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Biomedical subjects

F Klinke

Publications and source records attributed to F Klinke.

At least 19 recordsLinked to original sources

Trimodality therapy in stage III non-small cell lung cancer: prediction of recurrence by assessment of p185neu.

In a trimodality treatment approach for stage III non-small cell lung cancer the prognostic impact of pretherapeutic p185neu assessment was evaluated. Fifty-four patients were admitted to chemotherapy followed by twice-daily radiation with concomittant low-dose chemotherapy and subsequent surgery. Immunohistochemical assessment of p185neu expression was performed in paraffin-embedded mediastinal lymph node metastases, by mediastinoscopy biopsy prior to therapy. Paraffin-embedded biopsies of mediastinal lymph node metastases were available in 33 cases. Seven out of eight patients with positive p185neu staining developed distant metastases, in contrast to seven out of 25 negative cases. Expression of p185neu in mediastinal lymph node metastases was a significant predictor for progression-free survival (p=0.047) and resulted mainly from significant differences in metastases-free survival (p185neu-positive versus p185neu-negative: median, 11 versus 19 months; 2- and 3-yr rates, 13% and 0% versus 40% and 32%; p=0.04). On the basis of these preliminary results it was concluded that further evaluation of p185neu expression in trials on neoadjuvant and adjuvant therapy is warranted. When the prognostic impact of p185neu in such trials with larger patient numbers is confirmed, this may contribute to the identification of stratification variables for future treatment approaches of non-small cell lung cancer.

Adult

Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment.

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.

Adenocarcinoma

[Neoadjuvant radiochemotherapy in locally advanced non-small cell bronchial carcinoma. Initial results of a prospective multicenter study].

PURPOSE: In the last years new encouraging methods in the therapy of bronchial carcinoma have been elaborated. The early stages of bronchial carcinoma are still a domain of operative treatment. The long-term results of surgical treatment for locally advanced disease are considered to be unfavourable. Multimodal treatment concepts with simultaneous or consecutive application of radio-chemotherapy followed by surgical resection seem to reveal improved possibilities of therapy. PATIENTS AND METHODS: General treatment consists of 2 blocks of neoadjuvant chemotherapy with carboplatin, ifosfamide and etoposide, followed by a third course, consisting of carboplatin and vindesine. Simultaneously with the third course a hyperfractionated, accelerated radiotherapy with a single dose of 1.5 Gy 10 times per week is applied. The total dose is 45 Gy in 3 weeks, given at least to the 80% isodose. After restaging, tumor resection is carried out. Patients without tumor are randomized for prophylactic brain irradiation. RESULTS: From January 1992 up to 1.10.1993 25 patients have been treated in accordance to the study. All tumors were locally advanced (stage IIIa and IIIb). Until 1.10.1993 4 patients died, 2 of them certainly related to the tumor. Thirteen patients have been resected after neoadjuvant treatment. In 11 of these cases a R0-, and in 2 cases a R1 resection has been carried out. Tumor cells have been found only in 5 histologies. The hematotoxic side effects under competing RTX/CTX seemed to be unproblematical (RTOG/grade II). Problems occurred with 4 cases of serious esophagitis (RTOG/grade III to IV) and 2 cases of pneumonitis with 1 case ending lethally. CONCLUSION: Preliminary results of our study show the feasibility of multimodal treatment. A favourable 1-year survival rate after aggressive multimodal therapy and a high resection rate in previously unresectable patients could be demonstrated.

Adenocarcinoma

[Multifocal bronchial cancer].

Since the entire surface of the bronchial mucosa is exposed to carcinogenic stimuli, the possibility of developing multiple primary lung carcinomas must be discussed. Multiple primary lung carcinomas do not necessarily occur simultaneously (synchronous), they can also develop successively (metachronous). They can be localized ipsilateral as well as contralateral, and histologically they have an identical or different character. In our study of 612 patients with bronchogenic carcinoma we found 18 patients (2.9%) to have a synchronous multiple primary carcinoma. The growing clinical relevance of the diagnosis of the multiple primary bronchogenic carcinoma--which is certainly diagnosed to rarely--and the distinction from metastases will be discussed.

