[Effect of therapy on survival of patients with pancreatic carcinoma]. / Der Einfluss der Therapie auf das Uberleben von Patienten mit Pankreaskarzinom. Eine Analyse von Einzelfaktoren.

PURPOSE: To identify the impact of treatment factors on overall survival in patients with pancreatic carcinoma. PATIENTS AND METHODS: 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 (alpha/beta = 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.

Distinct area distribution differences of micronuclei induced by clastogenic and aneuploidogenic chemicals in the bone marrow of the CD-1 mouse.

To distinguish between aneuploidogenic and clastogenic effects of test chemicals, area distributions of micronuclei (MN) in polychromatic erythrocytes (PE) from the mouse bone marrow were measured using an image analysis system. Triethylenemelamine (TEM), cytosine-beta-D-arabinofuranoside (ara-C), urethane (URT), cyclosphamide (CP), mitomycin C (MMC), colcemid (COL) and tubulazole C (TUB) were investigated for the induction of micronucleus area distributions. The area distribution of micronuclei of untreated mice was also determined. Reproducible small differences between the clastogens and the aneuploidogens were observed after measuring 1100-1200 micronuclei. A common feature of the distribution curves was a shoulder region in the same area range for all clastogens. The aneuploidogens COL and TUB showed a plateau (= wide peak) in this clastogenic shoulder region. For all clastogens, the integrated area of shoulder over a fitted function (shoulder strength) was evaluated. MMC and CP, thought to have some aneuploidogenic potential, showed an increased shoulder strength compared to TEM, ara-C and URT. The control area distribution had no similarities to the area distribution of either clastogens or aneuploidogens. In a further experiment, we attempted to correlate the size of micronuclei determined after treatment with the aneuploidogenic chemicals to the size of whole chromosomes. Micronuclei found by image analysis which bear chromosome-like structures (judged by light microscopy) were manually identified. This selection of micronuclei was area-distributed to determine the mean size of these micronuclei. None of the peaks and plateaus in the area distributions obtained with the aneuploidogenic chemicals could be attributed to the size of a chromosome.

Micrometástasis en médula ósea en cáncer colorrectal / Micrometastasis in bone marrow in colo-rectal carcinoma

Los métodos de diagnósticos convencionales son insuficientes para comprobar las micrometástasis o la diseminación de células tumorales. Con la ayuda de nuevos métodos inmunocitoquímicos, se perfilan nuevas posibilidades para el diagnóstico de las micrometástasis, puesto que ellos pueden diferenciar células histogenéticamente distintas. El anticuerpo monoclonal Cytokeratin 2 (MAK CK2), que marca el componente 18 de citokeratina del carcinoma colorrectal (CCR), es el más adecuado para demostrar las micrometástasis en la médula ósea. Nosotros hemos podido identificar células CK2 - positivas, con los carácteres de micrometástasis, en las médulas óseas de 22 enfermos, de un total de 82 pacientes con CCR. Se analiza el hallazgo de las micrometástasis, mediante dicho método, en función de los factores dados por el paciente y el tumor. Esto es, edad y sexo, localización y tamaño del tumor primario, presencia de adenopatías, de metástasis a distancia y según los grados histopatológicos de malignidad

Comparison of single/multiple-dose protocols using triethylenemelamine and procarbazine hydrochloride for the mouse bone marrow micronucleus test.

Treatment of mice with a single dose of either 4.8 mg/kg of triethylenemelamine (TEM) or 348 mg/kg of procarbazine hydrochloride (PC) induced higher frequencies of micronucleated polychromatic erythrocytes (MPE) after 48 h than after 24 h. The same observation was made when animals were treated with 1.6 or 8 mg/kg of TEM or 116 or 580 mg/kg of PC for 2 consecutive days (double-dose protocol). Surprisingly, the third dose of either 1.6 or 8 mg/kg of TEM caused lower MPE frequencies at the 72-h than at the 48-h sampling time. The observation that lower MPE frequencies after 72 h were also accompanied by reduced bone marrow toxicity might have reflected a drug-related adaptive reaction of the animals, for example the induction of detoxifying enzymes. Mean MPE frequencies as well as bone marrow toxicity were also slightly decreased after the third dose of either 116 or 580 mg/kg of PC, but statistical analysis showed no differences between the 48-h and the 72-h sampling times as regards the MPE frequencies and bone marrow toxicity. In addition to the high mean MPE frequency observed after 2 doses of 116 mg/kg of PC at the 48-h sampling time, a late increase in micronucleus induction was also seen after triple dosing at the 96-h sampling time. The present experiments with TEM and PC showed similar sensitivity for the multiple-dose assays when compared with the single-dose micronucleus test. In the case of the triple-dose assay, bone marrow toxicity proved to be a critical factor for appropriate dose selection. The computerized image analysis system was a convenient and time-saving tool for the automatic scoring of large quantities of cells for micronuclei as well as for the evaluation of bone marrow depression from the entire cell population analyzed for micronuclei.

Influence of insecticide treatment on German cockroach (Dictyoptera: Blattellidae) movement and dispersal within apartments.

Two similar studies were done to investigate effects of insecticide treatments on German cockroach, Blattella germanica (L.), movement and dispersal within individual units in multifamily housing. In the first study, Whitmire PT-565 Pyrethrum Insect Fogger (pyrethrins), Diazinon 4E (diazinon), Protector (permethrin), and Baygon 1.5 (propoxur) did not induce any significant changes in cockroach distribution, and rates of movement within apartments decreased. In the second study, populations treated with sublethal doses of pyrethrins and resmethrin settled to their original distribution 24 h after treatment. Results from both studies indicate that thorough insecticide applications do not significantly affect German cockroach population dispersal or movement patterns within apartments.

[Bone marrow micrometastases in colorectal cancers]. / Knochenmarksmikrometastasen bei kolorektalen Karzinomen.

To date, the detection of individual micrometastases or disseminated tumor cells has not been possible with conventional diagnostic procedures. With the aid of new immunocytochemical investigation, however, histogenetically different cells can now be detected in the bone marrow. The monoclonal antibody, cytokeratin component 18, is most suitable for the detection of micrometastases from colorectal carcinoma. In 22 out of 82 patients with colorectal carcinoma, we were able to detect CK2-positive cells. The incidence of these "micrometastases" is represented as a function of primary tumor size, lymph node involvement, distant metastasis, and degree of malignancy of the tumor, age and sex of the patient, and tumor localization.