Franz Eckersberger

Long-Term Results After Repeated Surgical Removal of Pulmonary Metastases

BACKGROUND Although surgical resection is accepted widely as first-line therapy for pulmonary metastases, few data exist on the surgical treatment of recurrent pulmonary metastatic disease. In a retrospective study, we analyzed patients who were operated on repeatedly for recurrent metastatic disease of the lung with curative intent over a 20-year period. METHODS From 1973 to 1993, 396 metastasectomies were performed in 330 patients. The study population included patients with any histologic tumor type who had undergone at least two (range, 2 to 4) complete surgical procedures because of recurrent metastatic disease. Surgical and functional resectability of the recurrent lung metastases and control of the primary lesion served as objective criteria for reoperation. A subgroup of 35 patients that included patients with histologic findings such as epithelial cancer and osteosarcoma then was analyzed retrospectively to calculate prognosis and define selection criteria for repeated pulmonary metastasectomy. RESULTS The 5- and 10-year survival rates after the first metastasectomy were 48% and 28%, respectively. The overall median survival was 60 months. A mean disease-free interval (calculated for all intervals, with a minimum of two) of greater than 1 year was significantly associated with a survival advantage beyond the last operation. Univariate analysis failed to show size, number, increase or decrease in number or size, or distribution of metastases as factors related significantly to survival. CONCLUSIONS Although patients with different histologic tumor types were included, the study population appeared to be homogeneous in terms of survival benefit and prognostic factors, and it probably represented the selection of biologically favorable tumors in which histology, size, number, and laterality are of minor importance. We conclude that patients who are persistently free of disease at the primary location but who have recurrent, resectable metastatic disease of the lung are likely to benefit from operation a second, third, or even fourth time.

Evidence for a role of FGF-2 and FGF receptors in the proliferation of non-small cell lung cancer cells

Basic fibroblast growth factor (FGF‐2) has been implicated in the progression of human tumours via both autocrine and paracrine (angiogenic) activities. We investigated the expression of FGF‐2 and FGF receptors (FGFR‐1 to ‐4) in NSCLC cell lines (N = 16), NSCLC surgical specimens (N = 21) and 2 control cell lines. Our data show that almost all NSCLC cells produce elevated levels of FGF‐2 and FGFR in vitro and in vivo. FGF‐2 expression did correlate with a short doubling time as well as with potent anchorage‐independent growth of NSCLC cell lines. In contrast with control cells, NSCLC cells did not secrete considerable amounts of FGF‐2 into the extracellular space. Expression levels of FGFR‐1 and ‐2 in NSCLC cell lines correlated with FGF‐2 production. FGFR were located at the plasma membranes in some low FGF‐2‐producing NSCLC and control cell lines. These cells were sensitive to the proliferative effect of recombinant FGF‐2 (rFGF‐2). In NSCLC cell lines with an enhanced FGF‐2 production, representing the majority studied, FGFR localisation was predominantly intracellular. These cells were insensitive to both the proliferative effect of rFGF‐2 and growth inhibition by FGF‐2‐neutralising antibodies. In contrast, several agents antagonised FGF‐2 intracellularly impaired growth of almost all NSCLC cell lines. Our data suggest a role of FGF‐2 and FGFR in the growth stimulation of NSCLC cells possibly via an intracrine mechanism. Int. J. Cancer 83:415–423, 1999.

The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.

BACKGROUND The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment. METHODS Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11). RESULTS A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027). CONCLUSIONS In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.

Fibrin Sealing in Surgical and Nonsurgical Fields

We first treated a patient with fibrin sealant in an orthopedic procedure 18 years ago. This was a case of fistulous osteomyelitis following total hip replacement. We packed the bone cavity with homologous spongiosa and fibrin sealant, a technique which has proved successful. In numerous animal experiments and laboratory studies it has been demonstrated that the use of homologous fibrin sealant clearly conduces to the incorporation of bone grafts. This advantage is of particular significance when filling major defects, when no autologous bone is available for grafting, and when combating infections. The fibrin sealant system improves vascularization and this in turn enhances osseous remodeling of bone grafts. The adhesive strength of fibrin sealant is sufficient for refixation of osteochondral fragments. For its hemostatic effect, fibrin sealant is applied to seal major cancellous bone defects or to stanch oozing hemorrhages in patients with bleeding disorders. In cases of ruptured Achilles tendon with extensive necrotic areas, fibrin sealant improves the formation of granulation tissue on the surface of the defect. In general, vascularization and healing are significantly reduced when heterologous fibrin sealants are used.

