[Neuropathic pain treatment]. / Traitement des douleurs neuropathiques.

INTRODUCTION: neuropathic pain is a frequent complication and results from numerous mechanisms, (infectious, post traumatic, metabolic, vascular) or toxic (i.e. medications). It is a complex entity due to its pathophysiology and its clinical features, but remains under diagnosed despite medical awareness. MATERIAL AND METHOD: we reviewed the recent literature on evaluation and treatment of neuropathic pain with a focus on published guidelines. RESULTS: scales and questionnaires are available (DN 4, LANSS, etc.) but are not superior to anamnesis and a close physical examination. Usual treatments mostly based on empirical experiences are antidepressants, anti epileptics, calcium channels inhibitors, opioids, and cannabinoids. CONCLUSION: neuropathic pain is a complex and heterogeneous syndrome. Various medications are available but none is specific. The best choice is a drug with few interactions and side effects. Some preventive therapies are promising. We propose a practical guideline based on data from the literature.

INTRODUCTION: les douleurs neuropathiques sont des complications fréquentes, provoquées par de nombreuses affections médicales (infectieuses, traumatiques, métaboliques, vasculaires), par des agents neurotoxiques, médicamenteux ou autres. Elles constituent une entité complexe de par la physiopathologie et la présentation clinique et restent sous-diagnostiquées. Matériel et méthode : une revue de la littérature récente a été effectuée en recherchant les éléments concernant l'évaluation et le traitement des douleurs neuropathiques, ainsi que les directives et guidelines proposées. Résultats : des échelles d'évaluation sont disponibles (DN 4, LANSS, etc.) mais ne remplacent pas l'examen physique et l'anamnèse. Les traitements comprennent des antidépresseurs, des antiépileptiques, des inhibiteurs calciques, des morphiniques, des dérivés cannabinoïdes, et dont l'usage reste majoritairement empirique et non spécifique. Les moyens de prévention restent limités, mais certains d'entre eux sont prometteurs. CONCLUSION: les douleurs neuropathiques constituent une entité complexe et hétérogène qui demande une approche spécifique. Les traitements disponibles concernent une grande variété de médicaments dont aucun n'est spécifique. La préférence ira vers des molécules ayant le moins d'effets secondaires. Une procédure d'évaluation et de traitement est proposée en référence aux données récentes de la littérature.

[Euthanasia and the abuse of conscience clause concept]. / L'euthanasie et le détournement de la clause de conscience.

Since 2002, the Belgian legal framework authorizes the practice of euthanasia, under cer tain clear conditions. All cases have to be reported to the Assessment and Control Commission (ACC). To date, more than 10.000 cases have been reported since 2002. The concept of individual conscience clause is of concern and its use in an institutional dimension is analysed. The role of moral integrity and conscience clause in health care should be downplayed in the field of medicine's core values.

La loi belge qui dépénalise l'euthanasie sous conditions a quatorze ans. Depuis sa mise en application en septembre 2002, plus de 10.000 cas ont été rapportés à la commission fédérale de contrôle et d'évaluation (CFCEE). Le concept de clause de conscience est abordé dans sa dimension individuelle mais également dans le cadre d'un usage institutionnel potentiel. Indépendamment de l'importance que revêtent la clause de conscience et l'intégrité morale, leur usage dans le cadre des soins de santé s'avère parfois abusif et devrait davantage être encadré.

[Euthanasia: status report in 2014]. / Euthanasie: Etat de la situation en 2014.

Since 2002, the Belgian legal framework authorizes the practice of euthanasia, under certain conditions. All cases have to be reported to the Assessment and Control Commission (ACC). To date, more than 6000 cases have been reported since 2002. To make a statement about the Belgian experience requires considering different points: data and evaluation from the ACC reports, their analysis, consequences on medical practice, legal and medical perspectives, critics and attacks about the legal framework, the concept of individual and institutional conscience clause. Regarding all these topics, we note that the Belgian experience is more than an example and shows that adequate answers may be provided to patients experiencing intolerable suffering.

[Continuous sedation: practical and ethical aspects]. / Sédation continue: considérations pratiques et éthiques.

Continuous sedation is an acknowledged medical practice in the management of refractory symptoms at the end of life. Guidelines and recommendations have been proposed in palliative care. This paper presents the state-of-the-art (definitions, indications, technical aspects) on continuous sedation followed by an ethical reflection essentially based on the "double effect" principle, on the impact on life expectancy and the assimilation of continuous sedation as a "natural death". Distinction between continuous sedation and legal euthanasia is clarified.