Adult

[The tumorlet carcinoid in bronchiectasis-changed lungs. An example of a multifocal, endocrine tumor].

Tumorlets of the lungs are multifocal hyperplasias of endocrine cells which may develop via nodular hyperplasia into peripheral, occasionally also metastatic, carcinoids. They are observed with a particular frequency in bronchiectasis. Resected material obtained from patients with bronchiectasis (4 women, 3 men, mean age 43.5 years, range 19-66 years) were submitted to conventional histological studies employing HE, PAS and van Gieson staining, and also to an immunohistological analysis. Conventional staining sufficed to identify endocrine cell proliferations in the scarred lung tissue in 3 preparations. An assignment to bronchioles and alveoli with conventional histology was, in view of the extensive scarring of the lung parenchyma, very difficult, but was accomplished with the aid of immunohistological investigation. As a multifocal tumour, the tumourlet suggests itself as a model, employing immunohistochemistry, for studying the formal genesis of neuroendocrine tumours of the lung, since it shows the earliest intra-epithelial neoplastic transformations through in situ tumour to carcinoid.

Adult

Thymus carcinoid.

A carcinoid of the thymus was studied by light- and electron-microscopy, immunohistology and flow-cytometry. The tumor showed a ribbon- and festoon-like growth-pattern with foci of necrosis, invasion of vessels and infiltration of mediastinal lymph nodes. The cytoplasma of the tumor-cells contained neuroendocrine granula and immunohistochemistry of ACTH was positive. The tumor-cells were connected by desmosomes, correlating to a pre-keratin positive immunohistology. In flow-cytometry the tumor-cells showed a near haploid DNA aneuploidy which is an extremely rare finding in solid tumors and in the few cases described indicative for treatment resistance.

Carcinoid Tumor

Morphological hazards of deuterium oxide as a cardioplegic agent.

To determine the cardio-protective effect of heavy water on the ischemic myocardium, a thoracotomy was performed on 18 mongrel dogs. The animals were connected to the extracorporeal circulation in a standardized experimental procedure. Following total cardiopulmonary bypass, 2,000 ml of a standard cardioplegic solution (LK 352) was infused at the aortic root of 10 dogs, which served as controls (group I), and the same solution containing 20% of 99.8% deuterium oxide was given at the aortic root of the remaining animals (group II). At the end of 60 minutes of ischemia, 1,000 ml of the solutions was again administered at the aortic root of the corresponding animals. Myocardial biopsies were taken from the apex of the left ventricle of each dog before cardiopulmonary bypass, immediately after the infusion of the cardioplegic solutions, following 90 minutes of ischemia, and after 30 minutes of reperfusion, and studied ultrastructurally. Whereas the ultrastructure of the myocardium of group I was well preserved at the end of the ischemic period, deuterium-oxide-treated hearts showed extensive focal and global myofilamentolysis and lysis of whole myocytes. Structural damage to glycogen, nuclear chromatin dispersal, severe intracellular edema and complete rupture of the intercalated discs were characteristic findings. At the end of ischemia, all the hearts of group I could be resuscitated. During the ischemia, all the hearts of group II developed into stone hearts. Biochemical studies on a second series showed a higher ATP depletion and a significantly higher lactate accumulation in group II than in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The influence of non-coronary collateral blood supply on the electively arrested heart during ischemia and reperfusion.

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. To assess the degree of ischemic injury and the extent of myocardial recovery during reperfusion, a scoring system based on a semiquantitative assessment of the characteristic morphological changes was used. The average result of the separately assessed subendo- and subepicardial layers represented the score, which was plotted on the ischemic injury and the recovery scale, thus making a direct comparison of the hearts possible. All the hearts generously supplied with blood via extracoronary routes during ischemia showed minimal and reversible ischemic injuries. They recovered more quickly and more completely following reperfusion than those hearts without NCCBC. From these results we conclude that despite its warming-up effect on the myocardium and its tendency to wash out the cardioplegic solution, the NCCBC generally protects the myocardium from serious ischemic injuries and shortens the period of recuperation during the reperfusion.

Animals

Coronary rheothermia: a quasi non-invasive method for controlling bypass patency.

A method based on the principle of thermodilution was developed for a quasi non-invasive permeability control of aortocoronary bypass. An epivascularly-attached thermistor records the cooling of the bypass wall when, following the intravenous injection of 5 to 10 ml of a NaCl solution at 4 degrees C, a bolus of cooled blood passes through the bypass. During cardiosurgical intervention, the thermistor is attached to the venous bridge by one or 2 sutures. The efferent cable goes through the thorax wall and is coupled to a subcutaneously implanted telemetric amplifier unit. The influence of the vessel wall on the perivascular temperature signal, as compared to the intravascular one, was studied in acute and chronic animal experiments. In acute experiments the perivascular peak of temperature was found to be lower than the intravascular one. Continuous measurements over 9 days showed variations in the perivascular signals which must have been due to changes in the thermal capacity of the tissue coupled to the thermistor as well as to changes in resistance caused by a variable extent of scarred area and by the varying water content of the wound bed. These variables will continue to keep rheothermia within the limitations of a method with primarily binary results (= bypass: open or closed). Given stable coupling conditions after full development of the scar around the thermistor, the signal falsification by the then constantly coupled tissue capacity becomes calculable such as to obtain semiquantitative results which, theoretically should vary predominantly with cardiac output.

Animals

[Scoring system for indication for operative correction of funnel chest (author's transl)].

Based on 50 consecutive patients whom we operated for funnel chest, we tried to work out the indications for operative correction by developing a scoring system. In this scoring system we considered not only the depth of of the funnel respectively the depth of the impression, but also all the other disturbances of the organs of the chest resulting from the malformation. The possible accompanying deformities of the thoracic cage were taken into account too. The scoring system demands a more stringent indication.

Adolescent

[The behaviour of the granular alveocytes in chronic pulmonary congestion, pulmonary fibrosis and after extracorporeal circulation (author's transl)].

The granular alveocytes, known to be the site of the production of the surfactant, undergo characteristic changes following chronic pulmonary congestion and the succeeding fibrosis, and after extracorporeal circulation. Congestion is accompanied by cell edema and the breakdown of the lamellar bodies. With fibrosis the cells are shrunken and present with little if any lysosomes. The nuclei are pyknotic or demonstrate karyolysis. Vacuolar degeneration of the lamellar bodies and progressive degeneration of the mitochondria are observed. The extracorporeal circulation damages many granular alveocytes. The degree of damage correlates with the duration of the cardiopulmonary bypass and with the degree of the prepump pathological changes present in the lungs. On the other and the extracorporeal circulation induces in the intact cells enhanced surfactant production, during which the different developmental stages of the lamellar body increasingly accumulate within the cell. In conclusion, pulmonary congestion and fibrosis reduce the activity of the granular alveocytes. The extracorporeal circulation enhances structurally favourable conditions in the granular alveocytes for the increased release of the surfactant in the immediate post-operative phase - a process which could be regarded as an autoregulatory mechanism.

Adult

[beta-Thromboglobulin in plasma in patients with heart-valve diseases and with prosthetic heart valves (author's transl)].

In each 50 patients with rheumatic heart valve diseases and after implantation of prosthetic heart valves and in 20 patients with bioprostheses, beta-thromboglobulin (beta-TG) in plasma was determined. In all cases beta-TG was significantly elevated above the normal range. The levels of beta-TG lay in patients with bioprostheses lower than in the other groups. Bioprostheses are less damaging the thrombocytes than prosthetic heart valves.

Beta-Globulins