Naohiko Umesaki

Phase II Study of Irinotecan and Cisplatin as First-Line Chemotherapy in Advanced or Recurrent Cervical Cancer

Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m2) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m2 i.v.) on day 1 over 90 min. The patients’ median age was 57 years (range 35–75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41–74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16–62 days). The median survival was 27.7+ months (range, 6.4–52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.

Correlation between the growth of uterine leiomyomata and estrogen and progesterone receptor content in needle biopsy specimens

OBJECTIVE To examine the relationship between estrogen receptor (ER) and progesterone receptor (PR) content in needle biopsy specimens and the growth of uterine leiomyomata after biopsy. DESIGN Prospective clinical study. SETTING University teaching hospital. PATIENT(S) Thirty-one women with uterine leiomyomata and a normal menstrual cycle. INTERVENTION(S) Transcervical needle biopsy of uterine leiomyomata. MAIN OUTCOME MEASURE(S) The relationships between histologic features (smooth muscle content, immunohistochemical expression of ER and PR) and the percent increase over a 12-month observation period in the volume of the largest myoma nodule measured by magnetic resonance imaging were analyzed. RESULT(S) Both the density and intensity of immunohistochemical staining of PRs in uterine leiomyoma tissue showed significant positive correlation with leiomyoma growth. CONCLUSION(S) The growth of uterine leiomyomata can be determined by histologic and immunohistochemical analysis of needle biopsy specimens from uterine leiomyomata.

Neonatal thrombocytopenia induced by maternal anti-HLA antibodies: a potential side effect of allogenic leukocyte immunization for unexplained recurrent aborters

Allogenic leukocyte immunization is one of several treatments tried for unexplained recurrent aborters, and is reported to have few maternal and neonatal side effects after the immunotherapy having been reported to date. In the present study, we report a rare case of neonatal thrombocytopenia (41000 cells/microl) observed in a female infant delivered by an unexplained habitual aborter. The mother was immunized with her husbands leukocytes once before pregnancy and twice at the 5th and 6th week of her successful pregnancy. Serological studies using mixed passive hemagglutination assays (MPHA) showed that maternal serum did not contain any antibodies which were reactive to 11 platelet-specific antigens, or to granulocyte antigens extracted from 9 persons. Lymphocyte cytotoxicity tests, however, showed that maternal serum but not infant serum had anti-HLA antibodies against both paternal and infant lymphocytes. Moreover, the maternal serum was found to have anti-HLA IgGs against platelet antigens extracted from the father and the infant. It is highly likely that this case of neonatal thrombocytopenia was caused by transplacental perfusion of maternal anti-HLA antibodies whose production was induced or enhanced by the allogenic leukocytes immunizations.

Successful preoperative diagnosis of massive ovarian edema aided by comparative imaging study using magnetic resonance and ultrasound.

Massive ovarian edema (MOE) is a rare disease. Therefore, preoperative diagnostic method of massive ovarian edema (MOE) has not been established. We have succeeded in making a preoperative diagnosis of MOE aided by ultrasonogram and magnetic resonance imaging (MRI) and the patients ovaries were preserved. Characteristics and proposed diagnostic imaging criteria for MOE are discussed.

Danazol Suspension Injected into the Uterine Cervix of Patients with Adenomyosis and Myoma

We investigated the effect of local injections of danazol suspension (DZS) into the uterine cervix. In the cervix, danazol (DZ) reached high concentrations 1 and 4-6 h after injection; then it decreased. In the endometrium, the DZ level reached a peak 1 h after injection, and then declined. On the other hand, the DZ concentration tended to increase with time after injection in ovarian tissue and it remained at a relatively constant level for more than 2 days. During treatment with DZS, various subjective symptoms and clinical findings gradually improved from the 4th week after the start of injection onward. Moreover, an improvement of subjective symptoms was observed in all the patients by the 24th week.