[A reflection on love, medicine and euthanasia: I know what I like and I like what I know, but is that true?]. / Une réflexion sur l'amour, la médecine et l'euthanasie: je connais ce que j'aime et j'aime ce que je connais, mais est-ce bien vrai?

This paper presents the medical practice according to the occidental philosophy (Platon, Spinoza, Kant). Relationships with the concept of "love" (eros, philia, agape) will be described, and the concept of dignity and autonomy as well. The reflection will focus on the end of life aspects. Although medicine cannot avoid morality, ethic, and deontology, it is also part of philosophy and must warrant the respect of human dignity, especially when a physician helps a patient to die.

[Euthanasia: medications and medical procedures]. / L'euthanasie en pratique, produits et techniques a utiliser.

The Belgian law relative to euthanasia has been published in 2002. A physician is allowed to help a patient with intractable suffering (physical or psychological). Legal conditions are clear. However, nothing is said about medical procedures or medications to be used. The present paper will present specific clinical situations at the end of life, practical procedures and medications. A special focus is made on psychological impact of euthanasia.

[Pregabalin (Lyrica) and neuropathic pain syndromes]. / La prégabaline (Lyrica) et les douleurs neuropathiques périphériques.

Pregabalin is a novel central nervous system (CNS) drug with no interaction at benzodiazepine or GABA receptor. Its mechanism of action is correlated with its high affinity for the alpha/delta submit of the voltage-dependant CNS calcium channel. Pregabalin is rapidly absorbed with at least 90% bioavailable irrespective of dose, does not bind to plasma proteins and is excreted virtually unchanged by the kidneys. Pharmacokinetics are linear and predictable across the therapeutic dose range (150-600 mg/ day). Pregabalin is indicated, like gabapentin, in the treatment of neuropathic pain syndromes like post-herpetic neuralgia (PHN) and diabetic polyneuropathy (DPN). Efficacy in other neuropathic pain syndromes need further investigations. This paper emphasizes advantages and disadvantages on a clinical point of view.

[Euthanasia 2002-2014: The situation in Belgium]. / Euthanasie 2002­2014 : état de la situation en Belgique.

INTRODUCTION: Since 2002, Belgian law has authorized the practice of euthanasia under certain clear conditions. All cases have to be reported to the Assessment and Control Commission (ACC). To date, more than 9000 cases have been reported. AIM: To make a statement about the Belgian experience requires consideration of several different essential points: detailed data and information from the ACC reports, their analysis, consequences on medical practice, problems experienced, legal and medical perspectives, criticism and attacks. The concept of individual and institutional conscience is also considered. Euthanasia for minors has been permitted since March 2014 but, to date, no case has been reported. In the light of what has happened in Belgium, we propose to analyse the legal situation in France. MAIN POINTS AND CONCLUSIONS: The Belgian experience is much more than an example and shows that, in difficult and painful situations, it is possible to meet the expectations of patients experiencing intolerable suffering with great respect and without imposing dogmatically something they do not wish.

Phase I study of docetaxel administered as a 1-hour intravenous infusion on a weekly basis.

PURPOSE: This phase I study of Taxotere (RP 56976, NSC 628503; docetaxel, Rhône-Poulenc Rorer, Antony, France) was undertaken to determine the maximum-tolerated dose (MTD), toxic effects, and basic pharmacokinetics of a day-1 and -8 schedule of this novel semisynthetic product related to Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT). PATIENTS AND METHODS: Thirty-two eligible patients with refractory solid malignancies have been treated with a 1-hour infusion of Taxotere on a day-1 and -8 schedule every 3 weeks as long as patients maintained a polymorphonucleotide count > or = 1,500/microL and a platelet count > or = 100,000/microL. Dose levels tested have ranged between 20 and 110 mg/m2 per course. RESULTS: Considering 128 assessable courses, the main toxicities have been neutropenia (which was dose-limiting), asthenia, alopecia, hypersensitivity reactions, skin toxicity, and edema. No significant cardiac or platelet toxicity has been observed. Seven patients have had aggravation of preexisting paresthesias or new onset of sensory symptoms during Taxotere treatment. The MTD at this schedule appears to be 110 mg/m2 per course, with six of 10 patients at this level experiencing severe toxicity. Five partial remissions have been observed in four heavily pretreated patients with breast cancer and in one patient with adenocarcinoma of unknown origin. Two patients with ovarian cancer have had meaningful decreases in CA125 levels. CONCLUSION: Like Taxol, this novel chemotherapeutic agent appears to possess promising activity in patients with refractory breast and ovarian neoplasms, with tolerable toxicities. Using this schedule, 100 mg/m2 per course is the recommended dose for future phase II trials.

