We have previously demonstrated in primary cancer of the uterine cervix that tumor hypoxia, as determined polarographically, is strongly associated with clinical malignant progression of the disease. Having applied a similar methodological approach to investigate loco-regional relapses, we found a pronounced shift to more hypoxic oxygenation profiles in the recurrent tumors than in the primary tumors. Median pO 2 values in 53 pelvic recurrences were significantly lower than the median pO 2 values of 117 primary tumors of comparable sizes (7.1 ؎ 1.1 mmHg vs. 12.1 ؎ 1.0 mmHg, p ؍ 0.0013). The differences in tumor oxygenation between primary and recurrent tumors mirrored the differences in the patients' 5-year survival probabilities. In the cohort of patients with pelvic relapses, median tumor pO 2 We have shown in primary cancer of the uterine cervix that tumor hypoxia as determined polarographically, not only indicates decreased radiocurability but is generally associated with an aggressive behavior of the disease (Höckel et al., 1993a, b; 1996a, c). Here, we report the results of tumor oxygenation measurements in loco-regional recurrences of cervical cancer. The results further support the thesis that tumor hypoxia is associated with malignant progression (Brizel et al., 1996; Höckel et al., 1996a).
MATERIAL AND METHODS
PatientsSince 1989 we have been prospectively measuring tumor oxygenation in patients with primary cancer of the uterine cervix of Ͼ2 cm clinical tumor size, and in patients with pelvic recurrences that are transvaginally accessible for electrode insertion. The study has been approved by a Medical Ethics Committee. All patients gave informed consent before being enrolled in the study.
TumorsA thorough clinical work-up was performed in all patients with primary and recurrent cancers to completely characterize each tumor. Tumor sizes and locations were assessed in all cases by experienced gynecologic oncologists by inspection, palpation and endoscopy (under anesthesia, if necessary) and pelvic computed tomography (CT) and/or magnetic resonance imaging (MRI) scans. The histological type of all primary and recurrent tumors was verified by core biopsies.
Tumor oxygenation measurementsTumor oxygenation was measured pre-therapeutically with an Eppendorf polarographic system. pO 2 readings were performed in conscious patients in the lithotomy position along linear tracks, first in the subcutaneous fat of the mons pubis followed by tumor measurement. Details of the pO 2 measurement in primary cervical cancer have been reported (Höckel et al., 1991;1993a, b;1996a). Pelvic recurrences had to be (1) visible or palpable transvaginally and (2) of more than 2 cm in size for tumor oxygenation measurements. Two measuring tracks at different intravaginal entry points in the direction of the major tumor mass were taken.Along one track, 25-35 point measurements 0.7 mm apart starting at a tissue depth of 5 mm were recorded. Atmospheric pressure and intravaginal temperature were monitored at the time of the pO 2 ...
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