Orale Zytologie

Zusammenfassung Die orale Zytologie erf?hrt eine Renaissance, die durch die Einführung der Bürste als Entnahmetr?ger und durch die Anwendung zus?tzlicher moderner Verfahren bedingt ist. Die Bürste kann tiefe Schichten der oralen Mukosa erfassen, in denen die squam?se intraepitheliale Neoplasie (SIN) beginnt. Zus?tzliche Verfahren zur Bewertung der biologischen Potenz der gewonnenen oralen Epithelzellen sind: die computerunterstützte Bildanalyse (OralCDx^?), die DNA-Zytometrie, die Immunzytochemie, die Dünnschichtzytologie und molekularbiologische Analysen. Alle genannten Verfahren sind geeignet, die Sensitivit?t (bis zu 100%) und Spezifit?t (bis zu 100%) der oralen Zytologie zu erh?hen. Dennoch gibt es Berichte über orale Plattenepithelkarzinome, die mithilfe der Bürstenbiopsie nicht erkannt wurden. Die Wertigkeit der einzelnen Verfahren kann aktuell aufgrund fehlender vergleichender Studien nicht abschlie?end beurteilt werden. Die Immunzytochemie mit kommerziellen Antik?rpern gegen Laminin 5 ist allseits verfügbar und methodisch einfach. Das nichtinvasive diagnostische Verfahren der methodisch unterstützten oralen Bürstenbiopsie kann einen Beitrag zur frühen Erkennung ausgew?hlter Mundschleimhautl?sionen leisten. Ein positiver Befund oder eine Progression der L?sion bei negativem Befund sind Indikationen zur überweisung des Patienten an Fachkliniken und zur dort durchgeführten Skalpellbiopsie mit histopathologischer Untersuchung. Die histopathologische Begutachtung bleibt der Goldstandard in der definitiven Diagnostik maligner oraler L?sionen.      

Telomere und Telomerase

Zusammenfassung In letzter Zeit fanden spezielle Abschnitte des menschlichen Genoms in der Tumorforschung besondere Beachtung: die Telomere. Telomere, d.h. die Enden aller linearen eukaryotischen Chromosomen, bestehen aus repetitiven DNA-Sequenzen und aus spezifischen Proteinen. Die Funktion der Telomere besteht im Schutz der Chromosomenenden vor Degradation, Fusion und Rekombination. In den meisten somatischen Zellen verkürzen sich die Telomere mit jedem Zellzyklus. Im übertragenen Sinn kann dieser Verlust an telomeren DNA-Sequenzen als eine mitotische Uhr aufgefa?t werden, mit der eine Zelle die Anzahl der Zellteilungen z?hlt und Lebensspanne und Zellalterung dirigiert. Sind die Telomere bis zu einem kritischen Punkt verkürzt, erfolgt die Einleitung des Apoptoseprozesses. Einige wenige Zelltypen entgehen der zellul?ren Seneszenz durch die Expression des Enzyms Telomerase. Dieses Ribonukleoprotein katalysiert die De-Novo-Addition von Nukleotiden an den Telomerenden. Das Enzym ist in den meisten somatischen Zellen in vivo nicht nachweisbar, wurde aber in der Mehrzahl aller Tumorgewebe gefunden. Die Aktivierung der Telomerase scheint Tumorzellen zu unbegrenzter Proliferation und zum Erreichen der Immortalit?t zu bef?higen. Aktuelle Studien zur Telomeraseaktivit?t in Tumoren unterstreichen, da? die Progression eines Tumorzellklons u.a. ma?geblich von der Aktivierung der Telomerase abh?ngt. Deshalb k?nnten Telomeraseinhibitoren neue M?glichkeiten in der Tumortherapie er?ffnen.      

The thrombin inhibitor argatroban does not influence the endothelium-dependent relaxant and contractile responses of isolated rabbit carotid arteries

Atherosclerotic endothelial dysfunctions are associated with a reduced NO production, which is probably due to impaired NO synthase (eNOS) activity or a deficiency of the substrate L-arginine. In the present studies, the influence of argatroban on isolated rabbit carotid arteries was investigated to determine whether the arginine derivative argatroban can improve the endothelium-dependent relaxation.

Rings from rabbit carotid arteries were placed in 10 ml organ baths for isometric tension recording. Endothelial integrity was assessed by the acetylcholine-induced relaxation of PGF₂-precontracted rings; after mechanical removal of the endothelium the relaxation was abolished. Preincubation of the vessels in vitro with L-NAME, an inhibitor of the eNOS, diminished significantly the acetylcholine-induced relaxation by more than 50%. After i.v. application of L-NAME (100 mg/kg) in rabbits, relaxation in response to acetylcholine was significantly reduced compared to the control when the vessels were studied ex vivo in an organ bath. The contractile effects of phenylephrine and 5-HT were slightly enhanced.

Argatroban is a selective, potent, synthetic thrombin inhibitor; after i.v. application at doses of 0.5 and 1.0 mg/kg, a significant prolongation of the plasma coagulation time (measured as thrombin time and a PTT) of up to 60 min was found in rabbits.