[Two years of legal practice of euthanasia in Belgium: comparison with the Netherlands. First evaluation in a palliative care unit]. / Deux années d'euthanasie dépénalisée en Belgique: comparaison avec les Pays-Bas. Premier bilan d'une unité de soins palliatifs.

The Belgian law relative to euthanasia prescribes that a physician performing an euthanasia has to complete a registration document and to send it within 4 days to the federal commission for control and evaluation of euthanasia. The 259 first documents are described in the report of the commission referred to Parliament on September 17, 2004. The present paper analyses this report and compares its most important data with those published in the Netherlands: apart from the total number of euthanasia's, much smaller in Belgium, and apart from aspects which are specifically related to the Belgian law, the statistical data are very similar in both countries. The difference in the number of registration documents written in French and in Flemish is analyzed and discussed. A first evaluation of the application of the law in a supportive and palliative care unit is reported.

Longitudinal follow-up of TTS-fentanyl use in patients with cancer-related pain: results of a compassionate-use study with special focus on elderly patients.

GOALS OF THE WORK: This open compassionate-use prospective registration study evaluated the tolerability, ease of use and applied doses of transdermal (TTS) fentanyl in adult patients with cancer-related pain requiring strong opioid analgesia. Elderly patients were particularly focussed on. PATIENTS AND METHODS: Previous pain medication was converted to an appropriate dose of TTS-fentanyl. Immediate-release morphine rescue medication was allowed as needed for breakthrough pain. Dose adjustments of TTS-fentanyl, rescue morphine requirements, the ease of use and side-effects were assessed monthly, with special emphasis paid to the severity of constipation and the use of laxatives. MAIN RESULTS: A total of 663 patients with cancer-related pain, including 8% opioid-naive patients, were enrolled; 661 patients used at least 1 patch of TTS-fentanyl. Of these, 455 subjects were assessed at baseline and at 1 post-baseline visit at least. Individual treatment ranged from a few days to 2 1/2 years; TTS-fentanyl doses ranged from 25 to 950 microg/h. The major reason for study termination was non-drug-related death (61%). Approximately 40% of patients reported constipation. The frequency of constipation depended on the rescue morphine dose used, but no dose-relationship was found for TTS-fentanyl. Patient acceptance of the patches was high; around 85% of patients rated convenience as good to excellent The ease of use and tolerability of TTS-fentanyl in the elderly patients were comparable to that in the total population, except for a slight increase of non-serious adverse events. CONCLUSIONS: TTS-fentanyl can be applied as long-term therapy to patients with cancer-related pain, including the elderly.

Diagnosis and treatment of epidural metastases.

Epidural metastases are a common complication of malignancy and are usually considered an oncologic emergency requiring hospitalization and urgent diagnostic and therapeutic interventions. However, patients at high risk for epidural cord compressions can be identified, evaluated, and treated electively before they develop serious neurological deficits. Often this can be accomplished entirely in the outpatient setting. The early diagnosis and treatment of epidural metastases is crucial in preserving ambulation and bowel and bladder function. The possibility of such metastases should be suspected in any cancer patient with back pain.

[Euthanasia: practical implications]. / Euthanasie: implications pratiques sur le terrain.

Techniques used for euthanasia exist and have to be available for doctors. Their use ask for accurate information regarding schedules and pharmacology. Numerous medications may induce death at supratherapeutic doses but few are effective to ensure an end-of life without suffering, in the respect of human dignity. Some specific situation encountered in the terminal phase of life (delirium, dyspnea, bleeding) are described with their medical approaches. Terminal (or controlled) sedation and physician-assisted suicide are discussed. Two effective schedules based on the dutch experience and providing gentle and easy death are presented.

[Opioids in practice]. / Les opiacés en pratique.

The treatment of cancer pain includes various classes of molecules. Among them, morphine and its derivatives are considered as references. The understanding of pharmacological aspects and the control of side effects lead to an adequate pain relief during the illness. The nature of the pain syndrome have basically no influence on the opioid responsiveness. Synthetic opioids are not recommended for cancer pain.

[Transdermal fentanyl]. / Fentanyl (TTS).

Fentanyl is a synthetic pure opioid agonist with a selective activity on mu receptors. Its high liposolubility allows a transdermal administration, using a Transdermal Therapeutic System (TTS). The clinical efficacy is widely demonstrated in the field of cancer pain control. The side effects are those observed with morphine but with less frequent constipation. The adjonction of a short acting morphine in case of acute pain is recommended.

[Pain and cancer]. / Douleurs et cancer.

Pain is one of the most frequent symptoms encountered in oncology which, regarding its complexity and its effects on quality of life, will be better treated with a multidisciplinary approach, for in and out-patients. The knowledge of the pain syndromes associated with an accurate use of pain medicine provide a rapid control of the symptomatology. A coherent use of opioids, the introduction of new drug delivery systems, and the use of new molecules offer new horizons in the control of cancer pain.

[Gabapentin (Neurontin) and cancer pain: a pilot study]. / La gabapentine (Neurontin) et les douleurs cancéreuses: etude pilote.

Gabapentin (GBP) is a new antiepileptic agent with an original spectrum of activity. Its mechanism of action has not yet been fully elucidated but appears not to involve binding to GABA receptors despite being a structural analogue of GABA and is distinct from tricyclic antidepressants (TCAs). It has been shown to modulate high threshold calcium currents in brain neurons. As some other anticonvulsants, GBP has been recently proposed for the treatment of noncancer neuropathic pain like diabetic neuropathy and post herpetic neuralgia (double blind studies with placebo). We prospectively followed 20 cancer patients with advanced disease suffering from neuropathic pain. All were already treated for their pain syndrome. We started with 300 mg of GBP given orally in order to reach a dose of 900 mg on D3. All coanalgesics were stopped before entering the study. The only relevant side effect due to GBP was somnolence, otherwise time limited. GBP treatment was associated with a decrease of opioids doses in 9 patients and a decrease of VAS for pain intensity in all cases. Furthermore, the need of rescue doses decreased in all cases but 2. GBP appears to be one of the most effective drugs for the treatment of neuropathic pain. It is well tolerated and its effectiveness appears shortly after its administration. A synergistic action with opioids is suggested. Despite the small number of patients, our study suggests that GBP could be a treatment of neuropathic pain in cancer. Comparative trials should be performed with other neuropathic pain drugs including TCAs and antiepileptic drugs, especially carbamazepine.

[Terminal medical interventions: psychosocial, medical, ethical and legal aspects]. / Les interventions médicales de dernier recours: aspects psychosociaux, médicaux, éthiques et juridiques.

We give an overview of the available medical solutions to help a patient with refractory symptoms at the end of his life. Patient "competence" must first be evaluated and, even if their diagnosis is difficult, organic mental disorders and depression must be diagnosed and adequately treated to allow a real, personal and honest dialog. Administration of high doses of morphine is frequently used at the end of life not only to fully relieve pain but also to accelerate death, even if this is not clearly stated. This technique is not devoid of hypocrisy and high doses of morphine can have quite unpleasant side effects. Treatment withdrawal or withholding is generally not sufficient to allow a correct end of life. The arrest of ventilation, dialysis, artificial nutrition and even more hydration must often be coupled with techniques inducing unconsciousness, which makes imprecise the limits between such a "passive" ending of life and "active" euthanasia. The technique of terminal sedation, frequently based on the use of midazolam, has been more recently introduced in some palliative care units. Such a "controlled sedation" is supposed to allow a "natural" death by inducing a profound sleep. In opposition with active euthanasia, which allows a quiet and rapid death at a moment chosen by the patient himself, this technique of "sedation" has an undetermined duration, has legal implications which could be viewed as quite similar as the ones of euthanasia, and, moreover, this prolonged agony can be extremely stressful and distressing for the family. Medical-assisted suicide is allowed in The Netherlands under the same conditions as euthanasia. Death is generally obtained after a few hours but the technique is not always successful and the process of death can sometimes be prolonged and uncomfortable. This technique can nevertheless be preferred by some physicians and patients. As compared to active euthanasia, the proportion of medically-assisted suicides (1/6) is low in The Netherlands. Euthanasia is the only technique able to induce a peaceful and rapid death. The proportion of various techniques to actively induce death is probably quite similar in our country than in The Netherlands but, most of the time, these interventions occur at the very end of life when the patient is no longer able to participate in the decision process and thus occur without his explicit request. We think that, as for all medical decisions, the use of one or the other of these various techniques should be selected after a quiet and free discussion between the patient and his physician, preferably in advance and not in a situation of emergency and panic.