Implementing EBUS TBNA: first experience and review of literature.

Lung cancer has a very dismal prognosis and careful diagnosis and staging is of outmost importance. EBUS has become a cornerstone investigation for diagnosis and staging and current guidelines stress that there is a steep learning curve when introducing this tech- nique in practice (only 30 procedures are considered necessary). Over a period of 10 months a total of 21 patients have been addressed to our unit for an EBUS TBNA procedure. Only three were referred for staging purposes (for lung, digestive and cervix cancers) the others being primary diagnostic approaches where simpler procedures had previously failed. Procedures were initially performed under local anesthesia (3 cases) then under general anesthesia and jet ventilation using a laryngeal mask approach. Mediastinal lymph node group 7 was the most frequent target (9 cases) followed by group 4R (8 cases) and peribronchial tumoral processes (7 cases); one case did not required any needle-aspiration. On average each examination resulted in the sampling of 1.4 targets. There were no significant procedure related severe adverse events. Although 21 G cytology needles were used, adequate histological samples were obtained for 11 cases and cytology was the examination of choice for 9 cases. The pathology/cytology results were retrospectively assessed as satisfactory for 15 cases (confirmed neoplastic or other disease) and inconclusive for 5 cases. Non neoplastic disorders were represented by sarcoidosis, tuberculosis and bronchogenic cyst (3 cases). The procedure can be considered fast and safe; trained pathology personnel play an extremely important role: presently referrals are rare for staging purposes.

EGFR MUTATIONS IN NON-SMALL CELL LUNG CANCER: LOCAL EPIDEMIOLOGY AND CLINICAL IMPORTANCE.

INTRODUCTION: Lung cancer's dismal prognosis led to new therapeutic approaches among which TKIs being among most promising; MATERIAL AND METHOD: Retrospective study at the Regional Institute of Oncology Iasi of non small cell lung cancer patients which underwent molecular investigations between November 2013 - September 2014. EGFR mutation status (positive, negative, undetermined) was assessed with an Entrogen EGFR kit using DNA extracted from paraffin embedded samples (surgical or endobronchial biopsies) with the Macherey-Nagel "NucleoSpin FFPE DNAkit" and then amplified on a Applied Biosystem 7500 Real Time PCR System. RESULTS: There were 63 adenocarcinoma samples (17 females, mean age 60,9 +/- 9 years): 49 primary lung tumors and 14 secondary lesions (brain, lymph nodes, pleural). There was insufficient bioptic material for three cases. TTF1 status was determined for 46 patients--six were negative. There were twelve mutations identified (7 female subjects, 5 male)--six L858R, five Del 19 and one G719X; ten were TTF1 positive for the remaining two TTF1 status was unknown. Female sex predominance was statistically significant (p = 0.02, chi squared). Mean age for mutation positive patients was 64 +/- 10 years; there were three never smokers, three active smokers and no data on smoking status was available for six subjects. CONCLUSION: Although small dimension of the study group precludes statistical significance EGFR mutations seem to correlate with TTF1 status.

Clinical utility of diagnostic markers for malignant pleural mesothelioma.

Malignant mesothelioma has a very dismal prognosis with very few patients surviving one year after diagnosis. Early multimodal treatment, however, is expected to improve the outcome. Today, there is a strong need to have disease markers which could be used for screening, diagnosing, and/or monitoring tumour response to treatment. Old markers such as hyaluronic acid, various cytokeratin fragments (CYFRA 21.1, TPA) and other cancer antigens (CA 15.3, CA 125 or CA 19.9 or CEA) are not sensitive or specific enough and cannot be used in practice. More recently new molecules, such as soluble mesothelin and osteopontin, have been proposed for diagnostic purposes. Soluble mesothelin has a good specificity but has a sub-optimal sensitivity being negative in all sarcomatoid and in up to one half of epithelioid mesothelioma. On the contrary osteopontin has an inadequate specificity. Combining different markers together does not lead to an improvement in diagnostic accuracy. Neither marker can be used for screening purposes, the main limitation being the very low incidence of the disease in the at-risk, asbestos exposed population. Mesothelin is also a promising marker for monitoring response to treatment but published data is still insufficient to make recommendations. There is still a strong need for research is this area both in order to discover new markers as well as to correct the positioning of each existing molecule (alone or in combination) is the evaluation of the patients with a mesothelioma.

