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Serum level of sex hormone-binding globulin (SHBG) was measured by immunoradiometric assay in fifty two breast cancer patients and twenty nine healthy female volunteers. The results are as follows: 1) Although the serum SHBG concentration showed no significant difference between the breast cancer group and the healthy control group, the serum SHBG concentration in postmenopause was significantly higher in the breast cancer group (63.8 +/- 31.2nmol/ml/ml; mean +/- S.D.) than in the healthy control group (40.1 +/- 15.4nmol/ml). 2) Subsequently in the postmenopausal breast cancer group, the serum SHBG concentration was significantly higher in the estrogen receptor (ER)-negative cancer group (97.8 +/- 12.7nmol/ml) than in the ER-positive cancer group (55.8 +/- 32.1nol/ml). 3) No significant relationships were showed between the serum SHBG concentration and obesity or serum estradiol concentration in postmenopausal patients. 4) The serum SHBG concentration showed significant decrease 3 months after radical operation for breast cancer in postmenopausal patients. These results suggest the possibility of the SHBG synthesis in breast cancer tissue.

The purpose of this study was to investigate the biological behavior of male breast cancer. We evaluated 11 cases of male breast cancer with respect to tumor growth, extent of disease, hormone receptor status, and histological grade of the malignancy, in comparison with 241 cases of female breast cancer. The duration of symptoms was 8.6 +/- 9.1 months in males and 8.5 +/- 18.6 months in females. The incidences of stages I, II, and III were 46%, 27%, and 27%, respectively, in male breast cancer, and 38%, 49%, and 13% in female breast cancer. Metastasis to the lymph node was negative in 60% of the male patients and 54% of the female patients. All cases of male breast cancer were histologically grade I according to Bloom's classification; the histological grades were as follows for the female breast cancer cases: grade I in 99 patients, grade II in 87, and grade III in 55. The rates of hormone receptor positively were 89% for ER and 86% for PgR in male breast cancer, and 64% for ER and 44% for PgR in female breast cancer. Therefore, there was no significant difference in the growth of male breast cancer and female breast cancer, but in male breast cancer the rate of hormone receptor positivity was high, endocrine therapy was effective, and the histological grade was low. Accordingly, the result following appropriate treatment of male breast cancer should be at least comparable to the results with female breast cancer.

A new impedance analytical system was developed, and measurements were performed over a frequency range of 0-200 kHz by the three-electrode method. The three electrodes consist of a coaxial needle electrode inserted into the tumor and a large reference electrode on the upper abdominal wall. The electrical bio-impedance was measured in 54 patients with breast tumors. The biological tissue can be regarded electrically as an equivalent consisting of extracellular resistance (Re), intracellular resistance (Ri), and electrical capacitance of the cell membrane (Cm). These three parameters were calculated from the measured values of electrical bio-impedance by the curve-fitting technique using a computer program. It was found that Re and Ri of breast cancers were significantly higher than those of benign tumors (p less than 0.01), and that Cm of breast cancers was significantly lower than that of benign tumors (p less than 0.01). Measurement of the electrical bio-impedance of breast tumors may have value in the differential diagnosis of breast lesions.

We studied valvular regurgitation (pulmonary, aortic, tricuspid and mitral regurgitation) in 30 patients with complete heart block by color Doppler echocardiography, pulse Doppler and continuous wave Doppler echocardiography. The prevalence rate of multivalvular regurgitation of these subjects was 83.3%. Regurgitation involving all four valves appeared in 30.0% of these patients. The prevalence rate of pulmonary, aortic, tricuspid and mitral regurgitation was 56.7%, 33.3%, 100%, and 76.7% respectively. Pulmonary regurgitation (PR) was observed in patients with complete heart block without pulmonary hypertension. PR velocity was slow and interrupted by atrial contraction. It might be possible to evaluate atrial pressure from the interruption of PR. Tricuspid regurgitation (TR) during systole was often present in patients with right ventricular endocardial pacing. Systolic TR was influenced by atrial contraction. When atrial contraction occurred during systole, TR was interrupted, or shortened. Diastolic TR and MR were easily detected by M mode color Doppler echocardiography. The diastolic TR and MR were of slow velocity and appeared 240-290 msec after P wave. These atypical valvular regurgitation in patients with complete heart block reflect of the inverse atrial-ventricular pressure gradient across the atrio-ventricular valve.

A patient with stage IV advanced breast cancer with multiple metastasis (bones of the whole body, lungs) were treated by ovariectomy, administration of an non-steroidal antiestrogen (tamoxifen) and mild chemotherapeutic drugs, with favorable results. After four years, however, the patient had a relapse of the cancer. A steroidal antiestrogen (epitiostanol) was then administered with satisfactory results. When a breast cancer relapse occurs in patients once treated successfully with endocrinotherapy, a different form of endocrinotherapy should be tried. There is a possibility that the mechanism of action of Epitiostanol, which is regarded as a steroidal antiestrogen, is different from that of tamoxifen in which an estrogen receptor (ER) system is included.

Tamoxifen was administered over a period of 4 weeks to 19 female Sprague-Dawley rats bearing 20 DMBA-induced mammary tumors. Consequently, 13 tumors (65.0 per cent) regressed and showed a reduction in their estradiol receptor (ER) and progesterone receptor (PgR) concentrations. In spite of subsequent treatment given to the rats bearing the regressed tumors, 6 new tumors occurred. The ER and PgR concentrations of these tumors were lower than those of the tumors before tamoxifen therapy, and histochemical study showed these tumors to be composed mostly of ER-negative cells. These results suggest that: (a) the hormone dependency of breast cancer is reduced by tamoxifen therapy; (b) breast cancers recurring during tamoxifen therapy show reduced hormone dependency.

The effect of adriamycin (ADM) infused intraarterially as a preoperative procedure was analyzed retrospectively in 15 patients with primary advanced breast cancer. A high clinical response rate (CR+ PR) of 73% (11/15) was obtained by the treatment, and also remarkable degenerative changes of tumor cells were histologically noted in 10 out of 15 surgical specimens (67%). A correlation between the dose of ADM infused and the rate of tumor regression was observed. A significantly higher concentration of ADM was detected in metastatic lymph nodes and tumors obtained 3-4 weeks after intra-arterial infusion of ADM than that in normal mammary gland. As for side effects, alopecia, leukocytopenia, anorexia, nausea and vomiting occurred at high frequencies. The side effects due to this treatment were considered to be tolerable. Prognostically, a good survival rate was not observed using preoperative treatment with intra-arterial ADM infusion.

Cefadroxil was administered at a daily dose of 50 mg/kg in 113 children including acute respiratory tract infections suspected to be a bacterial infection and other febrile diseases. Among 41 cases in which pharyngeal culture was made twice before and after administration or urine and feces cultures were made, 20 cases (48.8%) were good bacteriologically, 5 cases (12.2%) were poor, and 16 cases (39.0%) were unknown. Clinical efficacy was obtained in 105 cases (92.9%) out of 113 cases. Microbial substitution was noticed in 12 cases (29.3%) out of the cases of which pharyngeal culture was made after cefadroxil administration. Haemophilus influenzae was detected newly after the administration in 7 cases (58.3%) out of these 12 cases. Bacteriological efficacy was obtained in 5 cases of acute respiratory tract infection of which pathogen was considered to be Haemophilus influenzae. No microbial substitution was noticed in these 5 cases. As to the side effects of cefadroxil administration, only a slight diarrhea was observed in 2 cases.

The relationship of hormone receptor and postoperative prognosis was investigated in 166 patients with breast cancer who underwent curative operation and postoperative adjuvant chemotherapy. The endocrine therapy was performed only for the patients with recurrent disease. The content of estrogen receptor (ER) and progesterone receptor (PgR) were measured by binding assay using gel-filtration method. ER-positive cases accounted for 56% of 166 patients and PgR-positive ones for 36% of 124. The relapse free interval was not different between the ER-positive group and ER-negative one, but the survival curve after relapse was significantly different between the both groups. There was no significant difference in the relapse free interval and the survival curve after relapse between PgR-positive group and PgR-negative one. These results suggest that the ER is a good predictor as to the response to endocrine therapy given for recurrent disease, but not as to early recurrence.

