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Abstract: In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy.Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens.Therapy-induced tumor regression was classified according to a three-step tumor regression grading system.In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% (n=11) pretherapeutic lymph node status was maintained.Of 26 patients with posttherapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III).Patients with posttherapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02).Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.

Abstract. Purpose: About 40% of non-small cell lung cancer (NSCLC) patients are candidates for systemic chemotherapy, despite the fact that at diagnosis most NSCLC are usually chemoresistant both in vivo and ex vivo. It is important to develop sufficient methods of prediction of the response to chemotherapy and to find molecular markers that may prognose this response. Therefore, a study on the relationship of p53 gene status to the ex vivo chemosensitivity of primary human NSCLC was performed. Methods: Three drug combinations (carboplatin/etoposide, cyclophosphamide/etoposide/epirubicin, and paclitaxel/carboplatin) were tested in a modified ATP cell viability assay. A group of 28 cases of primary human NSCLC was assessed. Results: Ex vivo chemosensitivity testing showed that tumors with p53 mutations were significantly more resistant to the cyclophosphamide/etoposide/epirubicin regimen than with normal p53 gene (P = 0.012). However, no correlation was observed for two other treatment regimens. Conclusion: Mutations in the p53 gene can lead to enhanced chemoresistance, confirming the hypothesis that the p53 gene may serve as a marker of tumor response to treatment in NSCLC. However, the data also illustrate that some additional factors might contribute to drug resistance of the examined tumors.

Zusammenfassung: Innerhalb von 15 Monaten führten wir an unserer Klinik 207 Mediastinoskopien durch; bei 147 Patienten lag ein Bronchialkarzinom vor. Neben der Tumorhistologie und der Lokalisation des Primärtumors wurde insbesondere das detaillierte Befallsmuster der mediastinalen Lymphknoten und das Probengewicht (mit Berechnung einer Normalverteilung) der entnommenen Lymphknotenbiopsien ermitttelt.    Es konnten nicht immer alle mediastinoskopisch erreichbaren LK-Stationen (paratracheal und tracheobronchial beidseits, infracarinal) biopsiert werden. Besonders häufig gelang die Biopsie tracheobronchial rechts (94%), infracarinal (92%) und tracheobronchial links (82%). Das Durchschnittsgewicht der entnommenen Proben lag je nach Station zwischen 0,39 g (paratracheal links) und 1,12 g (infracarinal). Bezogen auf die unterschiedliche Entnahmehäufigkeit ergab sich für alle Stationen (mit Ausnahme des allerdings selten nachweisbaren prätrachealen Lymphknotens) eine ähnliche Befallshäufigkeit (19–27%). Bei 49% der Patienten lag kein mediastinaler LK-Befall vor, 1 LK-Station war in 20% befallen, mehr als eine Station in 31%. Je nach Lokalisation des Primärtumors ergaben sich unterschiedliche Häufigkeiten einer mediastinalen Metastasierung: Insbesondere die zentralen Tumoren wiesen häufiger mediastinale LK-Metastasen auf als die peripheren. Die Lokalisation in den verschiedenen Lungenlappen war ebenfalls von Bedeutung. Den deutlichsten Einfluss auf die Häufigkeit einer ipsi- bzw. kontralateralen Metastasierung hatte die Histologie des Primärtumors: Ein Befall von mindestens 1 LK-Station fand sich bei 61,4% der Adenokarzinome; hingegen nur bei 41,1% der Plattenepithelkarzinome. Der kontralaterale Befall (N3) wurde bei 16,1% (Plattenepithelkarzinome) bzw. 29,5% (Adenokarzinome) gesichert. Nodal negativ waren 57,1% (Plattenepithelkarzinome) bzw. 41% (Adenokarzinome); ipsilateral positiv (N2) erwiesen sich entsprechend 26,8% und 41%.    Die hohe diagnostische Aussagekraft der Untersuchung mit einem prozentualen Lymphknotenbefall von 19–27% je nach LK-Station reflektiert einerseits die weite Indikationsstellung zu diesem Eingriff, weist aber auch darauf hin, dass eine repräsentative Gewebsentnahme erforderlich ist. Dabei können Normalverteilungs-Kurven der Probengewichte eine Standardisierung i.S. einer Qualitätskontrolle erleichtern.

Summary To study the influence of non-coronary collateral blood circulation (NCCBC) on the integrity of the ischemic myocardium a right-sided thoracotomy was performed on 15 anesthetized dogs. Following a total cardiopulmonary bypass (CPB), ventricular fibrillation was induced, during which 2,000 ml calcium-free cardioplegic solution LK 352 was given at the aortic root over an 8–10-min period. Precautions were taken to prevent retrograde blood flow into the coronary system via the coronary sinus. After 90 min of ischemia, ten of the dog hearts were reperfused with systemic blood for the next 30 min. Transmural biopsies were taken from the apex of the left ventricle at the following intervals: (1) before CPB, (2) immediately after the infusion of LK 352, (3) following 90 min of ischemia, (4) after 5 min, (5) after 15 min, and finally (6) after 30 min of reperfusion and were then studied ultrastructurally. The presence of NCCBC was documented by the observation of erythrocyte-filled blood vessels in the biopsies corresponding to nos. 2 and 3 of the above.

Abstract In the scope of a prospective multi-centre study after neoadjuvant combined chemotherapy (carboplatin, ifosfamide, etoposide, vindesine) and radiotherapy (45 Gy) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression. Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion. The mean age of the patients was 57 years. The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers. Marked scarry fibrosis in the region of the former primary tumour, concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression, whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue. Using a three-step regression system, 3 tumours could be classified as grade I (no or only slight tumour regression), 10 tumours as grade IIA (marked but incomplete tumour regression, more than 10% vital tumour tissue), 20 tumours as grade IIB (less than 10% vital tumour tissue) and 7 tumours as grade III (complete tumour regression without vital tumour tissue). After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression ("responders") the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression ("non-responders") with a median survival period of 13.7 months (log-rank test, P=0.020). The resection specimens analysed, which were obtained 7 weeks (on average) after the end of radiochemotherapy, did not show specific changes due to preoperative therapy, but quite characteristic histological alterations in the former tumour area were registered, which had been induced by combined neoadjuvant radiation and chemotherapy. The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer.

Ehrlich-Ascitestumorzellen wurden mit dem Urin bzw. der Galle von Kaninchen, die 50–100 mg Endoxan pro kg Körpergewicht erhalten hatten, inkubiert. Diejenigen Konzentrationen, die zu einer starken Hemmung der DNS-Synthese (Einbau von H3-Thymidin) und zu einer deutlichen Herabsetzung der RNS-Synthese (Einbau von H3-Cytidin) führten, hemmen weder die Milchsäurebildung der Tumorzellen noch setzen sie deren DPN-Gehalt herab. Zur Aufhebung der Transplantierbarkeit der Tumorzellen genügen Dosen, welche die DNS-Synthese auf etwa 70% herabsetzen.

Summary Using the GIA auto suture instrument, a “continuous gastromy” was performed on 12 patients with nonresectable carcinomas of esophagus or pharynx and with stenosis or fistula of esophagus after cobalt radiation. The advantages of this gastrostomy, performed as a standard procedure based on the idea of Depage, Janeway, and Spivak, over the usual gastrostomy of Witzel or Kader, are: 1. It is unneceBary to open the stomach during the abdominal operation; 2. there is no leakage of gastric juice on the skin surface and no danger of rapid obliteration by adhesion of the serosal surface. The tube need only be inserted for feedings.