Adult primary pulmonary primitive neuroectodermal tumor: molecular features and translational opportunities.

Primitive neuroectodermal tumors (PNET) arising directly from the lung are very rare but particularly aggressive neoplasms. We report a case of a 31-y-old man with primary pulmonary neuroectodermal tumor. We review the clinical as well as pathological features. As typical for these tumors, the diagnosis was initially delayed in our patient and prognosis was poor despite aggressive surgical resection, postoperative chemotherapy and local irradiation. Recent biological insights have revealed unique chromosomal translocations crucial to the pathogenesis of these tumors, most notably the EWS-FLI-1 translocation. We provide an overview of the molecular features of the Ewing Sarcoma Family of Tumors (ESFT) including PNET and their potential implications for therapeutic targeting.

One thousand repeat sternotomies for congenital cardiac surgery: risk factors for reentry injury.

BACKGROUND: Reentry injury is a risk associated with repeat sternotomy for cardiac surgery. This risk has been well defined for adults, but there is less information available for patients with congenital heart disease. The goal of this review was to identify the incidence, risk factors, and outcomes for reentry injury in patients with congenital heart disease. METHODS: Eight hundred two patients with congenital heart disease had 1,000 consecutive repeat sternotomies between August 2000 and November 2007. Records were reviewed for demographics, history, operative techniques, and outcomes. Univariate risk factors for reentry injury and operative mortality were assessed. RESULTS: Median age and weight were 2.1 years (range, 0.1 to 34.6 years) and 11 kg (range, 2.5 to 123 kg). There were 639 second, 287 third, and 74 fourth or higher sternotomies. There were 13 reentry injuries (1.3%) involving right ventricle-pulmonary artery conduits (n = 4), aorta or aortic conduits (n = 3), right ventricular outflow tract patches or pseudoaneurysms (n = 3), and others (n = 3). Risk factors for injury were presence of a right ventricle-pulmonary artery conduit (6 of 115 with conduit [5.2%] versus 7 of 885 without [0.8%]; p < 0.001) and sternotomy number (relative risk, 2.28; p < 0.001). Reentry injury was associated with longer procedure times (median, 420 minutes with injury versus 248 without; p < 0.001). Operative mortality occurred in 18 patients and was associated with sternotomy number and procedure time (p < 0.001), but not reentry injury (p = 0.2). CONCLUSIONS: Risk of reentry injury during repeat sternotomy for congenital heart disease is low. Increasing sternotomy number and the presence of a right ventricle-pulmonary artery conduit are risk factors for reentry injury. However, reentry injury is not associated with increased risk of operative mortality.

Perioperative risks and outcomes of atrioventricular valve surgery in conjunction with Fontan procedure.

BACKGROUND: Long-term outcomes of staged single-ventricle palliation can be impaired by atrioventricular valve (AVV) regurgitation. Atrioventricular valve repair or replacement has been shown to improve late outcomes, but little data exist regarding the associated perioperative morbidity. This study aimed to evaluate the additional perioperative risks associated with single-ventricle AVV surgery. METHODS: Two hundred thirty-six consecutive Fontan procedures were retrospectively reviewed. Group 1 (n = 21, with concomitant AVV repair [n = 19] or replacement [n = 2]) was compared with group 2 (n = 215, no AVV surgery) with regard to preoperative characteristics and perioperative outcomes. Atrioventricular valve regurgitation was graded as 1 (none or trivial) to 4 (severe). RESULTS: Group 1 patients were older (4.3 +/- 3.7 versus 3.0 +/- 2.6 years; p = 0.04) and had longer cardiopulmonary bypass (118 +/- 38 versus 85 +/- 28 minutes; p < 0.001) and aortic cross-clamp times (33 +/- 32 versus 14 +/- 21 minutes; p < 0.001). There were no differences between groups regarding diagnosis, weight, hospital or intensive care unit length of stay, ventilator time, or 12-hour chest tube output. Postoperative complications were similar between groups, including bleeding (0 of 21 versus 8 of 215; p = 0.8), neurologic injury (1 of 21 versus 9 of 215; p = 0.7), arrhythmias (1 of 21 versus 24 of 215; p = 0.6), and operative mortality (0 of 21 versus 1 of 215; p = 0.1). Group 1 AVV regurgitation significantly decreased after surgery (3.0 +/- 0.9 preoperatively versus 1.7 +/- 0.9 postoperatively; p < 0.001). CONCLUSIONS: Atrioventricular valve surgery has been shown to improve late outcomes for single-ventricle patients. This study demonstrates that AVV surgery performed with the Fontan procedure increased operative times, but did not significantly increase perioperative morbidity or mortality. This information supports appropriate utilization of AVV surgery for single-ventricle patients.

Ubiquitin binds to and regulates a subset of SH3 domains.

SH3 domains are modules of 50-70 amino acids that promote interactions among proteins, often participating in the assembly of large dynamic complexes. These domains bind to peptide ligands, which usually contain a core Pro-X-X-Pro (PXXP) sequence. Here we identify a class of SH3 domains that bind to ubiquitin. The yeast endocytic protein Sla1, as well as the mammalian proteins CIN85 and amphiphysin, carry ubiquitin-binding SH3 domains. Ubiquitin and peptide ligands bind to the same hydrophobic groove on the SH3 domain surface, and ubiquitin and a PXXP-containing protein fragment compete for binding to SH3 domains. We conclude that a subset of SH3 domains constitutes a distinct type of ubiquitin-binding domain and that ubiquitin binding can negatively regulate interaction of SH3 domains with canonical proline-rich ligands.