Molecular genetic differentiation between primary lung cancers and lung metastases of other tumors

When solitary pulmonary tumors are observed in patients with a history of cancer, differentiation between metastasis and primary lung cancer is crucial for appropriate therapy. Assuming that p53 mutations are conserved in metastases, mutation analysis of the p53 gene would be a valuable tool in differentiating metastases from primary carcinomas of the lung. In nine of 267 resected lung tumors, the origin of the lung tumor could not be defined histologically. Five patients had a history of colorectal carcinoma, one had a history of breast carcinoma, one had a history of soft-tissue carcinoma, and one had a history of head and neck carcinoma. One patient with a clear cell carcinoma of the lung had been surgically treated for both renal and thyroid cancer. Material from one patient with adenocarcinoma of the lung, histologically defined regional lymph nodes, and distant brain metastasis served as a control. We extracted deoxyribonucleic acid from the snap-frozen tissue of the unclassified lung tumors, from paraffin-embedded tissue of the previously removed primary cancers, and also from peripheral blood of the patients. Exons 2 to 11 of the p53 gene were amplified in separated polymerase chain reactions and directly sequenced. In all cases, the presence of germline mutations was excluded by analysis of peripheral blood deoxyribonucleic acid. The p53 mutation detected in the deoxyribonucleic acid of the lung tumor of the control patient proved to be conserved in the lymph nodes as well as in the brain metastasis. In two cases, the lung tumors exhibited a p53 mutation not present in the previously removed primary tumor and were therefore classified as new primary lung cancers. In five cases, the lung tumors proved to be metastases of the first tumor, exhibiting the identical p53 mutation. One of these lung tumor samples could be identified as a metastasis from the renal cancer, but the corresponding thyroid cancer material was different. For two cases, molecular analysis remained inconclusive. In one case, no p53 mutation could be found in the compared samples; in the other, no deoxyribonucleic acid could be extracted. Analysis of p53 mutations allowed exact classification in tumors for which standard methods failed to distinguish between metastasis or primary tumor. More than two thirds of lung tumors in patients with previous gastrointestinal carcinoma were revealed to be metastases, but second primary lung cancer could also be diagnosed. This diagnosis allowed correct surgical and adjuvant treatment of these patients.

Survival after surgical treatment of recurrent pulmonary metastases

OBJECTIVE Resection of lung metastases is a generally accepted therapeutic strategy today. This retrospective study was performed in order to estimate the value of an aggressive surgical approach in recurrent metastatic disease of the lung. METHODS The survival rates of 42 patients undergoing repeated resectional treatment for recurrent lung metastases (group A) were compared to the outcome of a total of 288 patients after a single surgical intervention for lung metastases (group B). Survival rates and the relative effects of the various prognostic factors were calculated according to Kaplan-Maier and Mantel Cox or Wilcoxon test. Histology of the primary tumors in group A consisted of 18 carcinomas, 22 sarcomas and two melanomas, in group B the distribution was 64% carcinoma, 27% sarcoma and 9% melanoma. The mean follow-up period was 88.5 months for group A and 27 months for group B. RESULTS The overall survival rate for group A was 48% at 5 years and 30% at 10 years, the survival rate for group B was 34% at 5 years. CONCLUSION Long-term survival rates superior to those after single resectional treatment for lung metastases encourage an aggressive surgical approach for this disease.

Carcinogen-specific mutations in the p53 tumor suppressor gene in lung cancer

Mutations of the p53 tumor suppressor gene, whose encoded protein is one of the chief regulators of the cell cycle, are proving to be the most common genetic alteration in human cancer. Point mutations have been detected in numerous human solid tumors. The types of point mutations in the p53 gene vary considerably in different kinds of human cancers, suggesting that specific etiologic agents are responsible for typical kinds and sites of mutations in the p53 gene. This study reports the detection of two unusual p53 mutations in a series of patients with lung cancer. The first case showed a one-base pair deletion at the end of exon 8, which is rarely affected by mutations, leading to a frameshift involving the following intron 8, exon 9, and intron 9. The second case exhibited two point mutations in codon 273, both either localized in the same codon on one allele or each mutation localized on a different allele in codon 273. Interestingly, the two mutations can be attributed to different mechanisms of base substitution. This is the first report of this kind. Because of evidence that the nature and site of p53 mutations reflect not only the mutagens involved in tumorigenesis but also the capacity for malignant transformation, the characterization of mutations of the p53 gene may provide a basis for assessing further risk factors, as well as for estimating prognosis in patients with lung cancer.

Endoluminale Schienung (Stenting) bei Stenosen des Tracheobronchialsystems

ZusammenfassungDie endoluminale Schienung mittels Silikonstents ermöglicht es, bei stenotischen Prozessen des tracheobronchialen Systems, eine rasche Wiederherstellung der Atemwege zu erreichen. Damit kann entweder Zeit für eine spätere operative Sanierung gewonnen oder, im Falle von operativ nicht lösbaren Situationen, eine palliative Lösung erreicht werden. Stents sind für alle anatomischen Bereiche, von unmittelbar subglottisch bis in die Lappenbronchien hin, einsetzbar. Der wesentliche Vorteil liegt in der Vermeidung eines Tracheostomas und der guten Gewebsverträglichkeit, die auch eine langfristige Anwendung erlaubt. Berichtet wird über die technischen Aspekte des tracheobronchialen Stentings und die damit erzieiten Resultate bei 38 Patienten.SummaryEndoluminal insertion of siliconstents into the tracheobronchial system enables immediate restoration of stenotic airways. The device can be used temporarily until later operative treatment or it can be used as a definitive solution for otherwise irreparable situations. Stents are available for all anatomical regions from the subglottic area down to the lobar bronchi. The main advantage is the avoidance of a tracheostoma together with the good tolerance of the silicon material by the bronchial mucosa, allowing long term application. We report about the technical aspects of stent insertion and our experience and results in 38 patients.

