J. Bouma

ENDODERMAL SINUS TUMOR OF THE OVARY DURING PREGNANCY - A CASE-REPORT

Serum alpha-fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24-year-old female in week 17 of pregnancy. After surgery, chemotherapy was postponed. In week 28 levels of serum alpha-fetoprotein increased, but delivery was delayed until 33 weeks gestation. After delivery, the patient received four chemotherapy courses (cisplatin, etoposide, and bleomycin). Mother (24 months after last chemotherapy) and child are doing well.

Significance of serum SCC antigen as a tumor marker in patients with squamous cell carcinoma of the vulva

The significance of serum SCC antigen as a tumor marker was investigated in 94 women with squamous cell carcinoma of the vulva. The incidence of elevated serum SCC levels varied from 10% in FIGO stage I to 40% in FIGO stage IV. We did not observe a correlation between elevated pretreatment SCC values and the presence of lymph node metastases. During follow-up, elevated serum SCC values were observed in 8 of 19 patients (42%) with recurrent or progressive disease. It is concluded that the determination of serum SCC levels does not provide additional information in the staging of squamous cell vulvar carcinoma, but can be useful for the early detection of recurrent disease during follow-up in some patients. However, elevated serum SCC levels were also found in 25% of patients without demonstrable tumor activity during follow-up and benign skin disorders were recognized as a cause of false-positive SCC results.

Squamous cell carcinoma of the vagina: a report of 32 cases

Between 1982 and 1992, 32 patients with squamous cell vaginal cancer were treated. Fourteen patients had stage I, 11 stage II, two stage III and five stage IV disease. The mean age of stage I and II patients was 64, of stage III and IV patients 73. Six patients were pessary-bearing, two had a total procidentia, eight had been treated for cervical intraepithelial neoplasia (CIN), one for cervical cancer and one for vulvar cancer 5–21 years before diagnosis. One patient had had external irradiation for endometrial cancer 15 years before. Nine patients had no follow-up examinations after treatment for CIN, for vulvar cancer or after insertion of a pessary. In 14 patients doctors or patients delays were considerable. Most patients presented with vaginal discharge or bleeding, and urinary symptoms. Various treatment modalities were used. The selected patients who could be treated by surgery did best. Only patients with a stage I tumor or a stage II tumor with a diameter of at most 30 mm survived. Tumor stage and tumor diameter were the important prognostic factors. No patient died of disease after 33 months. Failure in obtaining local control was the usual cause of death. Recommendations for prevention or early diagnosis are formulated.

Zeniplatin in Patients with Advanced Ovarian Cancer, a Phase II Study with a Third Generation Platinum Complex

25 patients with residual or recurrent ovarian cancer were treated with the new platinum complex zeniplatin (CL 286,558) and 23 patients were evaluable for response. Responses were achieved in 4 patients, 1 complete and 3 partial remissions (16%). 7 patients had stable disease and 12 patients had tumour progression. At a median follow-up of 12 months, the median progression-free survival in responding patients was 11 months and overall survival 81%. The median overall survival of progressive patients amounted to 9 months, indicating the advanced stage of disease in most patients. Renal function was monitored by isotope clearance studies. There was no significant change in effective renal plasma flow (ERPF) or glomerular filtration rate (GFR) in 10 patients who completed six cycles of treatment. 1 patient with a marginal creatinine clearance at baseline suffered from sudden and severe renal failure during the first cycle. Zeniplatin may be active in relapsing, platinum-pretreated patients, and has no direct effects on renal function as measured by isotope clearance. Despite these findings, occasional nephrotoxicity may occur in patients with compromised kidney function, even with prophylactic hydration, and thus limit the application of this new analogue.

Inhibin as a marker for granulosa-cell tumors

In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo-oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow-up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.

