[Effects of long-term administration of tamoxifen on vaginal epithelium and complications of endometrial lesions in breast cancer patients].

The effects of tamoxifen (TAM) on 56 postoperative breast cancer patients who were orally administered TAM and followed up at Cancer Institute Hospital from 1989 to 1992 were studied retrospectively. The maturation index (MI) and karyopyknotic index (KPI) were employed to investigate the effects of TAM on vaginal epithelial cells cytologically, and the patients were also monitored for complications. The results were as follows. (1) The relationship between the duration of TAM therapy and the changes in MI and KPI were analyzed. It was found that, for the MI, intermediate cells (IMT) increased and superficial cells (ST) decreased during TAM administration for up to 4 years, but when the TAM therapy was continued for longer than 4 years, IMT showed a gradual decrease and ST increased gradually. The KPI values showed similar changes. (2) Studies of the endometrium (26 cases) revealed a tendency for few of the long-term administration cases to show a picture of atrophy. Of the total of 56 patients, endometrial lesions were observed in five cases (8.9%), consisting of endometrial cancer in three and cystic glandular hyperplasia in two. The mean duration of TAM administration to these five patients was 54 (+/- S.D.26.8) months. These data indicate that long-term oral administration of TAM involves the possibility of having an estrogenic effect on the vaginal epithelium and the uterine endometrium.

[Comparison between old and new FIGO staging of endometrial carcinoma--the significance of positive peritoneal cytology].

Three hundred fifty-two patients with endometrial adenocarcinoma who underwent primary surgical therapy between 1984 and 1991 were evaluated. (1) Eighty-three (23.6%) had positive peritoneal cytology (PPC). (2) The cumulative 5-year survival rates (5-y. survival rate) for the former clinical stages were 88.8%, 86.1%, 52.9% and 0% for stages I-IV, respectively, showing a significant difference between stage III and IV (p < 0.05). The new clinical stage 5-5. survival rates were 97.5%, 100%, 69.9% and 25.9% for stages I-IV, respectively. There was no significant difference between stages I and II, but there were significant differences between stages I.II and III (p < 0.001) and between stages III and IV (p < 0.05). (3) In cases of new stage III, 5-y. survival rates for stage IIIA and IIIB.C were 83.7% and 33.6%, respectively (p < 0.01). Those for stage IIIA with PPC were very good in comparison with stage IIIA cases with other factors (90.3% vs 49.2%; p < 0.05). When the patients in stage IIIA with only PPC were separated into 2 groups, i.e., a myometrial invasion less than 1/2 and no cervical involvement group and a myometrial invasion greater than 1/2 or/and cervical involvement group, their 5-y. survival rates were 97.2% and 75.1% respectively (p < 0.05). (4) Recurrence developed in 15.3% of patients in stage IIIA with only PPC, and in 64.7% of patients in stage IIIA with other factors (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Characteristic of cystic glandular hyperplasia as a precursor of endometrial carcinoma].

The natural history and biological behavior of cystic glandular hyperplasia (CGH), which has been considered to be a precursor of endometrial carcinoma, still remain unclear. The present prospective study included 52 patients with CGH, who were followed up for 6 months to 5 years with occasional curettage, surgical procedures or hormonal therapy. The lesion disappeared in 35 cases (67.3%), persisted in 12 cases (23.1%) and became more serious in 5 cases (9.6%). Of these 5 cases, one case was found to have endometrial carcinoma during her follow-up. Nuclear DNA analysis was performed by Flow cytometry in 8 CGH cases. Eighty four point nine % of the cells from these 8 cases were in G0+1 phase, 8.3% in S phase and 7.4% in G2 + M phase. The proliferation index for CGH was 15.7%. Proliferative and mitotic activities of CGH were found to be similar to those of adenomatous hyperplasia, and the levels of these activities were between those of normal endometrium and atypical hyperplasia.G1.

[Prognostic factors of endocervical type adenocarcinoma in uterine cervix].

Adenocarcinoma of the uterine cervix accounts for an increasing percentage of cervical cancers with controversial clinical problems. Three hundred and thirty-seven cases of endocervical type, adenocarcinoma cases were treated at the Cancer Institute Hospital between 1950 and 1984. Of the many clinicopathologic variables evaluated for prognosis, the following were significant. (1) Clinical Stage: Five and 10 year survival in each stage was: 83.3% and 78.0% (stage I), 71.6% and 55.8% (stage II) and 27.1% and 19.7% (stage III), respectively (p < 0.01, < 0.05). (2) Myometrial invasion: One hundred and forty stage Ib.II patients were operated on and then separated into 3 groups according to the degree of myometrial invasion. Five and 10 year survival in the "< 1/3" group was 92.7% and 86.9%, the "1/3-2/3" group 86.6% and 82.3% and the "> 2/3" group 75.0% and 63.2%, respectively. There was a significant difference between the "< 1/3" and "1/3-2/3" groups and the "> 2/3" group (p < 0.05). (3) Pelvic lymph node metastasis: Five and 10 year survival in negative cases of pelvic lymph node metastasis was 90.7% and 85.8%, compared with 40.9% and 29.8% in positive cases (p < 0.05). (4) Cardinal invasion: Minimal 5 year survival for negative cases was 71.2%, compared with 11.1% for positive cases (p < 0.001). (5) Surgical therapy for early stage cancer: Minimal 5 year survival for operated cases was 81.3%, compared with 58.5% for irradiated cases (p < 0.01).

[Treatment of advanced or recurrent cervical cancer by a new BOMP regimen consisting of bleomycin, vincristine, mitomycin-C, and low-dose consecutive cisplatin].

Twenty-five patients with cervical cancer (4 post-operative cases with FIGO stage Ib or IIb, 2 with stage IV, and 19 recurrence) were treated with a new BOMP consisting of bleomycin (5 mg/body, drip, i.v., days 1-7), vincristine (0.7 mg/m2, bolus, i.v., day 7), mitomycin-5 (7 mg/m2, bolus, i.v., day 7) and cisplatin (10 mg/m2, drip, i.v., days 1-7). The mean age of the patients was 54 years (range 30-77). Prior therapy included radiotherapy (13 cases), radical hysterectomy (11), and none (1). Fifteen (79%) of the 19 evaluable patients responded, including 6 with a complete response (CR) lasting over 15 months. Almost all the disease located in lung, liver, bone, and vulva showed a response. In particular, lesions confined to the lung had a 100% CR when the size of each tumor was under 2 cm in diameter even in the case of multiple metastasis. In contrast, 9 patients with pelvic disease had a 56% response with only 1 CR who had no previous radiotherapy. Such a poor response in the pelvic disease was considered to be due to vascularity reduced by prior radiotherapy. The important factors affecting the response to a new BOMP were found to be lesion size, prior radiotherapy, and the site of lesion. Patient age, performance status (PS), and the interval from a previous treatment to BOMP were not of significance with regard to response. The dose limiting factor was hematologic toxicities. Other toxicities including nausea, renal dysfunction, pulmonary fibrosis, and loss of hair were acceptable. Thus, the decrease in the PS of patients due to BOMP was minimal. It is suggested that this regimen will be useful as a neoadjuvant chemotherapy for advanced cervical cancer.

[Evaluation of UFT administration in patients with ovarian cancer who had no evidence of disease after the initial therapy].

Twenty nine patients with ovarian cancer of common epitherial origin who had no evidence of disease proved by computed tomography after the initial operation and chemotherapy were studied. The patients were randomized into two groups; (A) administration of UFT (1-(2-tetrahydrofuryl)-5-fluorouracil mixed with uracil) orally at a daily dose of 300 mg, 12 cases, (B) no further therapy, 17 cases. The therapeutic efficacy of UFT was assessed pathologically at the second look laparotomy (SLL). Plasma levels of 5-FU, tegafur and uracil were determined once a month to check whether patients intake UFT regularly or not. There were no significant difference in the mean age, in the distribution of numbers of patients in FIGO stage and histological cell type, in the mean total doses of CDDP and doxorubicin given at the initial chemotherapy [CDDP: (A) 352 +/- 152 mg, (B) 464 +/- 192 mg, doxorubicin: (A) 118 +/- 76 mg, (B) 119 +/- 92 mg] and in the duration between the initial operation and the SLL [(A) 484 +/- 154 days, (B) 414 +/- 274 days] between the two groups. The mean periods in the administration of UFT were 484.3 +/- 154 days. Recurrence was identified at the SLL in 1 case (8.3%) at paraaortic lymph nodes in (A) and 3 cases (17.6%) at the mesenterium, cul-de-sac and ascitic fluids in (B). No significant difference of recurrence ratio was observed between the two. Further long-term observation is required to assess the advantage of administration of UFT.

[Antigenic phenotype of the lymphocytic component of regional lymph nodes in patients with cervical cancer and its modulation by lentinan].

Immunohistochemical study with various monoclonal antibodies to the mononuclear cell surface antigens was carried out on the regional lymph nodes in patients with cervical cancer to assess the augmentative effect of lentinan. Zero, 2, 4, or 6 mg of lentinan was administered i.v. one day prior to surgery to patients with cervical cancer (14 cases with FIGO stage 0 and 19 with FIGO stage Ib) and those with benign gynecologic tumors (8 cases with myoma uteri and 6 with ovarian tumor). Frozen sections of fresh pelvic lymph nodes obtained from these patients during surgery were stained by the ABC (avidin-biotin-peroxidase complex) method using several monoclonal antibodies to define the surface phenotype of mononuclear cells. The results were as follows: 1. Pelvic lymph nodes in patients with benign disease: In the absence of lentinan, lymphocytes stained with Leu 3a antibody were more numerous than those stained with Leu 2a, and both were observed mainly in the paracortical area (PC). The number of lymphocytes stained with Leu 4 antibody was practically equal to the sum of those stained with Leu 3a and Leu 2a. HLA-Dr positive lymphocytes were present in moderate numbers in PC and sinus. The above findings were not changed by the administration of lentinan. Cells stained with monoclonal antibodies including Leu 7, 11, M3, and IL-2 receptor (IL-2R) were very few or absent. 2. Pelvic lymph nodes in patients with cervical cancer receiving no lentinan: The findings obtained in these cases were much the same as those in patients with benign tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical study of the vulvar Paget's disease: report of 8 cases].

Between 1949 and 1987, 8 cases of the vulvar Paget's disease were treated at the Cancer Institute Hospital. These cases constituted 9.5% of the total number of the vulvar malignancies at our hospital during the same period. The clinicopathological findings were described. The average age was 73.3 years. The most frequent symptom was vulvar eczematous change with itching, which was seen in 7 cases (87.5%). About 5 years was required from onset of the disease until diagnosis. Vulvar cytologic examination revealed positive for cancer in 5 out of 8 cases (62.5%). One patient developed squamous cell carcinoma of the face. All patients underwent operation. Two patients had preoperative adjuvant chemotherapy by Bleomycin which was not effective histologically. Five patients had a underlying invasive tumor (62.5%) at initial therapy. The 5-year survival rate was 50.0%. Prognosis of the vulvar Paget's disease appears to be poor.

[CDDP-ACR treatment in patients with recurrent ovarian cancer with prior chemotherapy containing CDDP--a preliminary study of a 14-day continuous infusion of CDDP with ACR].

Six patients with recurrent ovarian cancer who had prior chemotherapy were studied for the clinical efficacy of CDDP-ACR treatment. Five out of the 6 had received CDDP a total doses of 1,320, 780, 750, 475, and 340 mg. CDDP-ACR therapy consisted of continuous infusion of CDDP at a daily dose of 10 mg/m2 over 14 days (total CDDP doses; 140 mg/m2) and of intermittent infusion of ACR (aclarubicin) at a dose of 20 mg/body every other day (total ACR doses: 140 mg). There were one CR and five PR and a response rate up to 100% was noted. Toxicity was manifested in slight nausea or vomiting, but there was no nephrotoxicity. However bone marrow was severe. Thrombocytopenia less than 50,000/mcl in 4 pts (67%) and leukopenia less than 1,000 mcl in 3 pts (50%). The mean filterable platinum exposure measured by area under the concentration-time curve (AUC) was as high as 19.7 +/- 6/0 mg.hr/ml. In conclusion the bone marrow toxicity in this regimen was severe, but the therapeutic efficacy was promising. Further studies on the appropriate infusion time and the minimum effective dose of CDDP are needed.

A nuclear DNA study of uterine cervical dysplasia with reference to its prognostic significance.

To further define the nuclear DNA content of uterine cervical dysplasia and its relationship to prognosis and epidemiological features, a retrospective study using Papanicolaou stained cytological specimen and TICAS was undertaken. 1. Dysplasia patients was common among young females who had a background of low age first pregnancy, multiple Gravidity-Parity, the complication of inflammation and the use of hormonal contraceptives and progressed rapidly. It is recommended that a test should be repeated within 2 to 3 months regardless of the severity of the dysplasia and patients should be followed up for at least 2.5 to 3 years. 2. The DNA histograms were classified into 3 types (A,B and C): Type C, which had the stem line in an aneuploidy area, showed more severe dysplastic cases. This may be due to the proliferation rate and significant alternation in the chromosomes and mitoses. Nuclear DNA analysis using TICAS and Papanicolaou stained cytological material could discriminate between the progressive group and the persistent or regressive group. In addition, the mean nuclear area might be the best indicator of prognosis in uterine cervical dysplasia.

[Therapeutic results of malignant ovarian tumor].

One hundred and fifty patients with malignant ovarian tumors were treated in the Cancer Institute Hospital between 1949 and 1977. Most (103; 68.7%) of the patients had simple primary ovarian cancer. A retrospective study was performed in these 103 patients to investigate the relationship between the 5-year survival rate and the clinical stage and primary treatment. The 103 patients were classified according to FIGO criteria. The survival rates for stages I, II, III and IV were 73.7%, 50.5%, 17.4% and 0%, respectively. As the primary treatment, operations were performed on 92 of the 103 patients. To conclude, of primary importance in the treatment of ovarian cancer is the surgical, complete as possible removal of the tumors. Postoperatively, radiotherapy and chemotherapy should be used. Recently, second look operations have come into wider use. General procedures for the surgical and postoperative treatment of progressive ovarian cancer have been established. Although surgical procedures for the treatment of early ovarian cancer have also been established, there are no consistent procedures for postoperative treatment. Since the incidence of ovarian cancer is increasing, the development of appropriate methods for early diagnosis and treatment of this carcinoma is eagerly awaited.