Peter Stulz

Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma.

The prognosis of operated patients with non‐small cell lung cancer (NSCLC) is poor despite thorough pre‐operative staging. An improved preselection is needed of patients likely to profit from surgery. This study was undertaken to evaluate the prognostic significance of nuclear p53 overexpression in a cohort of 247 surgically treated patients with NSCLC. It showed that the prevalence of immunohistochemically detectable p53 overexpression varied between different tumour types. p53 overexpression was equally frequent in large cell carcinoma (53 per cent) and in squamous cell carcinoma (54 per cent), but significantly less frequent in adenocarcinoma (34 per cent;P=0·009). p53 overexpression was particularly rare in bronchioloalveolar carcinoma (positivity in 1 of 17 cases). These variations may reflect aetiological differences between the histological subtypes. p53 overexpression was also associated with high tumour grade (P=0·0157) and the presence of lymph node metastasis (P=0·0259), but not with advanced tumour stage. Survival analysis showed no difference in clinical outcome between p53‐positive and p53‐negative tumours within 101 node‐positive tumours. In contrast, survival time was significantly better in p53‐negative tumours than in p53‐positive tumours within the group of 113 node‐negative tumours (P=0·032). Stepwise regression analysis showed that p53 overexpression is an independent prognostic factor in node‐negative NSCLC.

Age does not influence early and late tumor-related outcome for bronchogenic carcinoma

BACKGROUND The influence of age on early and late outcome after surgical resection of bronchogenic carcinoma is unknown. In an attempt to clarify this issue, we reviewed the outcome of 212 consecutive patients with primary lung cancer who had surgical treatment for bronchogenic carcinoma. METHODS Ninety-two patients were younger than 50 years (group 1), and 120 patients were older than 70 years of age (group 2). Squamous cell carcinoma and adenocarcinoma were the most common histologic types in both groups. According to the new international staging classification, a similar proportion of stage I, II, and III were observed in both groups. RESULTS Only the rate of pneumonectomy was significantly higher in younger patients (41% versus 22%, p = 0.002). The overall operative mortality rate in group 1 was 2.2% and 2.6% after pneumonectomy. In group 2 the overall mortality rate was 2.5% and 3.8% after pneumonectomy. Advanced age did not affect operative mortality. The adjusted (tumor-related) survival rate at 5 years was 56% in group 1 and 53% in group 2 (p = 0.93). The adjusted survival rate for patients with stage I was 61% in group 1 and 65% in group 2 (p = 0.21), and for stage IIIa 39% in group 1 and 48% in group 2 (p = 0.43). The adjusted 5-year survival rate was 56% in group 1 and 59% in group 2 for squamous cell carcinoma (p = 0.53) and 49% in group 1 and 42% in group 2 for adenocarcinoma (p = 0.76). CONCLUSIONS Perioperative risk and midterm survival were similar in younger and older patients after surgical resection of bronchogenic carcinoma. We believe that this result is because surgical candidates constitute already a highly selected group of patients. From these data it is not possible to conclude that biologic behavior of lung cancer is more aggressive in younger patients.

Long-term remission after resection, chemotherapy, and irradiation of a metastatic myxoma

Malignant local or metastatic myxomatous tumors of the heart are rare and sometimes present with an unpredictable outcome. The present report demonstrates an unusual case of left atrial myxoma with a rather strange distribution of metastases that had long-term remission after combined surgical resection, chemotherapy, and irradiation of cerebral and pulmonary metastases.

DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma.

Abstract Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity – found in 49.5% of the tumours – was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 ± 10.2) than in p53-negative tumours (10.3 ± 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.

Immediate effects of mitral valve replacement on left ventricular function and its determinants.

Patients undergoing mitral valve surgery are at risk of left ventricular failure in the immediate post-operative period. In order to understand better the mechanisms of post-operative haemodynamic instability, we used transoesophageal echocardiography to assess the immediate response of the left ventricle to mitral valve replacement for mitral regurgitation or stenosis. A decrease in left ventricular preload, despite adequate filling pressures, was common to both groups and suggests the presence of diastolic dysfunction. A marked impairment in global systolic pump function was observed only in the regurgitation group and correlated with the left ventricular afterload. Transoesophageal echocardiography provides valuable information on the individual changes in left ventricular function and its determinants after mitral valve replacement that are not reflected by haemodynamic measurements.