A phase I-II study with intraperitoneal cisplatin plus systemic etoposide in patients with minimal residual ovarian cancer

In patients with residual ovarian cancer after standard platinum-based induction, dose intensification was achieved by intraperitoneal administration of cisplatin 90 mg/m2 with intravenous Na thiosulphate and increasing dosages of etoposide. 40 patients entered the study, 4 on 200 mg/m2, 6 on 400 mg/m2, 22 on 600 mg/m2 and 8 on 800 mg/m2 etoposide. The optimal dose for etoposide was 600 mg/m2. 29 patients on the two highest dose steps were evaluable for response. 14 patients reached a complete remission, which was surgically confirmed in 6. All these patients initially had tumour residuals smaller than 1 cm. 3 patients had a partial response, 4 had stable disease and 8 progressed. At a maximal follow-up of 2 years (median 12 months), median time to progression was 12 months and median overall survival was 14 months. Of the 14 patients with complete remission, 2 relapsed at 9 and 11 months. Apart from a rash, in 4 of 22 patients at 600 mg/m2 and in 5 of 8 at 800 mg/m2 etoposide, the main toxicity was leukopenia grade 3-4 in 58% of cycles on 600 and in 76% at 800 mg/m2 etoposide. Leukopenic fever, however, occurred only three times; thrombocytopenia was rare. Cycles had to be delayed sporadically and the etoposide dose was reduced in 9% of all cycles at 600 and in 11% at 800 mg/m2. Intraperitoneal instillation of cisplatin gave no peritoneal symptoms. Intraperitoneal cisplatin with intravenous etoposide was tolerable and effective for patients with small tumour residuals after induction for stage III ovarian cancer.

CA 125 in tumor tissues, cyst fluids, cervical mucus and serum

Ce l l u l a r p r o l i f e r a t i o n i s potent ly st imulated by a fami ly of hormonally act ive polypept ides, the growth fac tors . Growth f_actors have the po ten t ia l to induce c e l l u l a r t ranstormat ion i f they act at the wrong time or in the wrong place. Factors inducing c e l l t ransformat ion have been shown to be a r e l a t i v e to epidermal growth fac to r (EGF) and in te rac t with c e l l u ] a r receptors .f_or EGF (EGF Like f ac to r s ) , lhe aim o• t h i s study was to inves t iga te ovarian carcinomas f o r the presence o• EGF l i k e fac to rs (EGF-F) in co r re la t i on to c l i n i c a l parameters. Specimens of ovarian carcinomas and nonmalignant t i ssues were ext rac ted with 1 M acet ic acid, centri• end the supernmten ts analyzed • the presence o• EGF F by a EGF radio receptorassay, lhe ~actor content i s expressed as EGF competing a c t i v i t y in n~ EGF units/mg pro te in . In ex t rac ts of nonmalignant t i ssues, i . e . normal ovar ies and myometrJum, and ovarian carcinomas EGF-F could be detected. However, the fac to r contents o f the d i f f e r e n t ex t rac ts var ied w ide l y . . I n nonmalignant t issues fac to r leve ls did not exceed 6 ng EGF units/mg. 18/42 ovarian carcinomas contained high fac to r concentrat ion between 6-17 EGF units/mg. Pat ients were separated in two groups with low (<6 ng) and high (>6 n~) EGF-F t i ssue leve ls . Both groups were cor re la ted with c l i n i c a l date. No d i f fe rences were noticed to h i s t o l o g i c a l subtype and steroidhormonereceptorstatus. Low res idua l tumorrest (< 2 cm) a f t e r primary surgery was found in 11/20 cases with low • content compared to 4/15 cases with high • content. The responserate to a c is-p lat inum combinat ion chemotherapy in the group with low fac to r concent r a t i o n was: 4/21 progressive disease (PD) 3/21 no change (n.c. ) and 14/21 remission (CR+PR). The resu l t s in the group with high fac to r concentrat ion were: 9/24 PD, 5/14 n.c. and 0/14 CR+PR. Dit• in the su rv i va l t ime of both groups were also not iced. However, the case number is too low f o r de ta i led s t a t i s t i c a l analysis, lhese results let assume that the bioIooicaI be havieur of ovarian carcinomas couId be influenced by its content of EGF like grovrch factors.