Search

A new platinum complex, nedaplatin, has been reported to be effective for both ovarian and cervical cancers. We designated a phase I dose-escalation study of a combination chemotherapy of nedaplatin and cisplatin to investigate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Six patients, including two with advanced cervical cancer, three with ovarian clear cell adenocarcinoma and one with endometrial clear cell adenocarcinoma, were enrolled in this study. The doses of the two agents were escalated alternatively, i.e., a tandem method, from 40 to 80 mg/m2 by 20 mg/m2. Nedaplatin and cisplatin were administrated by intravenous drip infusion and repeated after an interval of at least 4 weeks, as a rule. The major toxicity observed was hematotoxicity. One of the 6 patients dropped out of this study because of severe hematotoxicity after 80 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin were administered. With a dose of 80 mg/m2 nedaplatin and 80 mg/m2 cisplatin, severe neutropenia was found in all 6 patients, and thrombocytopenia and anemia were found in 1 patient, respectively. A slight hearing loss was detected by audiometry in 5 patients, but no one was inconvenienced in daily life. Mild nausea and vomiting were also observed in all 6 patients. In conclusion, the DLT of this combination therapy was hematotoxicity and the MTD was 80 mg/m2 for nedaplatin and 60 mg/m2 for cisplatin, respectively. Thus, 60 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin may be recommended for combined administration.

We evaluated the incidence of synchronous or metachronous multiple primary cancer, hereditary or familial cancer, and the familial aggregation of cancer in 142 patients who were treated for endometrial cancer at Tsukuba University Hospital in the period 1977 to 1995. Synchronous multiple primary cancers were identified in 6 of the 142 patients (4.2%). Eleven patients (7.7%) had a history of extraendometrial cancer. Patients with endometrial cancer had a significantly high incidence of a history of breast cancer. Endometrial cancer was diagnosed in two patients who were screened before menopause. Four patients with endometrial cancer (2.8%) subsequently developed extraendometrial forms of cancer. One patient (0.7%) was considered to have a hereditary form of cancer, and 5 patients (3.5%) had familial forms of cancer. A total of 86 cases of cancer were found among 53 kindred (37.3%). More detailed studies are needed to elucidate the aggregation of cancers in the families of patients with endometrial cancer in Japan. Patients with a history of breast cancer should be screened for the presence of endometrial cancer.

Ninety-five specimens from patients with endometrial carcinoma (82 of endometrial type, 6 of adenoacanthoma, 4 of adenosquamous carcinoma, 3 of atypical endometrial hyperplasia) and 13 with ovarian endometrioid carcinoma were stained immunohistochemically with a rabbit polyclonal antibody prepared against the placental form of the enzyme glutathione S-transferase pi (GST-pi). Histological studies showed that the degree of staining decreased as the tumor lost its differentiation in endometrial carcinoma, but the degree of staining was independent of the differentiation in the case of ovarian endometrioid carcinoma. A comparison between the grade of staining of GST-pi in 82 cases of the endometrial type of endometrial carcinoma and 13 cases of ovarian endometrioid carcinoma revealed a stronger stain for the endometrial carcinoma than for ovarian endometrioid carcinoma (p < 0.01, Mann-Whitney's U test). Therefore, the GST-pi value for endometrial carcinoma was different from that for endometrioid carcinoma. In general, as compared with ovarian endometrioid carcinoma, endometrial carcinoma is considered to be resistant to chemotherapeutic agents. In conclusion, these results suggest that there is an apparent correlation between the GST-pi value and chemoresistance of the tumor.

One hundred and six patients with endometrial cancer were treated at Tsukuba University Hospital between 1983 and 1992. Sixteen patients who underwent complete resection were at high risk for recurrence and were given adjuvant platinum-based, multiagent chemotherapy instead of adjuvant radiotherapy. Eligibility criteria included outer-third myometrial invasion (group 1; n = 5), pelvic lymph node metastasis (group 2; n = 3) or both myometrial invasion and lymph node metastasis (group 3; n = 8). Of these three groups at high risk for recurrence, each patient in groups 1 and 2 developed recurrence and died. In group 3 two patients developed recurrence and one patient has died. There was one treatment death due to neutropenic sepsis in group 3. The recurrence sites in all four patients were local and no distant recurrence was noted. In other words, of 15 patients (excluding one treatment death) at high risk for recurrence, three of 12 patients (25%) with deep myometrial invasion and three of 10 patients (30%) with positive pelvic lymph nodes developed recurrence and died. The other 12 patients (include one patient with recurrence; 100 months) have survived for a long interval (range, 45-131 months). The survival rates for stage I, II, III, and IV are 92.6, 89.5, 60.0%, respectively. Patients with stage I in this study had a better survival than those with stage I in the 1984 annual report of the Japan Society of Obstetrics and Gynecology (p < 0.05). The findings of this prospective clinical trial supported those of the randomized trial comparing adjuvant CAP with radiation therapy.

Specimens from 102 cases of ovarian cancer were stained immunohistochemically with a rabbit polyclonal antibody prepared against the placental form of the enzyme glutathione S-transferase (GST-pi). All 28 cases of mucinous adenocarcinoma, 19 of clear cell carcinoma and 4 of malignant transformed dermoid cysts were stained positively with the GST-pi antibody. These tumors are considered to be resistant to chemotherapeutic agents as compared with other epithelial tumors. With regard to the histological grade, the degree of staining was reduced according to the loss of differentiation. An investigation of the relationship between GST-pi stain and the prognosis of the 50 patients with stage 2,3 or 4, according to the Kaplan-Meier method, revealed that the prognosis improved as the staining decreased. In conclusion, results suggested that immunohistochemical staining of GST-pi is correlated with the chemoresistance of the tumor, and may predict the outcome in patients with ovarian cancer.

Recently, the semiautomated tetrazolium-based MTT colorimetric assay have been used to measure chemosensitivity. We also have been used this assay for 4 ovarian clear cell carcinoma cell lines to investigate the chemosensitivity of this tumor. In this study, several problems have been faced to be solved. In this paper, we pointed out these problems and indicated solutions.

The mechanism of right-sided traumatic diaphragmatic hernia following blunt trauma was examined. In 13 cases of Traumatic diaphragmatic hernia admitted to the Department of Traumatology Osaka University Hospital, 3 cases were on the right. All cases were associated with severe injuries in the chest, abdomen and pelvis. Rib fractures, hemothorax, and liver injury were seen in the same site of the ruptured diaphragm. So it seemed that there were some differences in the force itself caused diaphragmatic rupture between right-sided and left. We reviewed 40 cases of right-sided traumatic diaphragmatic hernia reported in Japan. The following results were obtained. Main force which caused right-sided diaphragmatic rupture was the blunt impact to the right thoracic wall. In the right-sided diaphragmatic hernia, the most frequently herniated organ was the right lobe of the liver and there was high-frequency of G-I tract herniation in delayed types. Herniation of the abdominal organs seemed to be varied as the time passed.