Next generation sequencing in synovial sarcoma reveals novel gene mutations

Over 95% of all synovial sarcomas (SS) share a unique translocation, t(X;18), however, they show heterogeneous clinical behavior. We analyzed multiple SS to reveal additional genetic alterations besides the translocation. Twenty-six SS from 22 patients were sequenced for 409 cancer-related genes using the Comprehensive Cancer Panel (Life Technologies, USA) on an Ion Torrent platform. The detected variants were verified by Sanger sequencing and compared to matched normal DNAs. Copy number variation was assessed in six tumors using the Oncoscan array (Affymetrix, USA). In total, eight somatic mutations were detected in eight samples. These mutations have not been reported previously in SS. Two of these, in KRAS and CCND1, represent known oncogenic mutations in other malignancies. Additional mutations were detected in RNF213, SEPT9, KDR, CSMD3, MLH1 and ERBB4. DNA alterations occurred more often in adult tumors. A distinctive loss of 6q was found in a metastatic lesion progressing under pazopanib, but not in the responding lesion. Our results emphasize t(X;18) as a single initiating event in SS and as the main oncogenic driver. Our results also show the occurrence of additional genetic events, mutations or chromosomal aberrations, occurring more frequently in SS with an onset in adults.     

Intraoperative real time three-dimensional transesophageal echocardiographic evaluation of right atrial tumor

Right atrial myxomas are uncommon heart tumors that can simulate nonspecific symptoms, such as fever, paroxysmal palpitations, chronic anemia, weight loss, and may escape timely diagnosis until the development of severe complications due to embolism. We present a patient with a history of palpitations. In search for the source of palpitations, a 2D transthoracic echocardiography was performed, showing a right atrial mass. Real time three-dimensional transesophageal echocardiography (RT3DTEE) was performed intraoperative and demonstrated very accurate information about the size and the morphology of the tumor. This is the first case report of a right atrial myxoma visualized intraoperatively by RT3DTEE .     

The open lung concept: pressure controlled ventilation is as effective as high frequency oscillatory ventilation in improving gas exchange and lung mechanics in surfactant-deficient animals

Objective: To demonstrate in experimental animals with respiratory insufficiency that under well-defined conditions, commercially available ventilators allow settings which are as effective as high frequency oscillatory ventilators (HFOV), with respect to the levels of gas exchange, protein infiltration, and lung stability. Design: Prospective, randomized, animal study. Setting: Experimental laboratory of a university. Subjects: 18 adult male Sprague-Dawley rats. Interventions: Lung injury was induced by repeated whole-lung lavage. Thereafter, the animals were assigned to pressure-controlled ventilation (PCV) plus The Open Lung Concept (OLC) or HFOV plus OLC (HFO_OLC). In both groups, an opening maneuver was performed by increasing airway pressures to improve the arterial oxygen tension/fractional inspired oxygen (PaO₂/FIO₂) ratio to L 500 mm Hg; thereafter, airway pressures were reduced to minimal values, which kept PaO₂/FIO₂ L 500 mm Hg. Pressure amplitude was adjusted to keep CO₂ as close as possible in the normal range. Measurements and results: Airway pressure, blood gas tension, and arterial blood pressure were recorded every 30 min. At the end of the 3-h study period, a pressure-volume curve was recorded and bronchoalveolar lavage was performed to determine protein content. After the recruitment maneuver, the resulting mean airway pressure to keep a PaO₂/FIO₂ L 500 mm Hg was 25 ± 1.3 cm H₂O during PCV_OLC and 25 ± 0.5 cm H₂O during HFOV_OLC. Arterial oxygenation in both groups was above L 500 mm Hg and arterial carbon dioxide tension was kept close to the normal range. No differences in mean arterial pressure, lung mechanics and protein influx were found between the two groups. Conclusions: This study shows that in surfactant-deficient animals, PCV, in combination with a recruitment maneuver, opens atelectatic lung areas and keeps them open as effectively as HFOV. Received: 14 October 1998 Final revision received: 11 April 1999 Accepted: 25 June 1999     

A 3-year evolution of linguistic disorders in aphasia after stroke

Aphasia recovery after stroke has been the subject of several studies, but in none the deficits on the various linguistic levels were examined, even though in the diagnosis and treatment of aphasia the emphasis lays more and more on these linguistic level disorders. In this observational prospective follow-up study, we explored whether it is meaningful to investigate the recovery of semantics, phonology, and syntax separately. Fifteen patients with aphasia poststroke were assessed at 3 and 10 days, 7 weeks, 4 and 7 months, and 3 years postonset with the ScreeLing, a linguistic level test, the Aphasia Severity Rating Scale (spontaneous speech) and the Token Test. Group results showed improvement for the overall ScreeLing (P<0.01) and its subparts semantics (P<0.01) and syntax (P<0.01) up to 7 weeks, just as the Token Test (P<0.01). Phonology improved up to 4 months (P<0.05) and spontaneous speech up to 7 months (P<0.05). The recovery pattern of the three linguistic levels did not follow a parallel course, with a great deal of variability in linguistic recovery curves between and within patients. These results suggest that it is meaningful to assess the recovery of the linguistic levels separately, starting from the acute stage poststroke.