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The expression of the MDR1 gene has been shown to correlate with tumor aggressiveness and oncogenic activation both in experimental tumor models and in human clinical specimens In order to verify whether this association also takes place in ovarian carcinoma, we studied tumor samples from 39 patients by means of immunohistochemistry for the overexpression of P-glycoprotein (MDR1), nm23, c-erb-B2 and p53. MDR1 (p = 0.023), nm 23 (p = 0.037) and c-erb-B2 (p = 0.015) were expressed significantly more in specimens from patients with advanced stage of disease. There were no differences in p53 expression between both groups of patients. Furthermore, we found a significant coexpression of MDR1 and nm23 (p = 0.028), and of MDR1 and c-erb-B2 (p = 0.0077). There was no association between the expression of the MDR1 gene and p53. These results parallel those previously reported by us for mammary carcinoma, and seem to indicate that expression of the multidrug resistance gene (MDR1) is inherent to the development of the malignant phenotype in several human tumors.

Twenty-four advanced (surgical stage III and IV) ovarian carcinomas and 15 borderline ovarian tumours were studied for the overexpression of nm23 and HER-2/neu (c-erb-B2) by means of immunohistochemistry on sections from routinely processed, paraffin-embedded, archival tumour blocks, using the NCL-nm23 and the NCL-CB11 monoclonal antibodies and the streptavidin-biotin-peroxidase technique. Significantly more advanced ovarian carcinomas (p = 0.034) expressed high levels of nm23 when compared to borderline tumours. HER-2/neu (c-erb-B2) expression, as could be expected, was also significantly more frequent in advanced ovarian carcinomas (p = 0.006). We were not able to find the previously reported association between nm23 and HER-2/neu overexpression in our tumours. Our results on nm23 overexpression in ovarian cancer are coincident with those previously reported using nm23-mRNA measurements on fresh ovarian tissues. Thus, ovarian carcinoma seems to belong to the group of tumours, like colon carcinoma and neuroblastoma, in which nm23 overexpression is associated with a more malignant phenotype. Immunohistochemistry performed on archival samples from ovarian carcinomas seems adequate for the demonstration of nm23 overexpression in ovarian cancer. This opens the possibility for larger studies on series of patients with a closed follow-up, which could help to establish the role of this gene in this kind of tumour.

Although germ cell tumors arising from adnexa are relatively frequent among young women, diagnosis is often delayed by omitting basic diagnostic procedures. This case report highlights the importance of using the available diagnostic tools beginning from the simplest one, i.e., physical examination, to the most sophisticated and reliable one (ultrasonography). Diagnostic pitfalls and management of a massive ovarian tumor in an 18 year-old woman are reported.

Between January 1980 and June 1991, 56 patients with Stage I ovarian carcinoma of different histological varieties were submitted to a second-look laparotomy (SLL) at the University Clinic (Hospital de Cruces) of Bilbao, Spain. The operation was performed upon all patients one year after initial surgery, after completion of adjuvant chemotherapy, or after one year of observation in those cases that were not treated postoperatively. The SLL was negative in 55 of cases and positive in one. The median follow-up after SLL was 59 months. Of the 55 negative cases, four (7.3%) have had a recurrence of their tumor during their long-term follow-up. Three had epithelial tumors and had received complete postoperative chemotherapy, and the fourth was a dysgerminoma. The three patients with epithelial tumors have died under second-line chemotherapy, whereas the dysgerminoma patient is responding well to rescue polychemotherapy. In view of these results, it is useless and probably unethical to perform second-look laparotomy in Stage I ovarian carcinoma if the initial staging was properly performed.

Endodermal sinus tumor (EST) of the ovary is extremely rare and little information exists about therapy and the role of second-look laparotomy in the management of this entity. A case of EST of the ovary in a 21 year old woman is reported. She received conservative surgery and six courses of combination therapy consisting of Vincristine, Actinomycin D and Cyclophosphamide before second-look laparotomy. Due to progression of the disease second-line polychemotherapy with Vinblastine, Bleomycin and Cisplatin was administered. This new regimen reduced the alpha-fetoprotein to normal levels although the patient was not free of disease on second-look laparotomy. Precise guidelines for the management of this disease, especially in advanced stages, are still lacking.

Between January 1980 and December 1990, 107 ovarian carcinoma patients in clinical complete remission were submitted to a second-look laparotomy at our department. Borderline carcinomas were excluded from the study. Second-look laparotomy was negative in 78.5% of the cases (84 patients). During the follow-up period after the second-look-laparotomy (mean 59 months, range 6 to 120), a recurrence of the tumour was diagnosed in 7 patients (8.4% false-negative rate). This took place after a mean time of 39 months following the previous negative second-look (range 8 to 108). Three of the recurrences were localized in the pelvis, two in the upper abdomen and two in the paraaortic and supraclavicular lymph nodes, respectively. All patients with a recurrence belonged to the group having received adjuvant chemotherapy for one year after initial surgery. At the present time we lack any means to anticipate which patients with a negative second-look will eventually show a recurrence of their tumour.

