O. Dapunt

Decreased plasma tryptophan in pregnancy

Objective To examine levels of serum tryptophan and its degradation product kynurenine in uncomplicated pregnancy, according to the week of pregnancy and the concentrations of neopterin. Methods Plasma was analyzed from 45 healthy pregnant women (15 in each trimester), 15 healthy puerperas, and 20 nonpregnant controls. Tryptophan and kynurenine were measured by reverse-phase, high-performance liquid chromatography, and neopterin by radioimmunoassay. Results In healthy pregnant women, tryptophan values decreased (median first trimester: 72 μmol/L; second trimester: 51 μmol/L; third trimester: 46 μmol/L; P < .001) in a manner correlated with the duration of pregnancy (Spearman rank correlation coefficient rs = −0.771, P < .001) and normalized in the puerperium (median 60 14mol/L). No change in kynurenine, a tryptophan degradation product, was observed, but the ratio of kynurenine to tryptophan increased during pregnancy and correlated positively with gestational age (rs = 0.714, P < .001). In addition, an inverse correlation existed between neopterin and tryptophan concentrations (rs = −0.566, P < .001), as well as a positive one between neopterin and the kynurenine to tryptophan ratio (rs = 0.660, P < .001). Conclusion Tryptophan levels decrease during normal pregnancy and the decrease may be related to immune activation phenomena.

Significance of thrombocytosis in patients with epithelial ovarian cancer

Abstract OBJECTIVES: Our objective was to determine the relevance of a preoperative platelet count in ovarian cancer. Special interest was directed to a possible prognostic significance of thrombocytosis in this disease. STUDY DESIGN: Charts of 130 patients with epithelial ovarian cancer were reviewed retrospectively. Survival analyses were performed with the Kaplan-Meier method. Differences in survival were examined according to Mantel and Breslow. Platelet counts were furthermore correlated to other clinical parameters. For this purpose the Spearman rank test and a stepwise logistic regression model were used. Data comparison was accomplished with the Mann-Whitney U test and the χ 2 test. RESULTS: Prevalence of thrombocytosis was 38%. No differences in survival between patients with or without thrombocytosis was found. Volume of ascities and hemoglobin concentrations were independently associated with thrombocytosis (p = 0.002 and p = 0.004, respectively). CONCLUSIONS: Thrombocytosis is not a useful prognostic factor in ovarian cancer. Elevated platelets are predominately associated with the presence of ascites and marked anemia. (A M J O BSTET G YNECOL 1994;170:549-54.)

Coronary endothelial injury after local occlusion on the human beating heart

BACKGROUND Occlusion of coronary arteries during beating heart surgery bears the potential for mechanical trauma to the arterial wall with consequent endothelial injury. The aim of this study was to elucidate the effects of local occlusion on the beating heart in human coronary arteries. METHODS Coronary arteries of patients with dilated cardiomyopathy (n = 7) or ischemic heart disease (n = 10) undergoing heart transplantation were locally occluded after starting cardiopulmonary bypass. Immediately after excision of the diseased heart, the vessels were fixed. Unoccluded segments served as controls. Integrity of endothelial lining was observed with scanning electron microscopy. RESULTS Scanning electron microscopy revealed significantly more severe endothelial injury in the area of occlusion than in the adjacent, not manipulated control segments. In the region of local occlusion, plaque rupture was noted in three of 34 atherosclerotic vessel specimens, injury to side branches was evident in two of 44, and local microthrombus formation was evident in six of 44 samples. CONCLUSIONS Local occlusion of human coronary arteries during beating heart coronary surgery may cause focal endothelial denudation, local microthrombosis, atherosclerotic plaque rupture, and injury to target vessel side branches.

Tumor marker CA-125 in tissues of the female reproductive tract and in serum during the normal menstrual cycle

OBJECTIVE To further elucidate the origin of the physiological CA-125 amounts that lead to cyclic changes in CA-125 serum levels in normally menstruating women. DESIGN Fifty-three normal endometria, 13 fallopian tubes, 25 ovaries, and nine isolated corpora lutea were prospectively investigated for their CA-125 content in a sandwich solid-phase RIA and by immunohistochemistry. In addition, endometrial CA-125 tissue content was compared with the actual CA-125 serum levels of the study patients. RESULTS Cytosolic CA-125 concentrations were 20-fold and twofold higher in the endometrium than those measured in the ovary and the fallopian tube, respectively. Moreover, only in the endometrium did CA-125 content show significant cyclic changes, with the highest concentrations during the early proliferative and middle secretory phase. The lowest tissue concentrations were measured during the early secretory phase. Furthermore, during the early and middle secretory phases cytosolic CA-125 was negatively associated with CA-125 serum levels. In immunohistochemistry, marked distributional changes in OC-125 reactivity were revealed in the basalis and the functionalis throughout the menstrual cycle and the postovulatory loss of CA-125 expression was found to be strongly connected with early secretory transformation of glandular epithelium. CONCLUSION Our findings indicate that the CA-125 amounts responsible for cyclic changes in serum levels in normally menstruating women seem to be a product of normal endometrium.

