Rôle du pathologiste dans la prise en charge des tumeurs stromales gastro-intestinales (GIST) [The role of the pathologist in the management of gastrointestinal stromal tumors (GIST)]

Considerable progress was realized these last years in the understanding of the molecular mechanisms and the treatment of the GIST. Their diagnosis remains based on the morphology and immunohistochemistry. The evaluation of GIST prognosis was till know difficult to establish but a new histopronostic classification currently used allows a better therapeutic approach. The search for KIT and PDGFRA mutations is recommended to adapt a targeted therapy by KIT inhibitors. The pathologist plays a crucial role in the management of the GIST because it is on him that is based the diagnosis, the evaluation of the prognosis and the treatment (surgery and kit inhibitors).

Prise en charge du carcinome hépatocettulaire en 2010 [Management of hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.

Prise en charge des sténoses carotidiennes [Management of the carotid artery stenosis].

In the western world, the carotid-artery stenosis is one of the major causes of ischemic stroke in elderly people. The principal therapeutic indication is a symptomatic stenosis > 50% in the first two weeks and the surgical approach has shown the best results. Despite inferior results to carotid endarterectomy in terms of post-operative rate of stroke and/or death, except for young patients, carotid stenting remains the best choice in patients at high surgical risk. The best medical treatment, consisting in correction of cardiovascular risk factors, statin therapy and anti-aggregation led to a drastic reduction in the annual rate of stroke associated to carotid stenosis and thus limited the surgical intervention in asymptomatic patient to men with a life expectancy of at least 5 years and a stenosis > 70%.

Carcinomes épidermoïdes de l'hypopharynx et du larynx : prise en charge fondée sur les preuves Squamous cell carcinoma of the hypopharynx and larynx: evidence-based care.

Les carcinomes épidermoïdes de l'hypopharynx et du larynx peuvent être traités par chirurgie et/ou radiothérapie en fonction de la taille tumorale. Pour les petites tumeurs, les résultats sont équivalents. Pour les tumeurs localement avancées, l'approche chirurgicale est mutilante et nécessite une (pharyngo)laryngectomie totale. La chimioradiothérapie exclusive a montré tout son intérêt mais au prix de séquelles tardives. Dans le but de diminuer ces séquelles et les mutilations, la chimiothérapie d'induction par cisplatine, docétaxel et 5FU à visée de préservation d'organe devient le standard de traitement mais il manque des études solides de comparaison de cette approche avec la chimioradiothérapie exclusive. Il n'est pas possible de conclure quant à la supériorité d'un schéma en survie globale. Quand la chimiothérapie d'induction est choisie, les modalités de potentialisation éventuelle de la radiothérapie ne sont pas établies. Squamous cell carcinomas of larynx and hypopharynx can be treated by surgery and/or radiotherapy according to tumor size. For small tumors, the results are similar. For locally advanced tumors, the surgical approach is mutilating and requires a total (pharyngo)laryngectomy. Exclusive chemoradiotherapy has shown its interest at the cost of late sequelae. In order to reduce these effects and mutilation, induction chemotherapy with cisplatin, docetaxel and 5FU for organ preservation becomes the standard treatment but there are no solid studies comparing this approach with the exclusive chemoradiotherapy. And it is not possible to conclude as to the superiority of a scheme in terms of overall survival. When chemotherapy is chosen, the modalities of any potentiation of radiation have not been yet established.

Réplication cérébrale du VIH malgré une thérapie antirétrovirale efficace: impact clinique et prise en charge [Intracerebral HIV replication despite an efficient antiretroviral treatment: clinical impact and management].

Various neurological and neuropsychological manifestations are still relatively frequently reported in HIV infected patients in the highly active antiretroviral therapy era. A fraction of them could be related to HIV replication in the central nervous system (CNS) despite adequate peripheral viral suppression. This hypothesis is supported by numerous reports of detectable HIV RNA in the cerebrospinal fluid in the context of a low or undetectable viremia in association with neurological or neuropsychological complaints. In addition, some antiviral molecules may not achieve adequate levels in the CNS, thus potentially favoring intracerebral HIV replication and even antiretroviral resistance. Neurologic manifestations in the presence of CNS HIV replication often decrease after antiretroviral treatment CNS penetration optimization.

Infarctus myocardique aigu: importance du "networking" dans la prise en charge initiate [Acute myocardial infarction: importance of the networking in the initial management].