Thorakoskopische Ösophagektomie: Technik, erste Erfahrung und kritische Bewertung

ZusammenfassungGrundlagen: Die radikale Ösophagektomie erfordert den Zugang durch Thorakotomie, der transhiatale Weg ermöglicht aufgrund fehlender Sicht keine onkologisch adäquate Operation. Als minimal invasives Verfahren sollte die Thorakoskopie eine Ösophaguspräparation und -extraktion unter videoendoskopischer Kontrolle bei gleichzeitiger Vermeidung der Thorakotomie gewährleisten.Methodik: Über 4 Trokare (10 und 12 mm im 4. und 7. ICR) wird unter videothorakoskopischer Sicht die mediastinale Pleura inzidiert, die V. azygos mit dem Endo-GIA ligiert und durchtrennt und der Ösophagus von der Trachealhinterwand, dem rechten Hauptbronchus, der Aorta und dem Perikard abpräpariert. Im Vergleich zur „blunt dissection” kann dabei der Muskelmantel der Speiseröhre mit Sicherheit erhalten sowie periösophageales Lymph-Bindegewebe und adhärente paraösophageale Lymphknoten mitreseziert werden. Die Extraktion des Präparates nach zervikal sowie die Inspektion des ösophagusbetts erfolgen ebenfalls unter videothorakoskopischer Sicht.Ergebnisse: Bisher wurden 3 Patienten auf diese Weise operiert. Methodisch bezogene Komplikationen traten dabei nicht auf, allerdings erfolgte die Entwöhnung vom Respirator bei allen Patienten nur schrittweise, 1 Patient verstarb 2 Monate nach der Operation an einer nekrotisierenden Pankreatitis.Schlußfolgerungen: Die thorakoskopische Ösophagektomie ist technisch durchführbar und ermöglicht die Präparation und Extraktion des Ösophagus unter Sicht ohne Thorakotomie. Im Vergleich zur „blunt dissection“ stellt sie — vor allem bei Karzinomen im oberen Drittel — eine sichere und onkologisch verbesserte Methode dar, die Radikalität einer transthorakalen Ösophagektomie ist derzeit allerdings nicht erreichbar. Der Vorteil der verkürzten Rekonvaleszenz in der minimal invasiven Chirurgie kann bei unserer bisherigen Erfahrung noch nicht nachvollzogen werden.SummaryBackground: Thoracotomy is the approach for radical treatment of esophageal cancer, transhiatal “blunt dissection” is an oncologically insufficient but less invasive procedure. With the thoracoscopic technique, we tried to combine both: a minimal invasive procedure and an adequate and safe preparation of the thoracic esophagus under visual control.Methods: With the use of 4 open valved trocars (10 and 12 mm in the 4th and 7th intercostal space), the videothoracoscopic procedure includes the incision of the mediastinal pleura, the ligation of azygos vein by the Endo-GIA, the exact dissection of the esophagus from the tracheal wall, the right main bronchus, the aorta and the pericardium. This technique protects the esophageal wall from injuries when compared with “blunt dissection” and includes the removal of periesophageal tissue and lymphnodes. The cervical extraction of the mobilized specimen and the residual esophageal bed can be controlled by video monitoring.Results: 3 male patients underwent thoracoscopic esophagectomy without complications in respect of the endoscopic method, but they all had a prolonged stay in the intensive care unit. 1 patient died 2 months after surgery from a necrotizing pancreatitis.Conclusions: Thoracoscopic esophagectomy is a procedure which enables the dissection of the esophagus under visual control without thoracotomy. It provides a safer and oncologically more adequate operation when compared to “blunt dissection”, however its radicality can not compete with the open thoracic procedure. The technique appears beneficial mainly for esophageal cancer in the upper thoracic level when thoracotomy should be avoided.

Changes in activities performed in leisure time after open heart surgery

To assess any changes made in the leisure activities performed after open heart surgery, 94 patients (48 with aortocoronary bypass operation, 46 with valve replacements) were asked exactly one year postoperatively whether activities, collected in a list of 21 items, had increased, decreased or remained equal since their operation. In spite of the fact that most leisure activities seemed to have remained unchanged, after operation patients seem to undertake activities quite contrary to their motivations for undergoing surgery in the first place: active participation (such as involvement in some kind of sport, going out to cinema, theatre, restaurants,...) decreases, whereas passive activities (such as watching sports on television, listening to music,...) increases significantly. Although 90% of the patients stated their physical, and 67% their emotional status, as being clearly improved compared to preoperative values, the experience of body limitations as well as of fear and anxiety seems to be so durable that the patients, now in good condition, become passive onlookers and cease to participate in social life.