Kim Toftager-Larsen

Sexuality after total vs. subtotal hysterectomy.

Background.  The effect of hysterectomy on sexuality is not fully elucidated and until recently total and subtotal hysterectomies have only been compared in observational studies.

Management of ovarian cysts

Background.  The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts.

Plasma tetranectin and ovarian neoplasms

Plasma tetranectin was measured in 67 controls, 121 patients with a benign or malignant ovarian tumor, and 24 patients with another benign gynecologic disease to evaluate the predictive value of plasma tetranectin. A significant reduction of plasma tetranectin was found in every malignant tumor type except for mucinous tumors. Further a significant correlation was found between stage of tumors and plasma tetranectin. Depending on the cutoff level the sensitivity for stage 1 cancer ranged from 52 to 71%. In stage 1 + 2 the sensitivity ranged from 58 to 75% and for advanced cancer (stage 3 + 4) from 80 to 95%. The corresponding specificities ranged from 97 to 84%. Plasma tetranectin may be a useful tool for detecting early stages of ovarian cancer.

MATERNAL‐SERUM‐ALPHAFETOPROTEIN SCREENING FOR FETAL MALFORMATIONS IN 28062 PREGNANCIES

Abstract. From 1st March, 1980 and up to 29th February 1984 a multicenter serum α‐fetoprotein (S‐AFP) screening project was carried out for the detection of severe fetal malformations. S‐AFP was determined by a radio‐immunoas‐say in 28062 pregnant women between the 16th and 20th week of gestation. Patients with elevated S‐AFP values, e.g. above 95 percentile, were examined further with a second S‐AFP and by ultrasound scan. 244 amniocenteses (0.9%) were carried out to detect 62 malformations (21 anen‐cephalies, 14 spina bifidas, 2 encephaloceles, 7 omphaloceles, 5 gastroschises, 4 chromosome abnormalities and 9 other malformations). Fifteen of the 16 cases of spina bifida could not be verified by ultrasound scan, whereas all other malformations except chromosome abnormalities were confirmed by ultrasonography. Two cases of spina bifida and one case of skin‐covered encephalocele had normal S‐AFP concentrations and were therefore not detected. There were no definitive false‐positives, e.g. therapeutic abortion of a normal fetus. Our conclusion is that a nationwide S‐AFP screening should be recommended.

Immunoreactive inhibin-production in post-menopausal women with malignant epithelial ovarian tumors

In post-menopausal women with a malignant epithelial ovarian tumor the follicle stimulating hormone (FSH) level was found to be significantly lower compared with healthy controls. We demonstrated immunoreactive (i.r.) inhibin in 20% of controls which was elevated to 60% of women with an ovarian tumor and correlating strongly to FSH in the tumor group (P = 0.0002). Steroid hormone levels were comparable in the two groups. In women with ovarian tumors the survival time for the i.r. inhibin-producing women was found to be 4.6 years compared with 0.9 year, or 5.1 times longer than in the non-producing women (P = 0.002). The site of i.r. inhibin production in these post-menopausal women is unknown, but i.r. inhibin production by the developing ovarian tumor or by the post-menopausal ovary may be regarded as a defense mechanism against an elevated gonadotrophin level (the gonadotrophin theory) which would promote further tumor growth. The recent suggestion that the alpha subunit of inhibin is a tumor suppressor gene is consistent with these results. The serum i.r. inhibin or alpha subunit concentrations might be used as an aid to diagnosis or as a prognostic indicator of survival in women with an ovarian carcinoma.

Concanavalin A reactivity pattern of human amniotic fluid AFP examined by crossed affino-immunoelectrophoresis. A definite test for neural tube defect?

The percentage of alpha‐fetoprotein (AFP) not reacting with concanavalin A (con A) was determined by crossed line affino‐immunoelectrophoresis in amniotic fluid from 25 pregnancies with neural tube defects (NTD) and other fetal abnormalities giving rise to elevated AFP levels, and from 128 pregnancies with normal outcome. The percentage of con A non‐reactive AFP is significantly lower in the presence of fetal abnormalities (mean 3.4 %, range: 0.0–6.3, n = 23, compared to the percentage found in normal pregnancies (mean 17.2 %, range: 6.6–35.8 %, n = 128). In amniotic fluid samples from normal pregnancies, the percentage of con A non‐reactive AFP in 84 cases with total AFP levels lying within the 95 % reference interval was not significantly different from the percentage found in 44 cases with levels above the 95 % reference interval. The percentage of non‐reactive AFP in fetal serum and cerebrospinal fluid was of the same magnitude as found in amniotic fluids of pregnancies with fetal abnormalities. It is concluded that analysis of the percentage of con A non‐reactive AFP by crossed line affino‐immunoelectrophoresis is a simple, reliable and apparently diagnostic test for NTD and ether abnormalities with leakage of fetal serum or cerebrospinal fluid into the amniotic fluid. The test should therefore be used in all cases with only marginally elevated AFP levels, so false positives may be avoided.

