Modulation of tumor-induced lethality after pneumoperitoneum in a mouse model.

BACKGROUND: To the authors' knowledge, a generally accepted approach to prevent increased intraabdominal tumor implantation after laparoscopic cancer surgery does not exist. METHODS: One week after establishing an ovarian carcinoma cell line in black mice intraabdominally (n = 156), a carbon dioxide pneumoperitoneum (Group 1: n = 78) was administered. The effect of this procedure on tumor-induced lethality and the therapeutic effect of mitoxantrone and taurolidin mixed with heparin and sodium chloride was investigated. The different drugs were added immediately after the release of the pneumoperitoneum and after 48 hours. The 78 control animals received the drugs at the same time without preexisting pneumoperitoneum. Survival time was registered. RESULTS: The survival time was reduced significantly in all pneumoperitoneum groups compared with the corresponding control group without pneumoperitoneum. The effect of mitoxantrone on survival time (mean, 62.08 days) was diminished significantly by the application of a pneumoperitoneum (mean, 34.27 days). Taurolidine/heparin appeared to have a positive effect on survival time only in the case of a previous pneumoperitoneum (mean of 21.12 days vs. mean of 16.04 days in the pneumoperitoneum control group; P < 0.001). CONCLUSIONS: The induction of a pneumoperitoneum appears to decrease survival time by increasing tumor cell growth and decreases the efficacy of intraperitoneal chemotherapy. The effects of pneumoperitoneum appear to be reduced by the use of heparin/taurolidine, which theoretically blocks extracellular matrix binding domains and inhibits the production of interleukin-1.

Determination of the cellular retinoic-acid-binding protein in dysplastic epithelia of the cervix uteri, differentiated into apo and holo forms.

PURPOSE: The appearance of the cervical mucosa is regulated by different factors including retinoic acid. Hormone-dependent alteration of the cervix uteri mucosa is accompanied by a decrease or increase of cytoplasmatic retinoic-acid-binding protein (CRABP). To elucidate whether this hormone-dependent alteration of CRABP is preserved in the case of neoplasms of the cervix uteri, we measured the level of total and apo-CRABP in normal and neoplastically transformed cervical cells. METHODS: In a prospective pilot study, standardised biopsies of normal epithelium and cervical intra-epithelial neoplasm grade 3 (CIN III) were taken from 24 patients. A newly developed method was used to determine the intra-epithelial level of apo- and total CRABP. RESULTS: The concentration of total CRABP in normal squamous epithelium compared with that in intra-epithelial neoplasm grade 3 is very significantly lower in the CIN III areas (normal: 3.66 +/- 1.46 pmol/ mg wet weight +/- SD; CIN III 1.43 +/- 0.59 pmol/mg P < 0.01). In addition CRABP in the apo form is lower in normal than in neoplastic epithelium (Wilcoxon test for paired non-parametric values: P < 0.05; mean for all patients: normal: 1.65 + 0.82 pmol/mg; CIN III: 1.14 +/- 0.23 pmol/mg). CONCLUSION: From our results we conclude that, in neoplastically transformed cells, the hormone-dependent CRABP cycle is interrupted. Whether this has consequences for the further development of the neoplastic cells has to be elucidated.