Erwin M. Röttinger

The value of the tumor marker CA 15‐3 in diagnosing and monitoring breast cancer. A comparative study with carcinoembryonic antigen

To estimate the utility of the tumor‐associated antigen CA 15‐3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15‐3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15‐3 levels with the tumor stage of breast cancer. Both CA 15‐3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow‐up clinic. The CA 15‐3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15‐3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.0001). Although neither CA 15‐3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15‐3 was significantly better than CEA in the detection of breast cancer metastases.

Comparative analysis of apoptosis in HL60 detected by annexin‐V and fluorescein‐diacetate

BACKGROUND Our aim was to compare and evaluate apoptosis formation as detected by propidium-iodide (PI)/annexin-V or PI/fluorescein-diacetate (FDA) as dose-response parameters in a human promyelocytic leukemia cell line, HL60. METHODS In exponentially growing HL60 cells, apoptosis was induced by ionizing radiation, hyperthermia, topotecan, and cytosine beta-D-arabinofuranoside. At 4 consecutive days following induction, apoptosis was detected by double-labelling, either with PI/annexin-V or PI/FDA. Forward and side scatter, red (PI), and green (FDA or annexin-V) fluorescence were measured by flow cytometry. RESULTS While light scatter discriminated between morphologically damaged and undamaged cells, fluorescence differentiated vital, apoptotic, and dead cells. Equal proportions of these three subpopulations were detected by both staining techniques. Occasionally, early and mature apoptoses were identified as distinct clusters. During the 4-day observation period, no pronounced maxima of the apoptotic fractions were obtained with either treatment modality. The gradual increases usually showed a delay of 1-2 days. CONCLUSIONS FDA and annexin-V are equally suitable for detecting apoptosis. Separation improves with time after induction, indicating that, with respect to test specificity, mature apoptoses are superior to early stages. However, the sensitivity towards low rates of apoptosis after weak induction appears limited with both staining procedures.

Comparison of CA 15-3 and CEA in diagnosis and monitoring of breast cancer.

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (> 3ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6%) of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA 15-3 level and tumor stage in breast cancer. CA 15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA 15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the post-care period, carcinoma recurred in 205 patients. Of these 73% had CA15-3 concentrations above 25 U/ml, whereas only 50% had CEA values above 3 ng/ml (p< 0.0001). Although neither CA15-3 nor CEA are sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 is superior to CEA in the detection of breast cancer metastases.

20 MHz ultrasonic imaging for quantitative assessment and documentation of early and late postradiation skin reactions in breast cancer patients

BACKGROUND AND PURPOSE In dermatology high resolution ultrasonic systems proved to be valuable in following up genuine and experimental inflammatory dermatoses. The opportunities of 20 MHz ultrasonic imaging for quantitative assessment of early and late postradiation skin reactions are investigated. MATERIAL AND METHODS Between April and November 1996, 96 high resolution ultrasound examinations of the skin in 29 patients treated for breast cancer at the University of Ulm were analyzed. Total doses between 46 and 60 Gy were applied. The time interval between the completion of radiotherapy and ultrasonic examination was < or =3 months in 18 patients and 6-135 months in 11 patients. For examinations we used a digital high resolution ultrasonic system with a ceramic 20 MHz transducer. Irradiated and non-irradiated skin were compared. RESULTS A change of thickness and texture of the dermis depending on the time interval between the completion of radiotherapy and ultrasonic examination and on the administered radiation dose was found. There were significant differences between irradiated and non-irradiated skin regarding the dermal thickness in early (P < 0.001) as well as in late (P = 0.0018) reactions. Echogenicity of the upper and lower corium of irradiated skin decreased in early and late reaction. In upper corium the greatest reduction of signal intensity occurred in early reactions (P = 0.0001). Early reactions of the lower corium differed significantly from late changes (P = 0.001). Discrepancies between visible skin reactions described by examining physicians and ultrasonically proven changes were obvious mainly in late reactions. CONCLUSIONS There are specific textures of early and late postradiation skin reactions in comparison to non-irradiated skin. High resolution digital 20 MHz ultrasound is non-invasive and quantitative, and in contrast to physical examination, an easy reproducible method for assessing and documenting early and late skin reaction during and after radiation therapy treatment.

