

Several clinical investigations have suggested that captopril, an angiotensin-converting enzyme inhibitor (ACEI) currently used as an anti-hypertensive agent, exhibits antidepressant properties in humans. In the present study we evaluated the action of perindopril, another ACEI, and two of its metabolites, the di-acide form perindoprilat, which possesses ACE inhibitory properties, and BDM-4, an inactive metabolite, in the learned helplessness paradigm. In order to confirm a possible action of these drugs via dipeptidyl carboxypeptidase inhibition, we also investigated two inactive analogues of perindopril and perindoprilat. Perindopril (0.06-8 mg/kg per day) and perindoprilat (0.25-8 mg/kg per day) induced a reversal of escape deficits. BMD-4 and two analogues failed to reverse helpless behavior. These results support the hypothesis that ACE inhibition is a key factor in the behavioral antidepressant-like activity of perindopril and perindoprilat.