The post-operative gonadotropin level in post-menopausal women with epithelial ovarian cancer

Serial estimates of the post-operative hormone levels were made in 15 women subjected to oophorectomy because of ovarian carcinoma. All women were post-menopausal. Pre-operatively, they had significantly lower follicle stimulating hormone (FSH) levels compared with an age-matched control group. Blood samples were collected after a median time of 8 months (139-378 days). After oophorectomy, significantly higher FSH values were found (P = 0.0002), whereas the luteinizing hormone (LH) values were not significantly changed. The inhibin, estradiol and progesterone values were found to be significantly lowered compared with the pre-operative sample. Total and unbound testosterone levels were significantly lower while dehydroepiandrosterone sulphate (DHEAS) and androstenedione levels were unchanged compared with the original sample and compared with controls. Most likely, estradiol and progesterone are produced by the epithelial malignant tumors, as the post-operative values are completely comparable with the primarily included healthy controls. The FSH is suppressed by inhibin and only to a minor degree by the steroid hormones as indicated by the correlation coefficients. Of great interest is the question whether inhibin production is random, or defensive, lowering the gonadotropin levels or influencing tumor growth in some hitherto unknown fashion.

Ovarian carcinoma serum markers and ovarian steroid activity — is there a link in ovarian cancer? A correlation of inhibin, tetranectin and CA-125 to ovarian activity and the gonadotropin levels

In a previous study, we have demonstrated that inhibin-production may be associated with improved survival and, also, that tetranectin (TN) is a valuable prognostic marker in ovarian epithelial cancer. We investigated the possible correlation between inhibin, tetranectin, CA-125, ovarian steroid activity and the gonadotropin levels. Preoperative serum levels of the tumor markers inhibin, tetranectin (TN) and CA-125 were measured and related to ovarian steroid function and the pituitary-gonadal axis (gonadotropin levels) in 28 postmenopausal ovarian cancer patients. The following median levels and 95% confidence limits were demonstrated for the tumor markers: Inhibin 0.4 U/l (0.2-0.9), TN 8.9 mg/l (6.8-9.2), CA-125 160 kU/l (75-687). A significant inverse correlation was demonstrated between inhibin and the gonadotropins. The Spearman correlation coefficients showed a highly significant correlation of inhibin with the examined ovarian steroid hormones except DHEAS which also has a suprarenal component. This indicates a synthesis of inhibin and the steroid hormones from the same cell compartment as known from the normal ovary and an apparently intact negative feed back mechanism. Inhibin may be produced in the normal ovary as a defense mechanism against an elevated gonadotropin level and inhibin acts by lowering the gonadotropins or by altering their biological activity. Elevated values of the tumor markers TN and CA-125 due to gonadotropin stimulation could not be demonstrated but a significant inverse correlation between TN and CA-125 was confirmed.

NON-OBSTRUCTIVE CECAL DILATATION AND PERFORATION AFTER CESAREAN SECTION

A case of non‐obstructive cecal dilatation and perforation after cesarean section is reported, with a review of the literature on the diagnosis and management of this entity. Fifteen cases have been described. Attention is called to this rare complication and to the accompanying pseudo‐obstructive syndrome, the diagnosis of which is important in order to avoid cecal perforation. Non‐obstructive cecal dilatation is a lifethreatening complication to cesarean section, and immediate surgical intervention is important.

Hormonal factors and prognosis in epithelial ovarian cancer: a multivariate analysis

When a significantly lower follicle stimulating hormone (FSH) level was found in patients with epithelial ovarian carcinoma, it was decided to analyze the influence of hormonal factors on prognosis. Thirteen factors were tested for prognostic significance in 35 women with epithelial ovarian carcinoma. Age, FIGO-stage, histopathological grade, residual tumor, treatment, gonadotrophins and steroid hormones were tested. By univariate log-rank testing a significantly shorter survival time was found for patients with ascending FIGO-stage, residual tumor mass, estradiol < 0.10 nmol/l, progesterone < 2.0 nmol/l and DHEAS < 1300 nmol/l. In the Cox model the independently significant prognostic factors found were residual tumor mass (P < 0.001) with a risk estimate of 2.65, progesterone (P < 0.05) with a risk estimate of 0.29 for a progesterone level > 2.0 nmol/l and total testosterone (P < 0.03) with a risk estimate of 0.29 for a total testosterone level > 1.15 nmol/l. The present findings, together with the assumption that an elevated gonadotrophin level may induce ovarian tumor growth (the gonadotrophin theory), earlier findings of estrogen and progesterone receptors in human ovarian cancer, and the in vitro demonstration of gonadotrophin-growth-stimulation of human malignant epithelial tumors, justify a thorough investigation of the interaction between steroid hormones and receptors, gonadotrophins, tumor bulk and survival in future research protocols.