Early reperfusion with prompt re-establishment of coronary blood flow improves survival in patients suffering from acute ST-elevation myocardial infarction (STEMI). Leaving systemic thrombolysis for primary percutaneous coronary intervention (PCI) is justified by clinical results in favor of PCI. Nevertheless, primary PCI necessitates additional transfer time and requires an efficient territorial networking. The present article summarizes the up-to-dated management of patients with acute STEMI and/or overt cardiogenic shock.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.

BACKGROUND: Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients. METHODS: We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals. FINDINGS: Over 157,912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1.90, 95% CI 1.47-2.45 [p=0.0001] with abacavir and 1.49, 1.14-1.95 [p=0.003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1.49, 1.14-1.95 [p=0.004] with didanosine; 1.89, 1.47-2.45 [p=0.0001] with abacavir). INTERPRETATION: There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.

Prise en charge de la pneumonie communautaire [Management of community acquired pneumonia]

Une grande partie des patients présentant une pneumonie communautaire ont un bon pronostic et peuvent être suivis dans la pratique ambulatoire moyennant un nombre limité d'examens paracliniques. Le diagnostic repose sur une clinique suggestive en présence d'un infiltrat compatible avec une pneumonie à la radiographie de thorax. Une anamnèse de voyage et une bonne connaissance de résistances locales du pneumocoque aux antibiotiques sont déterminantes pour le choix du traitement. Pour les patients de moins de 50 ans sans comorbidités et sans signes de sévérité, il est généralement recommandé de prescrire un macrolide ou une fluoroquinolone de 3e ou de 4e génération (fluoroquinolones «respiratoires»). Pour les patients plus âgés, et pour ceux qui présentent des comorbidités ou des critères de sévérité, une évaluation à l'hôpital est indiquée. La majorité des patients hospitalisés en soins généraux peuvent être traités par l'association d'une bêta-lactame et d'un macrolide, ou par une fluoroquinolone «respiratoire» seule, après prélèvements d'expectorations et de sang pour culture.

Tumeurs de l'appareil locomoteur: de la simple "bosse" a la prise en charge multidisciplinaire [Tumors of the musculoskeletal system: from the "lumps" to multidisciplinary care].

Management of musculoskeletal tumours usually begins with the appearance of a lump or bump, or the onset of unspecific symptoms. A poor initial work-up, a faulty biopsy or an inadequate resection may have a severe impact on the prognosis, including re-interventions, amputation, local recurrence or systemic spread of the disease. The patient with a suspicious lesion should be referred to a "sarcoma centers" where a planned and well-performed diagnostic work-up will allow a precise diagnosis in terms of histology and staging. After a multidisciplinary discussion of the case, an accurate treatment plan is established. Such an approach allows an adequate patient management, often with a positive impact on the survival and functional outcome.

Nouveaux aspects de la prise en charge de l'hypertension artérielle chez le patient insuffisant rénal chronique [New aspects of hypertension management in patients with chronic kidney disease].

Hypertension is a frequent finding in patients with chronic kidney disease. Whether primary or secondary to renal disease, hypertension remains an important risk factory for the progression of chronic kidney disease and the occurrence of cardiovascular events. The objective of this paper is to review different treatment strategies in hypertensive CKD patients, with the exclusion of patients with renal replacement therapy such as dialysis or renal transplantation.

Bypass gastrique: prise en charge des complications et désagrements alimentaires [Gastric bypass: management of complications and food tolerance]

La chirurgie bariatrique est le seul traitement qui permette une perte pondérale significative sur le long terme mais le succès d'une telle intervention repose avant tout dans une sélection et une préparation attentive du patient. Une bonne connaissance des implications de l'opération permet de favoriser un changement de comportement alimentaire et par là aussi de diminuer les complications et les désagréments alimentaires. L'éducation du patient n'a de sens que si elle s'inscrit dans une prise en charge pluridisciplinaire, comprenant également un suivi diététique, planifié sur le long terme. La mastication, la vitesse d'ingestion des aliments, le fait de renoncer aux boissons gazeuses et de devoir boire régulièrement entre les repas, sont les éléments les plus difficiles à mettre en place pour le patient. Bariatric surgery is the only treatment inducing effective weight loss on the long term. The success of such an intervention is possible by carefully selecting and educating the candidates. Good understanding of the bariatric surgery implications allows the patients to modify their eating habits and thus decrease complications and food intolerance. Therefore patient education requires a multidisciplinary approach which implies the follow-up of a dietician on the long term. Mastication, speed of food ingestion, avoidance of carbonated beverages as well as the obligation to drink at frequent and regular intervals are the most difficult aspects to be taught to the patients

Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors.

BACKGROUND: Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs. METHODS: The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response. RESULTS: One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively. CONCLUSIONS: Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted.