Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions.

BACKGROUND: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected. RESULTS: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had <10 pg mutated genomes/µl with allelic fractions below 0.25%. Patients treated first line with TKIs based exclusively on EGFR positivity in blood had an ORR of 72% and a median PFS of 11 months. Of 105 patients screened after progression to EGFR-TKIs, sensitizing mutations were found in 56.2% and the p.T790M resistance mutation in 35.2%. CONCLUSIONS: Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

Treatment of drug-eluting stents in-stent restenosis with paclitaxel-coated balloon angioplasty: Insights from the French "real-world" prospective GARO Registry.

BACKGROUND: Data about paclitaxel-eluting balloon (PCB) angioplasty to treat drug-eluting stents (DES) in-stent restenosis (ISR) were mainly collected in selected patient populations in the setting of randomized trials. The main goal of this prospective registry was to confirm the positive findings of these studies in an unselected population in clinical practice. METHODS: Consecutive patients with DES-ISR treated by PCB angioplasty were recruited in this prospective real-world registry. The primary endpoint was clinically driven target-lesion revascularization (TLR) at 9 months. Secondary endpoints included acute technical success, in-hospital outcomes, 9-month major adverse cardiac events (MACE) a composite of death, myocardial infarction (MI) and TLR and the occurrence of target vessel revascularization. RESULTS: A total of 206 patients (67.7 ± 10.2 years, 80.6% male, 41.3% diabetics) with 210 lesions were recruited. Unstable coronary artery disease was present in 55.3% of patients. The time from DES implantation to DES-ISR was 3.0 ± 2.4 years. Quantitative analyses revealed that patterns of treated DES-ISR were focal in 55.7% and diffuse in 44.3%. The reference diameter was 2.76 ± 0.64 mm. The 9-month follow-up rate was 90.8% (187/206). At 9 months, the TLR rate was 7.0% (13/187) whereas the rates for MACE, MI and cardiac death were 10.7% (20/187), 4.8% (9/187) and 2.1% (4/187) respectively. Results were consistent in patients with paclitaxel and non-paclitaxel-eluting stents (PES) ISR. CONCLUSION: This large prospective registry demonstrated acceptable rates of TLR and MACE at 9 months after treatment of DES-ISR by PCB angioplasty. PCB angioplasty was equally effective in patients with PES-ISR and non PES-ISR.

SEOM clinical guidelines for the treatment of small-cell lung cancer 2013.

In this updated SCLC guidelines the authors have reviewed the "SEOM recommendation" for diagnosis and treatment of patients, including consideration for elderly and unfit patients. We hope the SCLC guidelines will be useful for residents and oncology teams.

[Role of angioplasty in the treatment of renal artery stenosis]. / Place de l'angioplastie des artères rénales.

Atherosclerotic renal artery stenosis is frequent and is associated with a high incidence of morbidity and mortality, with a strong correlation with coronary artery disease, (Kalra et al., 2005; Cheung et al., 2002; Guo et al., 2007 [1-3]). The atherosclerotic renal artery stenosis is an independent predictive factor of death (Conlon et al., 1998 [4]). The treatment of this lesion does not have strong evidence. A lot of studies in this area suggest the angioplasty is superior in a big majority between surgery, and angioplasty with stent is superior between balloon angioplasty, but some studies fail to prove the superiority of angioplasty versus medical treatment. These studies have sadly a lot of mistakes and nowadays we don't know what is the treatment for our patients in a lot of cases. The angioplasty is indicated when there is a failure of antihypertensive medications for control of blood pressure, when it is associated with a renal insufficiency quickly progressive or when there is a lesion on each renal artery. Other studies must be organized for prove the superiority of angioplasty when there is a real stenosis, maybe with the use of fractional flow reserve.

Identificación temprana de trastornos del lenguaje / Early identification of language disorders

El trastorno en el desarrollo del lenguaje es una de las manifestaciones que se observa con mayor frecuencia en el consultorio pediátrico. El hecho de hacer correcciones a tiempo de los problemas del lenguaje permite al individuo no sólo la capacidad para poder expresar todo su mundo interior, sino ayudan a mejorar la capacidad de automodulación de conductas así como la organización del pensamiento. Existen los llamados “periodos críticos” o “ventanas de oportunidad” y éstos se refieren a los periodos en que es posible adquirir ciertas habilidades o destrezas de manera natural, sencilla y perdurable. Si por alguna razón el pequeño perdió ese periodo crítico, no será capaz de utilizar esa habilidad tan bien como debería y no podrá aprenderla apropiadamente. La planificación del tratamiento incluye educación y entrenamiento de los padres, terapias de apoyo tempranas que van más allá de lenguaje, y el sistema motor es también muy importante. El personal de salud involucrado tiene múltiples roles en la prevención, detección, diagnóstico y manejo del niño con problemas de lenguaje.

The language disorders, is one of the most frequent manifestations seen in the pediatric office. The effect of early treatments in language problems impacts in the individual not only in their expression capacity but also in the behavioral modulation and in the thinking organization. The “critical periods” or “opportunity windows” are very important, and are those moments where it’s possible to acquire certain abilities in natural manner, simple and for all time. If for any reason the toddler lost these periods, it will impact in their form to use these capacities, and it’s possible to not acquire well. The treatment planification includes parent education and training, early therapy programs not only as language but to for motor system it´s very important. The personal health group has multiple rolls in prevention, detection, diagnosis and treatment in kids with language disorders.

[Pilot study of the efficacy of ticlopidine in early patency of coronary endoprostheses]. / Etude pilote de l'efficacité de la ticlopidine dans la perméabilité précoce des endoprothèses coronaires.

Subacute thrombosis of coronary stents is the main complication of this technique. The authors studied the outcome of 387 patients and 400 coronary arteries who underwent implantation of 427 stents between December 1989 and February 1994 and followed up one month after the procedure: all patients receive 500 mg of ticlopidine daily from three days before angioplasty throughout the hospital period and continued for at least one month. Anticoagulation with heparin was undertaken by the intravenous route after implantation and relayed with subcutaneous heparin for one week until control coronary angiography performed in the first 300 patients. At one month, 96.9% of patients were free of clinical coronary events. The following major complications were observed: 5 deaths (1.3%), 5 Q wave myocardial infarctions (1.3%); no emergency bypass surgery. The peripheral vascular complication rate was 3.6%. Univariate analysis three risk factors of subacute thrombosis: age (p = 0.0058), arterial diameter of less than 3 mm (p < 0.01) and implantation for occlusive dissection (p = 0.03). Multivariate analysis showed two independent risk factors: age (p = 0.001) and arterial diameter of less than 3 mm (p = 0.01). This pilot study shows a particularly low subacute thrombosis rate in unselected indications with an acceptable level of vascular complications.

[Post-traumatic fistula of the left anterior descending coronary artery and left ventricle. Apropos of a new case]. / Fistule post-traumatique entre l'interventriculaire antérieure et le ventricule gauche. A propos d'un nouveau cas.

The authors report the case of a 23 year old man who presented with a continuous murmur five years after closed chest trauma. The electrocardiographic and echocardiographic findings indicated previous apical myocardial infarction. The underlying diagnosis was first suggested by continuous wave Doppler which showed systolo-diastolic flow in the septo-apical region directed towards the left ventricle (LV) in diastole. Color Doppler flow studies showed a mosaic pattern opposite a dilated left anterior descending (LAD) artery. These signs of LAD-LV fistula with a single orific were confirmed at coronary arteriography. The patient's previous history was in favour of a traumatic etiology. In the absence of left ventricular failure and myocardial ischaemia by coronary steal, surgery was deferred; Doppler echocardiography would seem to be a good method of following up the fistula and its consequences on left ventricular function. A traumatic left coronary to left ventricular fistula is an extremely rare condition and merits publication. The authors review the literature and describe the physiopathology, diagnosis and therapeutic indications of these fistulae.

[Percutaneous coronary transluminal angioplasty with extracorporeal circulation: preliminary results]. / Angioplastica coronarica percutanea transluminale con assistenza circolatoria extracorporea: risultati preliminari.

Percutaneous transluminal coronary angioplasty (PTCA) in patients with low ejection fraction (EF) and/or a large area of remaining viable myocardium served by the target vessel can cause hemodynamic collapse in case of acute closure. We report 11 patients in whom the cardiopulmonary bypass support (CPS) was instituted because of contraindication to surgery (Group I) or unstable angina associated with low EF and/or a large amount of myocardium perfused by the target artery (Group II). Nine were male and 2 female, mean ages of 70, with Canadian angor class I (1), II (1), or IV (9) and EF ranging from 12 to 65% (mean 34%). Thirty were the lesions to dilate; 28 were dilated successfully; in 2 an aortic dilation was also performed. One death occurred after the procedure related to collapse due to hypovolemia; another death occurred 8 months after PTCA because of pulmonary neoplasia. The other 9 patients followed-up at 1 to 8 months (mean 3.9) disclosed Canadian angor class I. The procedure's technique and the related complications are discussed. We conclude that cardiopulmonary bypass support can be used safely in patients refused to surgery and with high risk PTCA; such a procedure may expand the indication of PTCA.

[Atrioventricular block, a complication of radiotherapy of the mediastinum]. / Bloc auriculo-ventriculaire, complication de la radiothérapie du médiastin.

Cardiac complications of mediastinal irradiation usually concern the pericardium, the ventricular myocardium and the coronary arteries. We report the case of a 42-year old woman who experienced a syncopal atrioventricular (AV) block 12 years after irradiation of a mediastinal Hodgkin's lymphoma. Electrophysiological recordings showed infranodal conduction disturbances. A review of the literature yielded only 12 cases of syncopal radiation-induced AV block. This case highlights the risk of syncopal AV blocks occurring a long time after mediastinal irradiation and leading to severe damage of the His bundle and its branches. The presence, as in our patient, of an associated right ventricular outflow tract stenosis confirms the importance and severity of radiation-induced cardiac lesions.

Valoración aminérgica en pacientes con tumor hipofisiario productor de prolactina / Valoration aminergic in patients with hypophyseal prolactin producing tumors

Se estudia la importancia de las teorías etiológicas actuales de los tumores productores de prolactina (PRL). Así, los tumores productores de PRL pueden considerarse como un síndrome de múltiples etiologías, en las que participan diferentes estímulos peptidérgicos hipotalámicos. En pacientes con diagnóstico de tumor productor de PRL se estudiaron: A) la regulación dopaminérgica que estimula o inhibe la secreción de PRL, B) la neurotransmisión gabaminérgica que tambien estimula la secreción de PRL en el sistema nervioso central y lactotropo hipofisiario; y C) la vía serotoninérgica que produce liberación de PRL. Estos tipos de estímulos pueden ser la causa subyacente de la hiperplasia celular que origina la secreción de PRL .