Juhani Mäenpää

Endometrial stromal sarcoma: A report of nine cases

Nine cases of endometrial stromal sarcoma are described. Four of the patients were categorized as having a uterine endolymphatic stromal myosis (ESM) with less than 10 mitoses per 10 HPF and five patients as having an endometrial stromal sarcoma (ESS) with more than 10 mitoses per 10 HPF. Another prognostic distinction based on the degree of stromal differentiation is also discussed. The symptomatology, diagnostic means, clinical features, and treatment are described.

Chemosensitizing effect of an antiestrogen, toremifene on ovarian cancer

Abstract The chemosensitizing effect of an antiestrogen, toremifene, was studied on 2 human ovarian cancer cell lines in vitro and on 3 fresh surgical ovarian tumor expiants with the aid of the subrenal capsule assay (SRCA). Also, 11 patients with secondarily drug resistant, recurrent gynecologic cancer (8 ovarian and 3 uterine cancers) were treated with 240 mg toremifene daily for 1 week before each course of cytostatics. Toremifene potentiated the effect of doxorubicin on both cell lines. This was also the case on 1 cell line that was not completely resistant to doxorubicin. The SRCA showed a clear potentiating effect of toremifene only on the tumor overtly resistant to the combination of cisplatin, doxorubicin, and cyclophosphamide. Of the 11 patients treated with toremifene and cytostatics, the response of 8 patients was evaluable: 3 had partial response, 3 no change, and 2 progressive disease. Toremifene seems to have a chemopotentiating effect on gynecologic drug-resistant tumors.

Malignant pericardial effusion in ovarian carcinoma cured by systemic chemotherapy

A case of malignant pericardial effusion in a 67-year-old patient with serous ovarian cystadenocarcinoma is presented. Pericardial effusion was treated successfully with cyclophosphamide, doxorubicin, and cisplatin. The primary tumor had previously been assumed to be sensitive to this combination by using an in vivo predictive test, the subrenal capsule assay.

Luteal function declines after laparoscopic sterilization by Hulka or Filshie clips.

We evaluated the influence of laparoscopic sterilization by Hulka or Fishie clips on corpus luteum function. Changes in corpus luteum function were evaluated in 46 women, before and after sterilization by Hulka (n = 22) or Filshie clips (n = 24). The mean age of the participants was 37 years (range 31-43 years). All women were healthy with regular menstrual cycles. Serum progesterone (P) was measured in one cycle before, and 3 and 12 months after the sterilization on cycle day 20-24. Endometrial biopsies were performed in the luteal phase before and one year after the procedure. The women measured the basal body temperature daily and kept a menstrual diary. The luteal phase P concentrations declined after the sterilization and the values were at the lowest level 3 months after the procedure (27.9 +/- 14.3 nmol/L vs. 18.7 +/- 13.4 nmol/L, = 0.0016). The values seemed to have recovered by 12 months (23.0 +/- 14.0 nmol/L, = 0.114 vs. baseline). Endometrium tended to be out-of-phase more frequently 1 year after the sterilization than before the surgery (= 0.065). Laparoscopic tubal sterilization is associated with an increased risk of luteal phase deficiency. However, the change may be only temporary in nature.

Chemosensitizing effect of an antiestrogen, toremifene, on ovarian cancer

The chemosensitizing effect of an antiestrogen, toremifene, was studied on 2 human ovarian cancer cell lines in vitro and on 3 fresh surgical ovarian tumor explants with the aid of the subrenal capsule assay (SRCA). Also, 11 patients with secondarily drug resistant, recurrent gynecologic cancer (8 ovarian and 3 uterine cancers) were treated with 240 mg toremifene daily for 1 week before each course of cytostatics. Toremifene potentiated the effect of doxorubicin on both cell lines. This was also the case on 1 cell line that was not completely resistant to doxorubicin. The SRCA showed a clear potentiating effect of toremifene only on the tumor overtly resistant to the combination of cisplatin, doxorubicin, and cyclophosphamide. Of the 11 patients treated with toremifene and cytostatics, the response of 8 patients was evaluable: 3 had partial response, 3 no change, and 2 progressive disease. Toremifene seems to have a chemopotentiating effect on gynecologic drug-resistant tumors.

Serum total renin after tubal sterilization.