The occurrence of a systolic sound in hypertrophic obstructive cardiomyopathy (HOCM) has been well known for more than 20 years. This was phonoechocardiographically regarded as the sound coincident with the abrupt halt of the systolic anterior movement (SAM) of the mitral valve echo, and it has been termed the SAM sound. A 58-year-old man with HOCM was admitted with right hemiplegia. He was found to have a SAM sound which waxed and waned in intensity, and at times moved earlier into systole. He was studied by cardiac catheterization, M-mode and two-dimensional Doppler echocardiography (pulsed, continuous wave and color flow Doppler methods). Asymmetric septal hypertrophy (interventricular septal thickness = 25 mm, left ventricular posterior wall thickness = 14 mm), as well as SAM and midsystolic aortic valve closure were demonstrated. The presence and intensity of the sound was not related to rhythm (normal sinus rhythm vs atrial flutter), heart rate, respiration, position, or inhalation of amyl nitrite. Two-dimensional Doppler echocardiography revealed the following: 1. In the left ventricular outflow tract just below the aortic valve, a systolic turbulent flow was always present. 2. In the left ventricular chamber near the apex, a systolic laminar flow was interrupted in those cycles where the SAM sound was present. Otherwise, in cycles lacking the SAM sound, laminar flow in this locality continued throughout systole (even shorter duration than normal). 3. In the left ventricular inflow tract, diastolic flow was unaffected by the presence of the sound. 4. No mitral regurgitation was observed using color flow Doppler echocardiography. In summary, a SAM sound appeared to be associated with sudden deceleration of blood flow from the apex to the mid left ventricle.

Four patients with mitral valve prolapse and ventricular tachycardia or fibrillation were described. Case 1 was a 46-year-old man with syncope due to ventricular fibrillation. Case 2 was a 36-year-old woman with palpitation and dizziness due to ventricular tachycardia. Case 3 was a 47-year-old man with palpitation and dizziness due to ventricular tachycardia. Case 4 was a 38-year-old man with syncope due to torsade de pointes. Left ventriculograms showed mitral valve prolapse in all cases. Coronary arteriograms were also normal, supporting a noncoronary etiology of the arrhythmia. Patients with unexplained ventricular arrhythmias should be screened for mitral valve prolapse.

5'-DFUR was administered orally to recurrent breast cancer patients at a daily dosage of 1,200 mg given 3 times a day for more than 8 weeks. Out of 16 evaluable cases, 1 CR, 5 PR, 5 NC and 5 PD were observed, and the overall response rate was 37.5%. There was no significant difference in the response rate between the patient with or without prior fluorinated pyrimidine therapy, or between sites of the lesion. Toxic effects consisted of gastrointestinal toxicity such as diarrhea (25%), anorexia (12.5%), abdominal pain (12.5%) and nausea and vomiting (6.3%). No other severe side effect was observed. These results suggest that 5'-DFUR can be useful for the treatment of breast cancer.

The aim of this study was to establish the role of estrogen receptor (ER) and progesterone receptor (PgR) as prognostic indicators for early recurrence and survival. In all, among breast cancer patients, 166 patients who had undergone radical or extended radical mastectomy were studied. These patients were treated with adjuvant chemotherapy alone for 2-3 years after surgery. No patients had adjuvant endocrine therapy. Local recurrence and/or distant metastases were treated by endocrine therapy and/or chemotherapy. The relapse-free interval was not different between the ER-positive and ER-negative patients. The postrelapse survival curve was significantly different between the two groups. There was no significant difference in the relapse-free interval and the postrelapse survival curve between the PgR-positive and PgR-negative patients. These results suggest that ER is a good predictor of the response to endocrine therapy given after relapse, but not of early recurrence.

A 63-year-old man who had been aware for 5 years of a tumor near his left nipple was admitted complaining of rapid tumor enlargement. He received standard mastectomy under the diagnosis of breast sarcoma. The regional lymph nodes were not involved and the excised tumor was 12.0 cm in diameter it showed a grayish-white cut surface and a sharp border. Histologically we made a diagnosis of stromal sarcoma of the breast showing diffuse proliferation of spindle shaped cells with high cellularity, moderate atypia and scattered mitosis. Postoperatively, he underwent chemotherapy with cyclophosphamide. Two years and five months after the operation, he is alive and well without any sign of recurrence.

Cefoperazone (CPZ) at dose levels of 80 approximately 100 mg/kg/day, divided 3 approximately 4 times, was drip-infused or intravenously injected for a period of 2 approximately 6 days to 10 patients. All 10 cases, 4 cases of bronchopneumonia from which H. influenzae was detected (Group A S. pyogenes and S. pneumoniae were also detected in each 1 case). 2 cases of coli urinary tract infection, 1 case of acute colitis from which pathogenic E. coli was detected, 1 case of E. coli carrier, 1 case of acute bronchitis (bacteria were not detected), and 1 case of urinary tract infection (bacteria were not detected) showed rapid improvement of clinical symptoms with rapid eradication of the pathogenic bacteria. In one case of urinary tract infection where S. epidermidis and S. faecalis were simultaneously detected, S. epidermidis was removed but S. faecalis was merely decreased. The effective antibacterial concentration after intravenous injection of CPZ in the feces was determined and found to be present in sufficient concentrations to prevent colon infection. No particular side effects were observed during CPZ therapy.