Prognostic value of CD44 splice variant expression in ovarian cancer

In 44 ovarian cancers, CD44 variant (CD44v) expression was investigated immunohistochemically using a variant-specific polyclonal antibody. Patients with CD44v-positive carcinomas had a significantly shorter disease-free survival than patients with CD44v-negative tumors. Overall survival was also significantly reduced for stages III and IV of the International Federation of Gynecology and Obstetrics. Furthermore, a highly significant inverse correlation was observed between CD44v expression and preoperative platelet count. Urinary neopterin concentration, a marker of cell-mediated immunostimulation, did not differ between CD44v-positive and -negative ovarian cancer patients. Moreover, in seven ovarian carcinoma cell lines, modulation of CD44v expression was analyzed by living cell radioimmunoassay. Interferon-alpha, interferon-gamma, tumor necrosis factor, transforming growth factor-beta, all-trans retinoic acid and cisplatin did not affect CD44v expression.

Circulating immunostimulatory protein 90K and soluble interleukin-2-receptor in human ovarian cancer

The tumor‐associated antigen 90K is thought to play an important role in cellular immune defense against malignant cells. It is therefore of interest to investigate whether circulating 90K could be used as a prognostic variable in ovarian cancer, and whether this immunostimulatory antigen is related to other parameters known to be involved in the cellular immune response. In the present retrospective study, circulating levels of antigen 90K were measured before primary surgery in 152 ovarian‐cancer patients. A very close association between antigen 90K and s‐IL‐2R concentrations was pointed out in a stepwise logistic regression model. Univariate analysis of overall survival revealed that antigen 90K and s‐IL‐2R were associated with poor prognosis. In the multivariate Cox regression, however, neither antigen 90K nor s‐IL‐2R retained independent prognostic significance. Urinary neopterin was shown to be the only independent prognostic variable among the “immunological parameters” investigated. Additionally, residual disease after primary tumor debulking and histopathologic tumor grade were the most prominent clinico‐pathologic parameters for the independent prediction of poor clinical outcome in ovarian‐cancer patients.

CA 125 in the Serum and Tissue of Patients with Gynecological Disease

SummarySerum levels of CA 125 were determined in 239 patients suffering from gynecological malignancies. The upper limit for normal was 35 U/ml. Raised levels were found in 82% of patients with primary ovarian carcinoma, and in 29% of those with benign ovarian tumors. The values from patients with ovarian carcinomas in partial or complete remission were compared with those from patients with progressive disease. The former group had elevated levels in 19% compared to 89% in the latter group. Fifty-four percent of the values in progressive cervical carcinoma and 41% of the levels in progressive endometrial carcinoma were greater than 35 U/ml. High CA 125 levels were found in the cytosol of placenta, ovarian carcinoma, cervical carcinoma, and in ascitic fluid; correlation with serum levels was satisfactory. Even though CA 125 is of limited specificity for ovarian cancer, serum levels are important for follow up care and for the early detection of recurrences.

The prognostic value of nuclear roundness and neopterin in ovarian cancer

The prognostic value of clinical factors, morphometric features and neopterin, a marker for macrophage activation, was investigated retrospectively in 68 ovarian carcinoma patients. Nuclear roundness was a good predictor of patient survival. About 50% of our patients showed neopterin concentrations above the cut-off level of 275 mumol/mol creatinine. Interestingly, those patients with elevated urinary neopterin concentration, and thus displaying a sign of activation of cell-mediated immunity, had a shorter survival than those with normal concentration. Applying a multivariate Cox regression analysis, the only independent parameters predicting patient survival were FIGO stage, residual disease, nuclear roundness and neopterin.

Inhibition of the estradiol-induced growth of cultured human breast cancer cells by the anti-estrogens tamoxifen, desmethyl-tamoxifen, 4-hydroxy-tamoxifen and enclomiphene

The growth effects of tamoxifen (T), desmethyl-tamoxifen (dMeT), 4-hydroxy-tamoxifen (OHT) and enclomiphene (Clo) on cultured human breast cancer cell lines have been related to published binding affinities for the estrogen receptor. Only in cells which were stimulated by estrogens did these anti-estrogens markedly inhibit growth. In both estrogen sensitive cell lines tested, 734 B and ZR 75.1, the anti-estrogen activity showed the identical rank: OHT much greater than Clo approximately equal to T = dMeT; this anti-proliferative potency agrees with reported affinities of these compounds for the estrogen receptor. In culture media containing defined amounts of estradiol we observed that a 10,000-fold molar excess of OHT was required to inhibit the estradiol-induced growth, but the estradiol-independent proliferation was not affected.

Ovarian preservation in the surgical treatment of cervical carcinoma

OBJECTIVES In the surgical treatment of cervical carcinoma the conservation of ovaries in premenopausal women is a common procedure. To date, however, there have been no controlled studies to prove that the risk of recurrence or death from disease is not elevated among women who do not undergo oophorectomy. STUDY DESIGN We performed a matched pairs analysis according to the tumor volume, comparing the outcomes of patients with in situ conservation of >/=1 ovary with those of control subjects who underwent bilateral oophorectomy. From among 658 patients, 150 pairs with International Federation of Gynecology and Obstetrics stage I disease were matched. Kaplan-Meier survival curves were compared with the log rank test. RESULTS Among patients who retained their ovaries 5- and 10-year overall survival rates were 98% and 96%, respectively, versus 97% and 97% for the oophorectomy control group. The corresponding figures for progression-free survival were 95% and 94%, respectively, versus 97% and 93%. Outcomes were equal with sufficient power to detect a 10% difference. Three of 214 patients with conservation of ovaries (1.3%) subsequently required oophorectomy, all because of benign ovarian diseases. CONCLUSIONS Our results confirm that ovarian conservation is safe in International Federation of Gynecology and Obstetrics stage I disease and that the occurrence of subsequent complications in ovaries retained in situ is rare.