Ken Morimoto

A Phase II Study of S-1 in Patients with Metastatic Breast Cancer : A Japanese Trial by the S-1 Cooperative Study Group, Breast Cancer Working Group

BackgroundS-l is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoro-pyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer.MethodsA non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n = 111) were enrolled, and 108 patients were regarded as eligible. S-l was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times.ResultsAmong the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CRplus PR) of 41.7% (95% confidence interval: CI, 32.3–51.5%). The incidences of toxicity (≧ grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group.ConclusionS-l was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.

Plastic Iodophor Drape during Liver SurgeryOperative Use of the Iodophor-impregnated Adhesive Drape to Prevent Wound Infection during High Risk Surgery

We retrospectively investigated factors associated with wound infection after liver resection for hepatocellular carcinoma (HCC), with special reference to use of a plastic adhesive drape impregnated with iodophor. The subjects were 296 patients undergoing liver resection for HCC. Wound infection was defined as purulent drainage from the superficial incision with or without laboratory confirmation. One or more of the following signs was required: pain or tenderness, localized swelling, or redness or heat. Wound infection developed in 25 patients. Regression analysis indicated that low body mass index (BMI), smoking, long preoperative hospital stay, and nonuse of iodophor drapes were risk factors for wound infection. Wound infection was significantly less likely with the use of iodophor drapes (3.1%) than for surgery without iodophor drapes (12.1%). By multivariate regression analysis, BMI, smoking, and lack of drape use were independent risk factors. Most of the bacteria isolated were skin bacteria, including Staphylococcus aureus and Staphylococcus epidermidis. In conclusion, low BMI, smoking, a long preoperative hospital stay, and the lack of iodophor drape use were risk factors for wound infection after liver resection for HCC. The drapes presumably prevented contamination from the skin during the operation.

Granular cell tumor of the male breast: report of a case.

We treated a 35-year-old male with a granular cell tumor in the right breast. Physical examination revealed a solid, flattened, round 3.2 × 2.5-cm mass with an irregular surface, covering skin fixation and right axillary lymphadenopathy. Mammography revealed a welldemarcated high-density mass with a minimal starburst appearance. Ultrasonography revealed a hypoechoic, nonhomogeneous mass with an acoustic shadow. Several enlarged lymph nodes in the right axilla were removed at the time of breast tumor excision. Histologically, the tumor featured nests of round or polygonal cells with abundant eosinophilic cytoplasmic granules and small round nuclei, and the enlarged lymph nodes in the right axilla exhibited no metastasis. Immunohistochemically, there was positive staining for S-100 protein, neuronspecific enolase, and vimentin. The tumor also stained for macrophage CD-68, α1-antichymotrypsin, and myoglobin. These immunohistochemical findings suggested the tumor cells to be undifferentiated mesenchymal cells which demonstrated the properties of neurogenic cells and histiocytes.

Once-Daily Use of Ofloxacin for Prophylaxis in Breast Cancer Surgery

The 150 consecutive patients who were hospitalized for breast cancer at our department between September 1992 and November 1995 were enrolled in this open study after having given their informed consent. Patients were assigned randomly to receive ofloxacin in daily doses of 200 mg to be taken in a single dose or a total dose of 600 mg divided into three doses postoperatively for 5 days. Ten patients (8 found to be without malignancies) were excluded from evaluation. Wound infections developed in 8 (12%) of the 69 patients in the 200-mg group and 12 (17%) of the 71 patients in the 600-mg group. Postoperative wound care lasted a median of 19 days (25th and 75th percentiles, 15 and 29 days) for patients given 200 mg and 16 days (13 and 25 days) for those given 600 mg; the difference was not statistically significant (Wilcoxon’s U test). Signs or symptoms suggesting ofloxacin toxicity were not observed, and several significant differences were found in laboratory test results between the two groups both before and after treatment. Abnormal changes after treatment were found in many individuals, but the rate of occurrence was similar in the two groups (U test). When ofloxacin is used for prophylaxis after breast surgery, we recommend a once-daily administration of 200 mg orally for financial reasons and increased patient compliance.