[Other thoracic cancers. Malignant pleural mesothelioma: biology and diagnosis]. / Mésothéliome pleural malin: biologie et diagnostic.

Malignant pleural mesothelioma (MPM) is a serious issue worldwide because of its increasing incidence and poor prognosis despite real recent improvements in the disease management. Most of the patients are diagnosed late in the course of the disease when radical treatment is no more an option. Therefore an earlier diagnosis of MPM is needed to significantly increase the survival of patients. Some soluble markers, including soluble mesothelin and osteopontin, have been previously proposed for MPM diagnosis but none has been validated yet. Soluble mesothelin, assessed in blood and in pleural effusion, seems to be the most promising candidate. However, even if it has a good diagnostic and prognostic value, it is quite specific for the epithelioid subtype, the most frequent one of mesothelioma, thus limiting its usefulness in practice. Despite sometimes a good sensitivity, other potential markers as osteopontin are of little interest for MPM diagnosis because of a low specificity. In conclusion, the present data do not justify the use of biology for MPM diagnosis in routine yet but rather suggest a need for a continuing evaluation of soluble mesothelin in clinical studies and the search for other potential tumor markers.

[Disseminated tuberculosis with severe multi- organ failure in a patient with AIDS]. / Tuberculose disséminée avec défaillance multiviscérale foudroyante au cours d'un sida.

INTRODUCTION: Tuberculosis is the most common infectious complication in HIV infected patients. The incidence of tuberculosis and the proportion of disseminated disease increase with more severe immuno-suppression. Septic shock and multiple organ failure are uncommon but are of markedly bad prognostic significance. CASE REPORT: A forty-four year old HIV seropositive man was admitted to the intensive care unit (ICU) with acute respiratory distress. The patient had been febrile for the previous two weeks. His thoracic radiograph showed a discrete interstitial infiltrate and at bronchoscopy small whitish granulations were observed in the main bronchi. All bacteriological investigations remained negative at the time of ICU admission. The patient died sixteen hours later due to multiple organ failure. Mycobacteria were identified after patient's death on the smear from BAL, from blood cultures, and in a postmortem liver biopsy. CONCLUSIONS: Septic shock is an infrequent complication of disseminated tuberculosis. Mortality is very high. Treatment should be started early in cases with a high diagnostic suspicion.

Tracheo-bronchial foreign bodies.

Suspicion of foreign bodies inhalation is a frequent problem in clinical practice. Despite the fact that the parents or the patients themselves easily notice symptoms, the delay in initiating diagnostic procedures is important. Delaying diagnosis and extraction results in potential severe complications. Diagnosis and treatment rely on invasive bronchoscopic procedures and therefore a careful designed standardized evaluation should be employed in order to decrease unnecessary bronchoscopies. Classical clinical signs of foreign body inhalation have low positive predictive values and every attempt to confirm or exclude the diagnosis should be done. Patients should be addressed to experienced centers for evaluation and treatment. Confirmation of the diagnosis should be done by flexible bronchoscopy. Extraction generally relies on rigid bronchoscopy, which seems to be more secured. Flexible bronchoscopy can also be used for extraction but rigid bronchoscopy should be always immediately available. Extraction failure rate and complications are rare in hands of experienced individuals and surgical removal is seldom necessary.

[Ultrastructural aspects in the development of the human heart. I. The cytoskeleton and motility of human embryonic myocardiocytes]. / Aspects ultrastructuraux dans le developpement du coeur humain. Note I: Le cytosquelette et la motilité des myocardocytes embrionaires humaines.

Electron microscopic investigations performed on heart tissue fragments from 12 human embryos. 8 to 15 weeks of age, showed that at the age of 8 weeks the myocardiocytes are poorly differentiated cells: they contain microfilaments of actin and myosin inserted on the cytoplasmic aspect of plasmalemma, a smooth endoplasmic reticulin and mitochondria, accounting for the early contraction. Gap junctions appear among myocardiocytes, confirming the myogenic theory of heart contractions. Within 10 to 15 weeks, actin and myosin myofilaments organize in sarcomeres. Eberth disks appear and numerous mitoses are to be seen.