Der Einfluß der Therapie auf das Überleben von Patienten mit Pankreaskarzinom Eine Analyse von Einzelfaktoren

Ziel: Behandlungsfaktoren zu identifizieren, die einen Einfluß auf das Überleben von Patienten mit Pankreaskarzinom haben. Patienten und Methode: In einer nichtrandomisierten Studie wurden 38 Patienten ausgewertet, die von 1984 bis 1998 wegen eines Adenokarzinoms des Pankreas behandelt worden waren. Bei 18/38 Patienten war eine Resektion vorgenommen worden. Das Bestrahlungsvolumen beinhaltete den Primärtumor bzw. das Tumorbett und die regionären Lymphknoten. Zusätzlich erhielten 37 Patienten mehrere Chemotherapiezyklen mit Mitoxantron, 5-Fluorouracil und Cis-Platin, entweder intravenös (14/38) oder intraarteriell (23/38). Der Einfluß von Behandlungsfaktoren auf das Überleben wurde untersucht. Die biologisch effektive Dosis wurde mit Hilfe des linearquadratischen Models (α/β = 25 Gy) berechnet bei einem täglichen Wirkungsverlust von 0,85 Gy ab Tag 28. Ergebnisse: Behandlungsfaktoren, die das Überleben beeinflußten, waren die Resektion (p = 0,02), die strahlentherapeutische Behandlungszeit (p = 0,03) und die biologisch effektive Dosis (p < 0,002). Gesamtdosis und Applikationsart der Chemotherapie hatten keinen signifikanten Einfluß. Das strahlentherapeutische Behandlungsvolumen wies eine negative Korrelation (r = −0,5 mit p = 0,06) mit dem Gesamtüberleben auf, ohne daß eine Korrelation zwischen Tumorgröße, Tumorstadium und Behandlungsvolumen nachweisbar war. In der multivariaten Analyse behielt allein die biologisch effektive Dosis mit p = 0,02 ihre Signifikanz. Schlußfolgerungen: Neben der Resektion beeinflußt die biologisch effektive Dosis das Überleben der Pankreaskarzinompatienten. Das Bestrahlungsvolumen soll so klein wie möglich gehalten und eine Unterbrechung der Strahlentherapie soll vermieden werden.Purpose: To identify the impact of treatment factors on overall survival in patients with pancreatic carcinoma. Patients andMethods: We performed a follow-up study on 38 patients with adenocarcinoma of the pancreas treated from 1984 to 1998. 18/38 patients were resected. Irradiated volume included the primary tumor (or tumor bed) and regional lymph nodes. Thirty-seven patients received in addition chemotherapy consisting of mitoxantrone, 5-fluorouracil and cis-platin, either i.v. (14/38) or i.a. (23/38). The influence of treatment related factors on the overall survival was tested. Biologically effective dose was calculated by the linear-quadratic model (α/β = 25 Gy) and by losing 0.85 Gy per day starting accelerated repopulation at day 28. Results: Treatment factors influencing overall survival were resection (p = 0.02), overall treatment time (p = 0.03) and biologically effective dose (p < 0.002). Total dose and kind of chemotherapy had no significant influence. Treatment volume had a negative correlation (r = −0.5, p = 0.06) with overall survival, without any correlation between tumor size, tumor stage, and treatment volume. In multivariate analysis only biologically effective dose remained significant (p = 0.02). Conclusions: Among with surgery, biologically effective dose strongly influences overall survival in patients treated for pancreatic carcinoma. Treatment volume should be kept as small as possible and all efforts should be made to avoid treatment splits in radiation therapy.

Differential proliferation dependence of α and β damage in X-irradiated Chinese hamster cells

AbstractPurposeTo determine quantitatively the influence of altering proliferation rates on clonal survival of asynchronously growing Chinese hamster (CHO) cells after X-irradiation and to evaluate the related contribution of α and β damage.Material and MethodsCell cycle distributions at the time of X-irradiation of CHO cells were assessed by flow cytometry. Clonal radiation survival was established by colony forming assay. Survival data were fitted to the linear-quadratic model and analyzed on the basis of the mean inactivation dose,

Effect of pH and moderate hyperthermia on doxorubicin, epirubicin and aclacinomycin A cytotoxicity for Chinese hamster ovary cells

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Radiation treatment related factors influencing outcome in vulvar cancer patients

.ResultsIncreased S-phases were associated with increased resistance to X-rays. Radiosensitivity as expressed by