Cytologic Diagnosis of Estrogen and Progesterone Receptors in Breast Imprints

OBJECTIVE To investigate estrogen receptor (ER) and progesterone receptor (PR) levels in imprint specimens obtained at breast surgery and to compare their correlation with that of standard methods. STUDY DESIGN Imprint specimens for cytology were obtained from 101 mass-forming lesions in 66 patients, and specimens were frozen in liquid nitrogen for later assay. The imprint specimens were immunocytochemically (ICC) stained by monoclonal antibody to ER or PR; diaminobenzidine-stained cell nuclei in clusters were regarded as positive. Tissue specimens were assayed by the standard method of dextran-coated charcoal assay (DCC) and enzyme immunoassay. RESULTS Forty-five primary breast cancer lesions, 2 contralateral breast cancer, 49 dissected nodes and 5 benign breast lesions were collected. The correlation between DCC and ICC was 81% (82/101) for ER and 74% (66/101) for PR. That between EIA and ICC was 88% (88/99) for ER and 80% (79/100) for PR, higher than that between DCC and ICC for ER and PR. CONCLUSION ICC assessment of ER or PR on imprint cytology is a promising clinical test with an acceptable correlation.

Guidelines for the Assessment of the Therapeutic Efficacy of Antibiotics for Postoperative Infections in Japan (1997)

7Second Department of Surgery, Wakayama Medical School, Wakayama 2Digestive Center, Matsunami General Hospital, Gifu 3Department of Obstetrics and Gynecology, Kohtoh Hospital, Tokyo 4Department of Urology, National Hospital Kyushu Medical Center, Fukuoka SGeneral Surgery, Saitama National Hospital, Saitama 6Department of Mathematics, Kansai Medical University, Moriguchi ZDepartment of Clinical Pathology, School of Medicine, Juntendo University, Tokyo 8Third Department of Surgery, School of Medicine, Nihon University, Tokyo 9Institute of Medical Science, School of Medicine, St. Marianna University, Kawasaki 1~ of Surgery, Tokyo Dental College, Ichikawa General Hospital, Ichikawa ~Nagoya Municipal Kosei Hospital, Nagoya ~2Second Department of Surgery, Medical School, Osaka City University, Osaka 73Department of General Medicine, School of Medicine, Hiroshima University, Hiroshima, Japan

Prospective Randomized Study of Cyclophosphamide, Epirubicin, and 5-Fluorouracil versus Cyclophosphamide, Adriamycin, and 5-Fluorouracil in Advanced or Recurrent Breast Cancer.

BackgroundTreatment with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF), a widely used, potent regimen is sometimes restricted by the myelotoxicity and myocardiotoxicity of adriamycin (ADR). In a prospective randomized controlled study of patients with advanced or recurrent breast cancer, the efficacy and toxicity of a CEF regimen, in which epirubicin (EPI) was substituted for ADR, was compared with CAF.Methods138 female patients under 75 years of age who had unresectable or recurrent breast cancer during the period from October, 1989 to September, 1991, were randomized to one of two treatment regimens. The first regimen consisted of cyclophosphamide 100 mg p.o. d1-14, adriamycin 30 mg/mp2 i.v. d1, 8 and 5-fluorouracil 500 mg/mp2 i.v. d1, 8 (CAF). In the second regimen, EPI 30 mg/mp2 i.v. d1, 8 was substituted for ADR (CEF). Both regimens were delivered q4 weeks.ResultsOf 138 patients, 105 (CEF 56, CAF 49) were evaluable for response and survival, and all were evaluable for toxicity (CEF 68, CAF 70). The median course of lots CEF and CAF was 3 cycles. Response rates (complete response plus partial response) with CEF and CAF were 35.7% (20/56) and 36.7% (1 8/49), respectively. Adverse effects were similar in the two groups, but severe leukopenia (CEF 36.8%, CAF 64.3%) and hepatic toxicity (CEF 1.5%, CAF 12.9%) were encountered more frequently with CAF than with CEF. The duration of 50% survival was 135.9 weeks for CEF and 172.1 weeks for CAF (not significant).ConclusionAt an equal dose of EPI and ADR response rates and survival of the CEF group were similar to those of the CAF group, but adverse effects were fewer in the CEF group.