In 1980, second-look laparotomy was introduced simultaneously into the treatment regimen for ovarian carcinoma at the two main referral centers of northern Spain. First-line chemotherapy after initial surgery was, however, different at both hospitals. At one of them (Bilbao), a combination involving the use of cisplatin was employed (cyclophosphamide 600 mg/m2, Adriamycin 45 mg/m2, and cisplatin 80 mg/m2 i.v. on day 1), whereas the patients of the other hospital were treated mainly with single-agent chemotherapy (melphalan 0.2 mg/kg p.o. on days 1-5) and never with a cisplatin combination as first-line therapy in any case. In all, 92 patients (42 stage I, 14 stage II, 33 stage III, and 3 stage IV) could be treated during the study period with optimal surgery (complete tumor excision or largest residual tumor less than 2 cm in diameter). This was followed by adjuvant chemotherapy for 12-18 months in all cases, except for 18 patients with a stage Ia borderline or G1 tumor. The latter were merely kept under observation until their second-look laparotomy after 1 year of negative follow-up. All of the 74 patients who received adjuvant chemotherapy, of whom 36 with cisplatin and 38 without, were clinically disease free after at least twelve courses of treatment and had a second-look laparotomy performed. This was positive in 33.3% of the cases after cisplatin-containing therapy and in 26.3% of the cases after cisplatin-free therapy. This difference is not statistically significant. The mean follow-up period after negative second-look was 34 months. The long-term results of both patient groups were comparable as far as rate of positive second-look laparotomies and survival rate, overall and stage for stage are concerned. The use of cisplatin did not result in any significant therapeutic improvement. It was uniformly bad tolerated by the patients and carried higher cost, since all patients had to be hospitalized for treatment.

From 1976 to 1989, 29 cases of ovarian theca cell tumors were diagnosed at the Pathology Department of our Hospital. Their clinical and histologic features were reviewed. The main presenting symptom in postmenopausal patients was uterine bleeding, whereas in premenopausal women, abdominal swelling and the findings of ultrasonographic examination were the diagnostic keys. Different surgical procedures were the cornestone of treatment, although in 12 cases the indication for surgery was not apparently related to an adnexal condition.

Sera from 52 ovarian cancer patients undergoing chemotherapy and second look operation were studied. CA 125, CA 15.3 and CA 19.9 assays were performed during chemotherapy and prior to relaparotomy. Twenty-six patients (50%) had no evidence of disease whereas 2 (3.8%) and 24 (46.1%) had microscopic and macroscopic disease. In general although the predictive value of an elevated CA 125 or CA 15.3 level is excellent, a normal value (less than 35 U/ml) has limited significance. Moreover, we found no improvement in negative predictive and positive predictive value by adding the determination of CA 19.9.

We have analyzed 37 cases of simultaneous appearance of carcinoma in the ovary and endometrium. This paper deals with the question of whether they should be considered stage III endometrial carcinomas, stage II ovarian carcinomas or independent primary tumors. The cases were grouped according to their histology as endometrioid ovarian carcinomas with endometrial carcinoma (group A), same carcinoma, but not of endometrial origin in both organs (group B) and histologically different concomitant carcinomas of ovary and endometrium (group C). Although our series was small, the survival was better than could have been expected either for stage III endometrial carcinoma, or stage II ovarian carcinoma. This supports the view that many of those tumors should be considered independent stage I carcinomas. Another fact in favour of this hypothesis is the strong correlation between myometrial invasion and prognosis in these cases, which is comparable to that found in endometrial carcinoma alone.

42 patients with advanced epithelial ovarian carcinoma who were clinically free of disease after completed postoperative chemotherapy were submitted to second-look laparotomy at the University clinics of Bilbao and Santander, in Northern Spain, between 1980 and 1987. Tumor was demonstrated in 22 of the cases (52.3%). This paper deals with the question of whether this knowledge and the ensuing change in therapy resulted in a longterm benefit for the patients or not. In our experience, this was not the case. All second-look-positive patients either died during the follow-up period, or showed tumor progression if they survived more than 6 months. Survival sank to 50% after only 24 months, and steadily thereafter to 0% after 78 months. The therapeutical value of second-look laparotomy is heavily questioned by these results.

A case of 46,XY gonadal dysgenesis with a type III Teter's gonocytoma occurred in the left ovary of a 22-year-old woman. Hormonal, genetic and laparoscopic studies were performed before the diagnosis of gonadal dysgenesis was made. Gonadal neoplasm was found after bilateral gonadectomy.