In a review of 549 cases of breast cancer in the last 16 years, 7 cases with lobular carcinoma have been studied. All of the patients appeared well and were without recurrence. Two cases had been lobular carcinomas in situ, one of which had arisen in a small fibroadenoma associated with malignant phyllodes tumor in the opposite breast, and the other had shown multicentric foci of a lobular neoplasm. The remaining 5 cases had been invasive lobular carcinomas. The incidence of lobular carcinoma represented 1.3% (7/549) of all primary breast carcinomas, and had been increasing chronologically. Estrogen and progesterone receptors were positive in 5 eligible cases.

In 141 mastectomy specimens, performed for invasive or non-invasive carcinomas, histopathologic study was performed to assess the extent of nipple-areola involvement by the tumor. In this study, patients were excluded when 1) the tumor was located beneath the areola, 2) nipple and/or areola abnormalities were clinically present. Tumor involvement of the nipple and/or areola was found in 44 of 141 specimens (31%), with intraductal growth in 36 (82%) of 44, stromal invasion in 3 (7%) and ductal & stromal invasion in 5 (11%). Analysis of nipple-areolar involvement with consideration of the different variables indicates that it occurred in association with tumor size, tumor-areola distance and histological type. Such information provides clinically relevant guide lines in decision making for limited breast surgery.

In 175 women with mucinous carcinoma (MC) of the breast, the morphologic features, the clinicopathological features (age, tumor size, and nodal status) and prognoses were investigated. They were divided into two types, those with "unmixed type" (n = 140) showing no component of invasive ductal carcinoma (IDC) and "mixed type" (n = 35) including an IDC component. The unmixed type showed less frequent (P less than 0.01) nodal involvement and a higher degree (P less than 0.005) of extracellular mucus production than the mixed type. The presence of nodal metastases showed no correlation with the degree of mucus production. The 10-year survival rate of the unmixed type (90.4%) was better (P less than 0.001) than in the mixed type (66.0%). In the unmixed type, a higher level of mucus production showed trends toward a better prognosis, younger age and smaller tumor size (P less than 0.01). In the mixed type, the degree of mucus production showed no significant correlation with either the age, tumor size, or prognosis. It is more important for the prognosis of patients with MC to have no IDC component than to show abundant mucus within the tumor.

To evaluate the accuracy in diagnosing breast lesions by frozen sections, 657 consecutive diagnostic biopsies seen during 1982 were reviewed. Of 559 lesions considered benign at frozen sections, 558 were also benign in paraffin sections, the remaining one being a papillary carcinoma (i.e. 1/559 or 0.2% false negative). All 78 cases diagnosed as malignant in frozen sections were also malignant in paraffin sections (i.e. 0% false positive). Of the 20 doubtful cases, in frozen sections, 15 showed a papillary lesions; 7 of them were malignant in paraffin sections and the rest 13 benign. It is concluded that the frozen sections are usefull in the diagnoses of mammary disorders except for those cases with papillary tumors.

In 141 mastectomy specimens, performed for invasive or noninvasive carcinomas, histopathologic study was performed to assess the extent of nipple-areola involvement by the tumor. In this study, patients were excluded if the tumor was located beneath the areola; and nipple and/or areola abnormalities were clinically present. Tumor involvement of the nipple and/or areola was found in 44 of 141 specimens (31%), with intraductal growth in 36 (82%) of 44, stromal invasion in 3 (7%), and ductal and stromal invasion in 5 (11%). Analysis of nipple-areolar involvement with consideration of the different variables indicates that it occurred in association with tumor size, tumor-areola distance, and histologic type. Such information provides clinically relevant guidelines in decision making for limited breast surgery.

Between 1972 and 1981, 4 women with breast sarcoma underwent treatment at our department; they accounted for 1.1% (4 of 355) of all female breast malignancies. There was one case of malignant lymphoma and liposarcoma each, and 2 cases of malignant cystosarcoma phyllodes. The patients averaged 31.0 years of age. Of the two cases of cystosarcoma phyllodes, one had coexisting lobular carcinoma in situ arising in a fibroadenoma of the contralateral breast, the other had a coexisting lung cancer. Mastectomy was performed in 3 cases, irradiation in one (malignant lymphoma). All patients received concurrent chemotherapy. The regional lymph nodes were not involved, and 2 patients are alive and well without recurrence.

