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Purpose: Physiological FDG uptake in the stomach is a common phenomenon, especially noted at the cardia. Water intake just before scanning will result in gastric distention and thinning of the gastric wall, which in turn may lead to a reduction in the physiological uptake in the gastric wall. In the current study, we investigated whether gastric distention by water intake just before PET imaging reduces physiological FDG uptake in the stomach., Methods: The patient population comprised 60 patients who underwent whole-body FDG-PET imaging for cancer screening following gastroscopy performed within the preceding week. All patients took 400 ml of water for hydration and were administered 185 MBq of FDG intravenously. The patients were randomly divided into two groups: a group with additional water intake (AW group; n = 30) and a group without additional water intake (NW group; n = 30). In the AW group, an additional 400 ml of water was given just before PET imaging. For quantitative analysis, the stomach was classified into three areas [upper (U), middle (M) and lower (L)], and the degree of FDG uptake in each area was evaluated using standardised uptake values (SUVs)., Results: In the NW group, the mean SUVs in the U, M and L areas were 2.41 +/- 0.75, 2.28 +/- 0.73 and 1.61 +/- 0.89, respectively, while in the AW group they were 1.82 +/- 0.66, 1.73 +/- 0.56 and 1.48 +/- 0.49, respectively, and 2.21 +/- 0.38 in the oesophago-gastric junction. The mean SUVs in the U and M areas in the AW group were significantly lower than those in the NW group (p < 0.05)., Conclusion: Additional water intake just before PET imaging is an effective method for suppressing physiological FDG uptake in the stomach.

Multicentric Castleman disease is a systemic lymphoproliferative disease with incomplete understood etiology. The various renal complications of this disease may include minimal change disease, mesangial proliferative glomerulonephritis, membranous glomerulonephritis and nephrotic syndrome, caused by secondary amyloidosis. In several reported cases of localized Castleman disease associated with renal amyloidosis and nephrotic syndrome, resection of organs involved by lymphoid proliferation resulted in complete remission. However, therapy of multicentric Castleman disease with renal amyloidosis is not well-established. We treated a case of a 39-year-old woman with multicentric Castleman disease complicated by nephrotic syndrome caused by secondary AA amyloidosis. The patient underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), achieving complete remission. Autologous stem cell transplantation may be an attractive choice in therapy for refractory multicentric Castleman disease.

Background: To evaluate the efficacy and toxicity of vinorelbine (VNB) with doxorubicin/cyclophosphamide (AC) combination chemotherapy, a phase I-II study was carried out in patients with advanced or recurrent breast cancer., Methods: The phase I part of this study was carried out to determine the treatment schedule and acceptable dose of VNB for the phase II study. In phase I, VNB was initially given as a short infusion on days 1, 8 and 15, every 4 weeks. The initial dose of vinorelbine was 15 mg/m2. In the AC regimen, 20 mg/m2 of doxorubicin (ADM) was given intravenously (i.v.) on days 1 and 8, and 100 mg/body of cyclophosphamide (CPA) was administered orally from days 1 to 14. