Ustekinumab in bio-naïve and bio-failure Crohn's disease patients: Results from a « real-life ¼ monocentric cohort.

BACKGROUND: The pivotal clinical trials have largely demonstrated the efficacy and safety of ustekinumab in Crohn's disease. Real-life cohorts published so far only include very few bio-naïve patients. This study assesses effectiveness and safety of ustekinumab in bio-naïve and bio-failure patients treated with ustekinumab in routine practice and look for predictors of response. METHODS: We performed a retrospective monocentric study. Initial response was assessed by maintenance therapy beyond week 16. Sustained response was assessed by the continuation or cessation of therapy over time for another reason than stopping in sustained remission. Treatment persistence was assessed by Kaplan Meier curves and predictors of treatment persistence were studied by univariate and multivariate Cox model. RESULTS: Out of 156 recorded patients, three patients were still in their induction phase at time of analysis and 5 patients were lost to follow-up, leaving 148 patients for clinical effectiveness analyses, including 35 bio-naïve when starting ustekinumab. A maintenance therapy was initiated in 79.7%. At one year, the probability to be still treated with ustekinumab was 73.8%. Treatment cessation increased with smoking in multivariate analysis. Previous biologic failure (as a whole), CRP and fecal calprotectin baseline levels did not influence initial response and treatment persistence. CONCLUSION: A large proportion of CD patients initially respond to ustekinumab and continue this treatment beyond one year. Treatment persistence is as high in bio-failure as in bio-naïve patients.

WITHDRAWN: A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

The article has been withdrawn at the request of the authors and editor because of incorrect authorship, which is considered a form of unethical publication. The Publisher apologizes for any inconvenience this may cause.

[Comprehensive therapeutic strategy for localized esophageal cancer. Second part : interest of multimodal approaches with or without surgery]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 2ème partie : l'intérêt des approches multimodales avec ou sans chirurgie.

In recent years, the treatment of esophagus cancer has been completely changed, thus competing the dogma of surgery as the cornerstone treatment. Multimodality treatments as radio-chemotherapy directly followed by surgery, or delayed surgery, significantly improve patient survival compared to surgery alone. Neoadjuvant radiochemotherapy is associated with a higher complete pathologic response rate and improved survival compared to chemotherapy alone. Immediate surgery after radio-chemotherapy is challenged for patients who present a complete clinical response, especially in case of squamous cell carcinoma. Indeed, systematic resection is associated with a significant postoperative mortality rate and has not proven any survival advantage in complete clinical responders as opposed to delayed resection in case of locally persistent or recurrent disease. In squamous cell carcinoma, this could lead to organ preservation, thus avoiding the mortality and durable functional impairment of esophagectomy. This review will discuss the positioning of the multimodality treatment strategy with neoadjuvant radiochemotherapy and chemotherapy and also the strategy of organ preservation.

Depuis quelques années, le traitement du cancer de l'œsophage est en pleine mutation, bousculant ainsi le grand dogme de la chirurgie comme pierre angulaire du traitement. Par rapport à la chirurgie seule, les traitements multimodaux de radiochimiothérapie suivis, directement ou de façon différée, par la chirurgie améliorent significativement les chances de survie prolongée des patients. Comparée à la chimiothérapie néodjuvante, la radiochimiothérapie néoadjuvante démontre un taux de réponse pathologique complet plus élevé qui résulte en une survie prolongée. Chez les très bons répondeurs cliniques, la question de la place de la résection chirurgicale d'emblée est remise en question, surtout pour les carcinomes épidermoïdes. Chez ces patients, la résection systématique par rapport à un acte différé n'offre pas d'avantage en survie, expose le patient à un risque de mortalité significatif alors qu'un certain nombre de patients n'auront jamais à être opérés. Le seul bénéfice actuellement démontré de la résection est une amélioration du contrôle local; or, le devenir du patient est principalement lié à la récidive métastatique. Dans cette revue, nous positionnons et discutons la place des différents traitements multimodaux, chimiothérapie et radiochimiothérapie néoadjuvantes, ainsi que la place de la préservation d'organe par rapport à une chirurgie d'emblée après une radiochimiothérapie.

[Comprehensive therapeutic strategy for localized esophageal cancer]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 1ère partie : le point sur les approches chirurgicales et non chirurgicales.

Esophageal cancers represent a highly heterogeneous entity mixing two different tumour types : AdenoCarcinoma (ADC) and Squamous Cell Carcinoma (SSC). Developing in the same organ, they are very often considered as a unique pathology and, consequently, the same therapeutic strategy is indiscriminately applied. Esophageal cancer treatments are particularly complex and require a multidisciplinary approach. Despite impressive advances in the tumour statidifaction, surgery, radiotherapy and chemotherapy, the overall prognosis remains grim even at an early stage of the disease. In order to improve the treatment of esophageal cancers and the patient’s survival, we need to consider that ADC and SCC represent two different pathologies requiring specific therapeutic strategies. This review in two parts will present recent data from clinical trials under the scope of tumour histology to set up dedicated therapeutic strategies. In this first part, we explain the restricted role of surgical resection, the prognostic factors and the results of exclusive combined chemotherapy and radiation in localized esophageal cancer.

Les cancers de l'œsophage concernent deux entités d'histologie et de pathogenèse différentes : les carcinomes épidermoïdes (CE) et les adénocarcinomes (ADC). Ils se développent dans un même organe et sont souvent considérés comme une seule et unique maladie avec, comme conséquence, une stratégie thérapeutique identique. Leur traitement est complexe et requiert une prise en charge multidisciplinaire. Bien que les techniques de mise au point de la pathologie, de traitement par chirurgie, de radiothérapie et de chimiothérapie se soient améliorées, le pronostic de la maladie reste péjoratif, même à un stade précoce. L'amélioration de la prise en charge et de la survie des patients nécessite de considérer les CE et les ADC comme deux pathologies distinctes, impliquant des approches thérapeutiques qui leur soient spécifiquement dédiées. Cette revue en deux parties analyse les différents aspects thérapeutiques des cancers de l'œsophage sous l'angle de l'histologie et permet de dégager des stratégies spécifiques. Cette première partie est consacrée aux limites de la résection chirurgicale, aux facteurs pronostiques et aux résultats des traitements par radio-chimiothérapie exclusive des cancers localisés.

A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

BACKGROUND AND STUDY AIMS: The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature. PATIENTS METHODS: We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups. RESULTS: For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively. CONCLUSIONS: Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.

[Evolution in the therapeutic strategy of localized resectable pancreatic ductal adenocarcinoma]. / Evolution dans la prise en charge de l'adénocarcinome du pancréas localisé estimé résécable.

Pancreatic ductal adenocarcinoma is characterized by a high rate of early metastatic relapse. Surgical resection is still recognized as the cornerstone upfront therapy. However, reported 5 years survival rates are inferior to 20-25% even when surgery is followed by chemotherapy. Margins involvement on the surgical specimen (50 to 85%) and lymph node involvement (around 70%) both strongly impact survival. Median survivals are close to those of locally advanced diseases treated by chemotherapy or chemoradiotherapy, 15 to 16 months. This review focuses on adverse prognostic factors, post-operative outcomes and their impact on multimodality therapy completion rates and survivals in patients undergoing upfront surgery. Current data and emerging results from neoadjuvant series could lead to a change in the therapeutic strategy.

[CRITICAL VIEWPOINT ON THE CURRENT APPROACH OF LOCALIZED PANCREATIC DUCTAL ADENOCARCINOMA]. / COMMENT JE TRAITE ... Point de vue critique sur l'approche actuelle du cancer du pancréas localize.

Surgical resection followed by chemotherapy is the actual standard of care for localized, deemed resectable, pancreatic ductal adenocarcinoma. Despite a better selection of surgical candidates and the actual performance of expert teams, the proportion of patients with a prolonged survival has not been ameliorated during the last three decades. The morphological determinants of resectability are the subject of limitations. In the future, only a better understanding of the biological process, an earlier diagnosis of purely localized disease and more efficient systemic therapies may lead to a better prognosis. Meanwhile, taking into account the prognostic factors associated with a lower chance of cure is currently a matter of debate. The optimal therapeutic sequence, being a surgery-first or a neoadjuvant approach is controversial. The theoretical advantages of preoperative chemotherapy eventually associated with chemo-radiation are demonstrated in other tumours and applicable to pancreatic cancer without any excess of operative mortality, early progression rates and, on the contrary with positive survival data. The completion rates of multi-modal therapy are in favour of the preoperative approach, which also gives the opportunity to select the best candidates for surgical resection.

[Lynch syndrome and microsatellite instability: a review]. / Le syndrome de Lynch et l'instabilité des microsatellites: revue de littérature.

Microsatellite instability (MSI) phenotype occurs in approximately 15 to 24% of colorectal cancer (CRC) patients and may be sporadic or hereditary. It reflects a mutator phenotype in the tumor due to a lack of mismatch repair system. MSI is indeed one of the characteristics of CRCs occurring in Lynch syndrome and some sporadic cases. CRCs with MSI have a better prognosis than CRCs with microsatellite stability (MSS). This is explained partly by a more important anti-tumor immune response and by apoptosis of tumor cells in which mutations accumulate. However, in some retrospective studies, microsatellite instability in stage II CRCs was associated with no benefit to or even a deleterious effect of 5-FU alone based adjuvant therapy. Nevertheless, results obtained in stage III CRCs with FOLFOX type adjuvant chemotherapy remain favorable in retrospective studies.

Esophageal cancer surgery in patients older than 75: long term results.

PURPOSE: The purpose of this study was to evaluate short and long term results after esophageal cancer resection in patients older than 75. METHODS: We retrospectively analyzed the database of esophageal cancer surgically treated in our department between January 2003 and December 2009 to identify patients older than 75. The preoperative, operative, postoperative and long term characteristics were analyzed. RESULTS: Among 137 patient, 23 were older than 75. The histological subtype was adenocarcinoma in 100%. The surgical techniques were a "Lewis-Santy" procedure in 43%, a trans-hiatal resection in 22%, a "Sweet" procedure in 13%, a stripping in 13% and a McKeown procedure in 9%. The in-hospital postoperative mortality was 13%. The in-hospital postoperative morbidity (Dindo-Clavien Grade >2, deceased patients included) was 26%. In univariate analysis, no statistically significant risk factor of morbidity was found. A Charlson Comorbidity Index >2 was, in univariate analysis, the sole risk factor of postoperative mortality (p = 0.0362). The mean hospital stay was 22 +/- 12 days. The median survival was 24.2 months. The 5-year overall survival was 39% and the 5-year disease free survival was 26%.57% of long-term deaths were not cancer related. CONCLUSION: Esophageal surgery performed in selected patients older than 75 has an acceptable morbidity and mortality but when a severe complication occurs, it leads to death in half of the cases. Surgery enables a long term survival benefit. This study confirmed our attitude of not considering age as a contra-indication for esophageal surgery but rather considering general status, self-reliance and associated comorbidities for patients' selection.

Amygdala connections with jaw, tongue and laryngo-pharyngeal premotor neurons.

As the central nucleus (CE) is the only amygdaloid nucleus to send axons to the pons and medulla, it is thought to be involved in the expression of conditioned responses by accessing hindbrain circuitry generating stereotypic responses to aversive stimuli. Responses to aversive oral stimuli include gaping and tongue protrusion generated by central pattern generators and other premotor neurons in the ponto-medullary reticular formation. We investigated central nucleus connections with the reticular formation by identifying premotor reticular formation neurons through the retrograde trans-synaptic transport of pseudorabies virus (PRV) inoculated into masseter, genioglossus, thyroarytenoid or inferior constrictor muscles in combination with anterograde labeling of CE axons with biotinylated dextran amine. Three dimensional mapping of PRV infected premotor neurons revealed specific clusters of these neurons associated with different oro-laryngo-pharyngeal muscles, particularly in the parvicellular reticular formation. CE axon terminals were concentrated in certain parvicellular clusters but overall putative contacts were identified with premotor neurons associated with all four oro-laryngo-pharyngeal muscles investigated. We also mapped the retrograde trans-synaptic spread of PRV through the various nuclei of the amygdaloid complex. Medial CE was the first amygdala structure infected (4 days post-inoculation) with trans-synaptic spread to the lateral CE and the caudomedial parvicellular basolateral nucleus by day 5 post-inoculation. Infected neurons were only very rarely found in the lateral capsular CE and the lateral nucleus and then at only the latest time points. The data demonstrate that the CE is directly connected with clusters of reticular premotor neurons that may represent complex pattern generators and/or switching elements for the generation of stereotypic oral and laryngo-pharyngeal movements during aversive oral stimulation. Serial connections through the amygdaloid complex linked with the oro-laryngo-pharyngeal musculature appear quite distinct from those believed to sub-serve fear responses, suggesting there are distinct "channels" for the acquisition and expression of particular conditioned behaviors.

[Clinical case of the month. Cystic lymphangioma of the mesentery]. / Le cas clinique du mois. Le lymphangiome kystique du mésentère.

Cystic lymphangioma of the mesentery is a benign condition, probably of malformative origin, and frequently appearing in infancy. Its symptomatology can be very polymorphic. Its diagnosis is suspected by ultrasonography and computed tomography, and definitely confirmed by pathology. About a recent case of cystic lymphangioma of the mesentery diagnosed and operated on at the university hospital of Liège in an adult patient, the authors review its classification and its therapeutic strategy. Surgical resection is indicated in symptomatic cystic lymphangioma.

Surgical management of hepatic metastases of colorectal origin.

Colorectal cancer is the most frequent digestive cancer. Prognosis is greatly depending on the TNM stage at the time of diagnosis. Fifty percent of all patients shall develop, synchronously or metachronously, liver metastases. Different means such as chemotherapy, targeted therapies, radiofrequency ablation, portal vein embolization and two-stage hepatectomy may be used to make these metastases eventually resectable and to increase overall survival. This is a short review of these different methods used to increase resectability but also on the integration of these parameters in a larger approach of colorectal liver metastasis surgery especially insisting on multidisciplinary discussion.

[Monoclonal antibodies therapies for colorectal cancer: cétuximab, panitumumab and bevacizumab]. / Apports des anticorps monoclonaux dans le traitement du cancer colorectal: cétuximab, panitumumab et bévacizumab.

Colorectal cancer is the third most common form of cancer in Europe, Its prognosis is poor, since median survival time for metastatic patients is about 20 months. Progresses in molecular biology have lead to significant improvement in the management of metastatic colorectal cancer with targeted therapies. The monoclonal antibodies anti-EGFR and anti-VEGFR improve the overall and the progression-free survival. The anti-EGFR antibodies (cétuximab and panitumumab) have been marketed in Belgium, as monotherapy or in association with chemotherapy (FOLFIRI) for third line use in patients with wild type K-ras. The anti-VEGFR bevacizumab is the standard first line treatment in metastatic colorectal cancer with irinotecan based chemotherapy. For the future, the place of monoclonal antibodies therapies in adjuvant or in first line settings and the value of combining targeted therapies have to be further defined.

[Treatment of (unresectable) hepatocellular carcinoma at an intermediate or advanced stage]. / Straitement des carcinomes hépatocellulaires à un stade intermédiaire ou avancé.

Hepatocellular carcinoma is the main primitive tumor of the liver. It occurs in the setting of liver cirrhosis in more than 90% of the cases in developing countries. The prognosis depends on the size, number and extension of the tumor as well as on the severity of the underlying liver disease. The Barcelona Clinic Classification takes into account these different parameters and helps the clinician in the therapeutic decision. Some patients (around 25%) are amenable to therapy with a curative intent (liver transplantation, resection, destruction by radiofrequency). In patients with hepatocellular carcinoma at an intermediate stage, lipiodolized chemoembolization gives a survival advantage in comparison with placebo. No conventional regimen of chemotherapy has a proven survival benefit. In patients with a hepatocellular carcinoma at an advanced stage, sorafenib, an oral multi-targeted kinase inhibitor, is the first compound to demonstrate a significant effect on survival free of disease progression in a selected group of patients. Its toxicity profile is particularly favourable. Combination of surgical and medical therapies should be properly evaluated in clinical trials in the near future.

[Palliative management of hepatocarcinoma with sorafenib (Nexavar). Results of the SHARP study (sorafenib hepatocarcinoma assessment randomized protocol trial)]. / L'étude clinique du mois traitement de l'hépatocarcinome au stade palliatif par sorafénib (Nexavar). Résultats de l'étude SHARP (sorafenib hepatocarcinoma assessment randomized protocol).

Curative management of early-stage hepatocarcinoma may include partial hepatic resection, liver transplantation or tumoral necrosis using radiofrequency ablation or alcoholisation. Until recently, no efficient therapeutic mean was available for advanced hepatocarcinoma. Sorafenib (Nexavar, Bayer) is a multikinase inhibitor that decreases tumoral proliferation and angiogenesis, and increases apoptosis in many cancer models. The results of a phase 3 randomized, multicentric, study, entitled SHARP, have now demonstrated that sorafenib increases survival in patients with advanced hepatocarcinoma developed in Child A cirrhosis. Mean survival gain was a little less than 3 months, without any radiologic response or improvement in the delay before symptomatic progression of the disease. The monthly cost of sorafenib is a little more than 5,000 euros. It is now crucial to evaluate the potential role of sorafenib in adjuvant therapy after liver resection or radiofrequency ablation of hepatocarcinoma. The CHU of Liège is taking part to a randomized, multicentric study evaluating the use of sorafenib after liver resection or radiofrequency ablation for hepatocarcinoma. Another future evaluation could be the association of sorafenib with other antitumoral agents.

Multiple forebrain systems converge on motor neurons innervating the thyroarytenoid muscle.

The present study investigated the central connections of motor neurons innervating the thyroarytenoid laryngeal muscle that is active in swallowing, respiration and vocalization. In both intact and sympathectomized rats, the pseudorabies virus (PRV) was inoculated into the muscle. After initial infection of laryngomotor neurons in the ipsilateral loose division of the nucleus ambiguus (NA) by 3 days post-inoculation, PRV spread to the ipsilateral compact portion of the NA, the central and intermediate divisions of the nucleus tractus solitarii, the Botzinger complex, and the parvicellular reticular formation by 4 days. Infection was subsequently expanded to include the ipsilateral granular and dysgranular parietal insular cortex, the ipsilateral medial division of the central nucleus of the amygdala, the lateral, paraventricular, ventrolateral and medial preoptic nuclei of the hypothalamus (generally bilaterally), the lateral periaqueductal gray, the A7 and oral and caudal pontine nuclei. At the latest time points sampled post-inoculation (5 days), infected neurons were identified in the ipsilateral agranular insular cortex, the caudal parietal insular cortex, the anterior cingulate cortex, and the contralateral motor cortex. In the amygdala, infection had spread to the lateral central nucleus and the parvicellular portion of the basolateral nucleus. Hypothalamic infection was largely characterized by an increase in the number of infected cells in earlier infected regions though the posterior, dorsomedial, tuberomammillary and mammillary nuclei contained infected cells. Comparison with previous connectional data suggests PRV followed three interconnected systems originating in the forebrain; a bilateral system including the ventral anterior cingulate cortex, periaqueductal gray and ventral respiratory group; an ipsilateral system involving the parietal insular cortex, central nucleus of the amygdala and parvicellular reticular formation, and a minor contralateral system originating in motor cortex. Hypothalamic innervation involved several functionally specific nuclei. Overall, the data imply complex CNS control over the multi-functional thyroarytenoid muscle.

Hereditary angio-edema involving the gastrointestinal tract: CT findings.

We report a case of hereditary angio-edema in a young man presenting with recurrent abdominal pain for many years. The diagnosis was suspected on the basis of abdominal CT performed during an abdominal attack and was then confirmed by the measurement of serum concentration of C1 esterase inhibitor (C1-INH). To our knowledge, this is the first case reported of the hereditary form of angio-edema with isolated abdominal pain and in which the diagnosis was suggested by abdominal CT findings.

Oxaliplatin combined to 5-fluorouracil and folinic acid: an effective therapy in patients with advanced colorectal cancer.

Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)-containing regimen were eligible. One treatment cycle consisted of repeated administrations of 5-FU combined to folinic acid for six times and to oxaliplatin for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v. folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A total of 37 patients were treated according to this schedule. The rates of objective responses after the first and second treatment cycles were 28 and 17%, respectively, with rates of tumor growth control, i.e. including the stabilizations, of 55 and 28%. The median duration of response was 10 months and the median duration of stabilizations was 6 months. The median survival time from initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median survival time from the diagnosis of metastatic disease is 24 months (2-40+). The main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful therapy after failure of a previous 5-FU-containing treatment.

Laryngeal activity during swallow, phonation, and the Valsalva maneuver: an electromyographic analysis.

To better understand the mechanisms of airway protection during swallow, the authors of this study performed an electromyographic (EMG) analysis on the thyroarytenoid (TA) and interarytenoid (IA) muscles during a variety of tasks. The tasks included high, low, and comfortable pitch phonation, the Valsalva maneuver, saliva swallow, and 5- and 10-mL water swallows. Raw EMG signals were analyzed to obtain root mean square data, which correspond to a relative magnitude of muscle activation. The data show that both TA and IA muscles generate a similar level of relative activation, with the greatest electrical activity observed during swallow tasks followed by the Valsalva maneuver and phonation. The duration, onset, offset, and pattern of activity during the swallowing tasks also showed close synchronization between the two muscles. These data can be used in designing therapy for voice disorders and pharyngeal dysphagia.

[Federal Department of Health and Environment and its connection with the Academy of Medicine at Belgian and international levels]. / Het federaal departement van Volksgezondheid en Leefmilieu en zijn banden met de Academie voor Geneeskunde op belgisch en internationaal niveau.

Point of departure of the lecture is the note "Activities of the Royal Academy of Medicine of Belgium", written by professor Lacquet on 15 April 1994, in which he outlines the statutory links of the Academy with the federal administration. After having questioned the truly federal status of the National Foundation for Scientific Research and the Foundation for Medical Scientific Research, the links between the Academy and the federal ministry of Health are reaffirmed by the author with regard to the matters enumerated in article 2 of the statutes of the Academy. Subsequently the author discusses the international treaties and relations with its ensuing obligations for the ministry of Health. The obligations are in many cases shared with the Communities and the Regions. The author mentions: the bilateral agreements with regard to health care and medical sciences, concluded with twelve countries, the BENELUX, the European Union, NATO, the European Council and the WHO. In conclusion the author stresses that there remain only few formal links between the Academy and the federal ministry of Health, but that functional relations concerning important health matters still exist.