Correlation between shrinkage of uterine leiomyoma treated with buserelin acetate and histopathologic findings of biopsy specimen before treatment

OBJECTIVE To analyze histopathologic features related to myoma volume reduction after treatment with a GnRH agonist, buserelin acetate, in needle biopsy specimens obtained before treatment. DESIGN Prospective clinical study. SETTING University teaching hospital. PATIENT(S) Twenty women with normal menstrual cycles and symptomatic uterine myomas. INTERVENTION(S) Buserelin acetate was administered intranasally (900 micrograms/d) for at least 16 weeks; transcervical needle biopsy of the uterine myoma was done before this treatment. MAIN OUTCOME MEASURE(S) The relation between histopathologic features (degree of cellularity, hyaline change, and collagen content) and the percent decrease in the volume of the largest myoma at 16 weeks measured by magnetic resonance imaging. RESULT(S) The correlation between the degree of hyaline change and the percent decrease in the myoma volume was significant, as was that with the proportion of collagenous tissue in the specimens. CONCLUSION(S) We predicted myoma volume reduction after treatment with a GnRH agonist by histologic analysis of the uterine leiomyoma before treatment.

Increased Natural Killer Cell Activities in Patients Treated with Gonadotropin Releasing Hormone Agonist

Natural killer (NK) cell activity in patients treated with gonadotropin-releasing hormone agonists (GnRH-a) was studied. The subjects were 8 patients with endometriosis (6 with ovarian endometrial cyst, 2 with adenomyosis) and 3 patients with uterine leiomyoma. Changes in serum estradiol (E2) concentration and NK cell activity in peripheral blood were analyzed before and after GnRH-a treatment (buserelin 900 μg/day for 4–5 months). NK cell activity was determined by 51Cr release assay and E2 by radioimmunoassay. NK cell activity before GnRH-a treatment was 37.7 ± 19.0%, and after therapy activity increased significantly to 50.8 ± 18.2%. However, no significant correlation between the increase in NK cell activity and the decrease in E2 concentration was found. Results indicate that the standard GnRH-a treatment for endometriosis and uterine leiomyoma might increase NK cell activity. The etiology of the increase of NK activity with GnRH-a treatment is likely related to factors other than E2 concentration.

Production and physiological function of granulocyte colony-stimulating factor in non-pregnant human endometrial stromal cells

Effects of granulocyte colony-stimulating factor (G-CSF) on proliferation and differentiation of normal human endometrial stromal cells were investigated in an in vitro decidualization culture of stromal cells. Unstimulated stromal cells secreted little prolactin and G-CSF, whereas 8-Br-cAMP-stimulated stromal cells secreted higher levels. There was no relationship, however, between the levels of prolactin and G-CSF secreted from the stimulated cells. Detectable levels of prolactin secretion were not found in two of six stromal cell cultures stimulated with 8-Br-cAMP; however, these two culture supernatants contained high concentrations of G-CSF. Co-stimulation of the stromal cells with 8-Br-cAMP and G-CSF enhanced prolactin secretion from the stimulated cells in a G-CSF concentration-dependent manner without any change in viable cell numbers. However, G-CSF did not affect prolactin secretion or viable cell numbers of 8-Br-cAMP-stimulated decidualized cells. These results indicate that G-CSF enhances cAMP-mediated decidualization of human endometrial stromal cells in an autocrine or paracrine fashion.

Plasma Granulocyte Colony Stimulating Factor Concentrations in Pregnant Women

We measured the plasma granulocyte colony stimulating factor (G-CSF) concentrations in pregnant women to evaluate the association between G-CSF and increased neutrophil counts that has been observed during pregnancy. We examined 96 pregnant and 10 nonpregnant women. The G-CSF concentrations were assayed using a sandwich enzyme immunoassay. The G-CSF concentrations in pregnant women were significantly higher at all times than those of nonpregnant women. The G-CSF concentrations were also significantly higher during than before labor. The plasma G-CSF concentrations were positively correlated with the neutrophil counts during the 3rd trimester only. In conclusion, increased G-CSF concentrations may be related to the increases in neutrophil counts in pregnant women, especially during the 3rd trimester.

Preoperative diagnosis of a rudimentary uterine horn

Two cases of rudimentary uterine horn were able to be diagnosed prior to operation. The case of rudimentary horn with cavity non-communicating to unicornuate uterus was easy to diagnose. Transabdominal ultrasonography and computed tomography (CT) demonstrated the uterus to have binodular structure and two uterine lumina. However, the case with pregnancy was difficult to diagnose. In this case, thick myometrium could be seen by ultrasonography to enclose the sac. In both cases hysterosalpingography revealed unicornuate uterus.