Kolorektales Karzinom

Das kolorektale Karzinom stellt in Deutschland die zweithaeufigste Krebstodesursache dar und betraegt bei Maennern ca. 12% und bei Frauen ca. 14%. Die Neuerkrankungsrate lag Ende der 80er Jahre im Saarland fuer Maenner bei 36,6/100.000 Einwohner und fuer Frauen bei 27,9/100.000 Einwohner. Der Haeufigkeitsgipfel liegt um das 65. Lebensjahr mit einem steilen Anstieg ab dem 45. Lebensjahr. Waehrend die Inzidenz fuer das kolorektale Karzinom in der Altersgruppe unter 65 Jahren bei ca. 20/100.000 liegt, betraegt sie in der Altersgruppe über 65 Jahre 337/100.000 (Decosse et al. 1994). Somit ist das Auftreten eines Kolonkarzinoms mit Ausnahme der hereditaeren Krebserkrankungen hauptsaechlich im hoeheren Lebensalter anzutreffen (Greenwald 1990; Pesch et al. 1994; Shankar u. Taylor 1998). Dabei zeigen die altersspezifischen Mortalitaetsraten anschaulich (Tabelle 32.1), dass das kolorektale Karzinom in der Bevoelkerungsgruppe der 75- bis 85-Jaehrigen eine besonders haeufige Todesursache darstellt (Becker u. Wahrendorf 1998). Aufgrund der demographischen Entwicklung mit einem kontinuierlichen Anstieg des prozentualen Anteils aelterer Menschen in der Bevoelkerungsstruktur ist in Zukunft mit einer deutlichen Zunahme des kolorektalen Karzinoms zu rechnen

Anatomical variations in the internal jugular veins of cancer patients affecting central venous access. Anatomical variation of the internal jugular vein

Purpose: Establishing a reliable central venous access is an important procedure in clinical haematology and oncology. The purpose of this study was to determine how anatomical variations in the internal jugular vein (IJV) and its position in relation to the common carotid artery (CCA) in cancer patients affects external landmark puncture. Patients and Methods: In 113 patients with haematological or oncological diseases we examined sonographically potential target regions for placement of a central catheter via the IJV. Results: 36 % of our patients showed anatomical variations in the IJV and surrounding tissue. Conclusions: External landmark puncture may be difficult in a considerable number of patients since the IJV might not be situated in the presumed location anteriorly or laterally to the CCA, or a normal lumen may not be present in approximately ⅓ of cancer patients. This study supports the use of ultrasound-guided techniques for central venous catheters particularly in haematological and oncological patients

Weekly 24-Hour infusion of high-dose 5-fluorouracil plus folinic acid in combination with mitomycin C for the treatment of advanced gastric cancer

Purpose: This study was performed to investigate the activity and safety of high dose 5-fluorouracil (5-FU) given as a weekly 24-hour infusion in combination with folinic acid plus mitomycin C in patients with advanced gastric cancer. Patients and Methods: Chemonaive patients with locally advanced inoperable, recurrent or metastatic gastric cancer were treated with 15 mg/m2 i.v. mitomycin C as bolus on day 1 of a 7-week cycle followed by a 2-hour infusion of folinic acid (500 mg/m2) and a 24-hour infusion of 5-FU (2,600 mg/m2) given on days 1, 8, 15, 22, 29, and 36 as outpatient treatment. Results: Thirty evaluable patients (median age 58 years and median ECOG performance status 1) received 1–4 cycles (median 3). 53% of the patients had liver metastases. Treatment-related toxicity was low with 10% of patients experiencing diarrhea ≥grade 3, 3% mucositis grade 3 and 3% nausea grade 3 (CTC). Hematological toxicity was mild with 13% thrombopenia grade 3 and no leukopenia grade 4. Eleven patients achieved a partial remission (major response rate 37%; 95% confidence interval 22–53%). Median time to progression was 5 months and median overall survival time was 7 months. Conclusion: This regimen is a well-tolerated outpatient treatment for patients with advanced gastric cancer with efficacy being comparable to other chemotherapy protocols

The apoptosis promoting Bcl-2 homologues Bak and Nbk/Bik overcome drug resistance in Mdr-1-negative and Mdr-1-overexpressing breast cancer cell lines

We previously demonstrated that the forced expression of pro-caspase-3 can revert acquired chemoresistance in MT1-Adr breast cancer cells which show a defective activation of the mitochondrial pathway of apoptosis. We now asked whether the manipulation of mitochondrial apoptosis signaling can revert different types of drug resistance, i.e. the resistance due to impaired mitochondrial activation in the MT1-Adr cells and the resistance in MT3-Adr cells which is caused by increased expression of the Mdr-1/p-glycoprotein ABC transporter. Here we show that Bcl-2 overexpression is the underlying cause for the resistant phenotype in the MT1-Adr cells. Overexpression of the apoptosis-promoting Bax homologue Bak or the BH3 only protein Nbk/Bik reverts, as expected, acquired drug resistance in the MT1-Adr cells as recently demonstrated for pro-caspase-3. Moreover, we show that both apoptosis-promoters, Nbk/Bik and Bak, antagonize acquired chemoresistance for epirubicin-mediated apoptosis in MT3-Adr breast cancer cells. Neither drug uptake nor drug efflux were influenced by Bak or Nbk/Bik. Thus, our data show that manipulation of the downstream apoptosis signaling cascade by Bak and Nbk/Bik can overcome not only drug resistance due to mitochondrial apoptosis deficiency (in the MT1-Adr cells) but also classical, i.e. efflux-mediated, resistance for drug-induced cell death in the MT3-Adr cell line. Nbk/Bik and Bak could therefore be target genes to increase chemosensitivity and overcome different types of drug resistance