Abstract The effect of laparoscopic tubal sterilization by Hulka or Filshie clips on serum total renin levels was evaluated in 33 healthy, regularly menstruating women. Serum total renin levels were measured in the follicular (days 3 to 7) and in the luteal (days 20 to 24) phase during the cycle immediately preceeding the sterilization and 12 months after the procedure. The total renin secreted did not change after the sterilization. The follicular phase levels were lower (160 ± 113 and 170 ± 93 ng/l, respectively) than luteal phase levels (230 ± 124 and 228 ± 83 ng/l, respectively) in both cycles studied (p=0.0001 for both). The length of the menstrual cycle was not affected, either. Laparoscopic tubal sterilization caused no measurable changes in total renin secretion during one year follow-up.

Establishment and characterization of UM-EC-2, a tamoxifen-sensitive, estrogen receptor-negative human endometrial carcinoma cell line

UM-EC-2 was established from a patient with poorly differentiated stage IB endometrial carcinoma. This cell line produces tumors in nude mice that have the same histological features as the patients tumor. UM-EC-2 cells express b2-microglobulin, the epidermal growth factor receptor (EGF), and the H blood group antigen. This membrane antigen phenotype is consistent with cells of human endometrial origin. The karyotype of UM-EC-2 is fairly complex, with rearrangements affecting all chromosomes except 3, 10, 14, 19, and 20. There were two populations of cells, a hyperdiploid population with a modal number of 53-55 and a hypertetraploid population with a modal number of 109. A postulated sequence of events before and after tetraploidization is suggested based on the number of copies of individual chromosomes and rearrangements. Comparison of the UM-EC-2 karyotype to that of UM-EC-1 (a previously described line from a different patient with endometrial carcinoma) revealed that the two lines share eight very similar chromosome changes, which include loss of most of chromosome 4, breakpoints affecting proximal bands on 8p, loss of most of 9q, a breakpoint at 12q22, loss of 13q, breakpoints in proximal bands on 18q, and a breakpoint at 22p11. These changes may represent nonrandom chromosome abnormalities in poorly differentiated endometrial cancer. Estrogen (ER) and progesterone (PgR) receptors were not detected in either the primary tumor or the cell line. Nevertheless, UM-EC-2 cells were very sensitive to growth inhibition by tamoxifen (TAM) in vitro. One micromolar TAM caused 50% inhibition of cell growth, 2.5 microM caused cytostasis, and 5 microM TAM was cytotoxic, killing all cells after 5-7 days of exposure to the drug. Paradoxically, 100 nM estradiol (E2) caused a moderate increase in the growth of the cells but it did not prevent or reverse growth inhibitory effects of TAM. These findings support the concept that in some tumors TAM causes growth inhibition by an ER-independent mechanism. UM-EC-2 cells were also sensitive to growth regulation by EGF. Thus, these cells provide a new in vitro model of human endometrial cancer in which the roles of both TAM and EGF as growth regulatory substances can be investigated.

Response of ovarian cancer to combined cytotoxic agents in the subrenal capsule assay: Part I

The subrenal capsule assay in normal immunocompetent mice was used to test the responsiveness of ovarian cancer to combination chemotherapy. Of the assays, 42 were of untreated tumors and 19 of previously treated tumors. Fiftynine (9%) of the assays were evaluable. The previously treated tumors were less sensitive than the untreated ones. Of the treated tumors 44% were sensitive, 33% intermediately sensitive, and 22% resistant versus 56, 44, and 0%, respectively, of the untreated tumors (P < .01). Repeat assays for the tumors of seven patients were performed successfully after five to eight courses of therapy with the combination of doxorubicin, cyclophosphamide, and cisplatin. The responsiveness to this combination had weakened significantly (P < .01); the response of only one tumor remained unchanged. The fates of resistance to the drug combinations doxorubicin-cyclophosphamide-cisplatin, doxorubicin-cyclophosphamide-tegafur, and cyclophosphamide- vincristine were 11, 10 and 21%, respectively; there was, however, considerable interindividual variation in tumor responses td these combinations. Of other combinations, hexamethylmelamine combined with 4-epidoxorubicin, aclarubicin, or chlorambucil and cisplatin had effect, whereas the combinations of cisplatin and etoposide and of tegafur and methotrexate or mitomycin were quite ineffective, as measured by the assay. The reliability of the subrenal capsule assay in normal immunocompetent mice is discussed, and it is concluded that the assay can be used to assess the response of ovarian cancer to chemotherapy, including multidrug therapy, without routine histologic control.