In Tokushima prefecture, mass screening for breast cancer has been conducted using physical examination alone since 1970. Breast cancer was detected in 108 of 141,116 screened women up until 1986. The detection rate was 0.08% among total examinees, 0.12% among initial examinees, and 0.04% among subsequent examinees. Patients with breast cancer were divided into three groups. Group I consisted of 70 patients whose cancers were detected by initial screening examination. Group II consisted of 38 patients whose cancers were discovered by subsequent periodic screenings. Group III included "interval" patients, whose cancers were found in the interval within 2 years between a negative screening examination and the next screening; 19 patients were classified into this group. Serving as controls were 615 breast cancer patients who visited our outpatient clinic, independently of the screening program, during the same period as that of the mass screening. Of the 108 patients in Groups I and II, 51 patients (47%) had noticed a lump in the breast themselves by the time of the mass screening. The stage classification and nodal involvement showed significant differences between the mass screening group and the control group, but no significant differences among the three groups. The Group III cases (interval cases) were detected at an early stage, but some of these cases included patients with fast-growing tumors. When compared with cumulative survival curves according to age-matched case-control study, there was no significant difference between the patients whose tumors were detected in the mass screening and the controls.

Cefuroxime (CXM) was administered to 11 patients with pediatric bacterial infections, and clinical effective results were obtained in all these cases. Causative organisms detected in 5 cases with respiratory tract infection, and with urinary tract infections were all eliminated, and the bacterial count decreased in patients with colitis. As for side effect, 1 case developed eosinophilia, and another case with impaired liver function as underlying disease showed transitory exacerbated examination values. Time-course determinations of blood levels and urinary excretions were performed in 1 case. Fecal levels were determined in 2 cases but could not be detected; inactivation action of CXM was observed from the same fecal filtrate.

A clinicopathological study was performed on characteristics of mammary mucinous carcinoma and its 3 pathological subgroups: "gelatinous type"--with predominant mucin component, "epithelial type"--with predominant epithelial component, and "combined type"--with a small part of infiltrating ductal carcinoma and mucinous pattern. Among 4,653 primary breast cancers mastectomized at the C.I.H. between 1946 and 1981, 160 or 3.4% was mucinous carcinoma. They were divided into 106 gelatinous type, 20 epithelial type and 34 combined type. 10-year survival rate of mucinous carcinoma (75.3%) was better than whole breast cancer (65.6%). And it was 90.7%, 82.4% and 67.6% in gelatinous, epithelial and combined type, respectively.

A case is reported of a patient who developed a histological unusual sarcoma in the chest wall 5.3 years after postoperative radiation therapy (5,000 rads) for breast cancer. This sarcoma showed microscopic features of malignant fibrous histiocytoma (MFH). A review of the literature disclosed 16 other cases in which MFH developed under similar circumstances. An analysis of these 16 cases and the case reported here showed that the mean radiation dose was 5,623 rads, that the time period between irradiation and the development of MFH ranged from 2 to 27 years and that wide resection offered better prognosis than chemotherapy.

Cases of early invasive mucinous carcinoma of the breast have been reviewed. Microscopically, a typical lesion exhibits leakage of cancerous mucus into the stromal tissue from an intraductal carcinomatous component which were shown to be mucus-producing and to be lower papillary projection. Among 5,360 primary breast cancers that had been mastectomized at the C.I.H., 11 or 0.21% were determined as being "early" cases. All of these cases exhibited "pure type" mucinous carcinomas which were found to be highly mucus. The average age of these patients was 41 years (range: 34-51 yrs.), and no cases showed a nodal involvement. During an average follow-up of 8 years, no recurrent case were found. Thus, we have found that these "early" cases revealed an early invasion of a mucinous carcinoma that is highly mucus-producing but without an invasive ductal carcinomatous pattern.

In Tokushima prefecture, mass screening for breast cancer has been conducted using physical examination alone since 1970. Breast cancer was detected in 116 of 111,571 screened women up until 1984. The detection rate was 0.08 per cent in total examinees, 0.13 per cent in initial examinees, and 0.04 per cent in subsequent examinees. The patients with breast cancer were divided into three groups, i.e., 62 cases detected at initial screening, 28 cases detected at subsequent screenings, and 26 interval cancer cases. 510 patients with breast cancer in the outpatient clinic were serving as controls. The stage classification and nodal involvement were significantly different between the mass screening group and the control group, but not significantly different among the three groups. The interval cases were detected at an early stage. The survival rates were not significantly different between the three groups and the control group. Efforts should be doubled to educate women about the proper method of breast self-examination in order to promote the early detection of breast cancer.