Dyspnea after pneumonectomy: The result of an atrial septal defect

We report the case of severe hypoxemia attributable to right-to-left shunting through an atrial septal defect after right-sided pneumonectomy that developed in a 70-year-old man. Normal right atrial and pulmonary artery pressures were measured. Right-to-left shunting through a patent foramen ovale is known as a rare complication after pneumonectomy. Our patient, however, demonstrated a true atrial septal defect (septum secundum defect) upon open operative repair of the interatrial connection.

Die Trachealruptur : Verzögerte Diagnose durch primär zu tiefe endobronchiale Intubation

ZusammenfassungEin 37-jähriger Mann wurde wegen blutender Mittelgesichtsfrakturen nach einem Motorradunfall an der Unfallstelle vom Notarzt intubiert. Nach Verlegung mit dem Hubschrauber in eine Zentrumsklinik ergab die primäre Diagnostik außer den schweren Mittelgesichtsfrakturen und Weichteilverletzungen keine weiteren pathologischen Befunde. Als der Patient zur Versorgung der Gesichtsschädelfrakturen tracheotomiert wurde, konnte er kaum mehr beatmet und oxygeniert werden. Auch das Legen von Thoraxdrainagen beidseits bei Verdacht auf einen Pneumothorax brachte keine Besserung. Die notfallmäßige Bronchoskopie zeigte einen großen Trachealeinriss in der Pars membranacea unmittelbar oberhalb der Karina. Der Tubus konnte mit Mühe unter bronchoskopischer Kontrolle über die Rupturstelle hinaus in den rechten Hauptbronchus vorgeschoben werden. Primär traten keine Beatmungsprobleme auf, weil der Patient auf der Unfallstelle unbeabsichtigt zu tief intubiert wurde, so dass der Tubus die Rupturstelle oberhalb der Karina abdichtete und das Entstehen eines Mediastinalemphysems mit seinen Folgen verhinderte. Eine beidseitige Beatmung war wegen des Murphyauges des Tubus trotzdem möglich. Erst ein Thoraxröntgenbild zeigte die endobronchiale Lage des Tubus, aus welchem aber keine therapeutischen Konsequenzen gezogen wurden. Die Trachealruptur wurde mit einem gestielten Perikardlappen gedeckt und der Patient ohne Residuen nach Hause entlassen. Dieser Fall zeigt, dass bei einem Trauma im Bereich der Luftwege jede Veränderung der Tubuslage unerwartet schwerwiegende Veränderungen nach sich ziehen kann.AbstractTracheobroncheal rupture is a rare complication of intubation techniques using a stylet. In this case report the patient was intubated by an emergency physician in a preclinical setting after a motorvehicle accident. Iatrogenic tracheal laceration was masked by inappropriate position of the endobronchial tube. By chance ventilation was maintained to both lungs by flow through the Murphys eye of the tube and the lumen of the tube. In correcting the deep tube position after a chest x-ray laceration of the trachea was unmasked and ventilation problems occurred immediately. The tube was replaced under fiberoptical control and the patient was managed for surgical repair using a jet ventilation technique. In this case two complications of endobronchial intubation occurred, but the deep tube placement opposed the effects of the tracheal laceration. This was probably life saving for the patient during emergency transfer by helicopter after the accident. The anaesthesiological management during tracheal repair is discussed.

Left ventricular mass regression following implantation of MIRA bileaflet valves in patients with severe aortic stenosis

The aim of this study was to evaluate the factors that determine the course of left ventricular mass regression in a homogeneous group of patients following aortic valve replacement by use of the mechanical Edwards MIRA bileaflet prosthesis. Furthermore, we examined if the 19-mm valve leads to an equally good outcome when compared with larger 21- and 23-mm valves. We included 79 patients (49 men) with a mean age of 65 ± 9 years operated on for isolated aortic valve replacement with the MIRA valve prosthesis. The analyses included preoperative and postoperative echocardiograms during a follow-up of at least 18 months (995 ± 439 days) after valve surgery. Indication for valve replacement was aortic stenosis in 59 and combined disease (aortic stenosis and regurgitation) in 20 patients. Concomitant coronary artery bypass grafting was performed in 28 patients. Left ventricular mass index declined from 155.6 ± 47 g/m2 to 128.8 ± 35 g/m2 (P < 0.001) at final visit and normalized in 49% of the patients. Female sex and a preoperatively highly elevated left ventricular mass index were identified as risk factors for residual hypertrophy. However, age and valve size did not have a predictive value for completeness of left ventricular mass regression. This study supports the evidence that an extensive preoperative left ventricular hypertrophy results in an incomplete postoperative mass regression in patients with aortic bileaflet valves. It shows that the slightly elevated pressure gradient in MIRA 19-mm valves does not affect left ventricular mass regression.