In vitro argatroban did not affect the acetylcholine-induced relaxation or the contractile response to phenylephrine and 5-HT. After i.v. application, the ex vivo experiments in the organ bath showed that after 30 min the relaxant responses of the carotid arteries to acetylcholine and the contractile effects of phenylephrine and 5-HT were not influenced by pretreatment with argatroban. The present studies suggest that argatroban has no vascular effects in vitro and ex vivo in normal rabbits.     

Traumatic aneurysms of the descending thoracic aorta

From July 1979 to December 1985 we observed 51 patients with traumatic lesions of the descending thoracic aorta. Twenty-nine had acute ruptures, mostly accompanied by multiple injuries, and 27 had to be operated upon immediately. Twenty-two patients (19 males, 3 females) had chronic traumatic aneurysms of the descending thoracic aorta (more than six weeks after trauma). Mean age at the time of trauma was 24 years. Mean age at time of surgery was 36.5 years. Twelve patients were symptomatic. All were treated surgically. At surgery, complete aortic disruption was found in 15 patients and partial rupture in seven. We did not use aortic shunting of any kind, only aortic cross-clamping. Hypertension was controlled by intravenous drug infusion. The ruptured aortic segment was replaced in all cases by prosthetic Dacron graft. There were no operative deaths. One patient (age 77) died 11 weeks after surgery from multiple organ failure. One case of postoperative paraplegia was observed. This patient recovered almost completely from his neurological deficit.     

Telomerase activity and telomere length in different areas of renal cell carcinoma

Telomerase activity and telomere length were analyzed in a total of 59 surgically removed primary renal cell carcinoma (RCC). The study includes tissue from the centre of the tumor, several different peripheral tumor areas, metastases and secondary tumors. None of the normal renal cortex tissues used as control exhibited telomerase activity. In contrast, telomerase activity was detected in 55 out df 59 (=93%) tested primary RCC. There was no case with intratumoral heterogeneity concerning the telomerase activity status. All metastases and secondary tumors were telomerase-positive. In the four telomerase deficient tumors all measured telomeric repeat fragments were shortened in comparison to the normal tissue. As these patients exhibit no metastases or secondary tumors a less malignant variant of RCC is supposed. There was no correlation between telomerase activity and specific histopathological subtypes of RCC or specific chromosomal aberrations. As telomerase activity is not associated with advanced stages of tumors it may be an important early event in the development of RCC. Thus, telomerase activity may be a prevalent marker for early and late stages of all subtypes of RCC.     

Wavelet analysis of cutaneous blood flow in melanocytic skin lesions

Laser Doppler flowmetry (LDF) is frequently used to study the microcirculation. Usually LDF time series are analyzed by conventional linear methods, mainly Fourier analysis. The aim of this study was to observe dynamic blood perfusion of the skin in malignant and benign melanocytic skin lesions. Wavelet transformation was performed on each LDF time series in order to calculate a vasomotion field. First, the differences in vasomotion between healthy and pigmented skin were evaluated visually on six different time scales of the vasomotion field. In order to quantify the findings, vasomotion scale variance (VSV) was calculated for each scale plane of the vasomotion field. These VSV were compared using contrast DeltaVSV to determine the difference between healthy skin and a pigmented skin lesion in the same patient. After the measurements, the skin lesions were excised and examined histologically. We found that wavelet analysis of LDF time series is a specific, sensitive method for the in vivo identification of malignant melanoma. It is a non-invasive procedure and takes minimal time to be carried out.     

Gender differences in clinicopathological features and survival in surgically treated patients with renal cell carcinoma: an analysis of the multicenter CORONA database

Purpose

To investigate gender differences in clinicopathological features and to analyze the prognostic impact of gender in renal cell carcinoma (RCC) patients undergoing surgery.

Methods

A total of 6,234 patients (eleven centers; Europe and USA) treated by radical or partial nephrectomy were included in this retrospective study (median follow-up 59 months; IQR 30–106). Gender differences in clinicopathological parameters were assessed. Multivariable Cox regression models were applied to determine the influence of parameters on disease-specific survival (DSS) and overall survival (OS).

Results

A total of 3,751 patients of the study group were male patients (60.2 %), who were significantly younger at diagnosis and received more frequently NSS than women. Significantly, more often high-grade tumors and simultaneous metastasis were present in men. Whereas tumor size and pTN stages did not differ between genders, clear-cell and chromophobe RCC was diagnosed less frequently, but papillary RCC more often in men. Gender also independently influenced DSS (HR 0.75, p < 0.001) and OS (HR 0.80, p < 0.001) with a benefit for women. However, inclusion of gender in multivariable models did not significantly gain predictive accuracies (PA) for DSS (0.868–0.870, p = 0.628) and OS (0.775–0.777, p = 0.522). Furthermore, no significantly different DSS and OS rates were found in patients undergoing NSS.

Conclusions

This study demonstrates important gender differences in clinicopathological features and outcome of RCC patients with improved DSS and OS for women compared to men, even if solely patients with clear-cell RCC or M0-stage are taken into evaluation. However, inclusion of gender in multivariable models does not significantly gain PA of multivariable models.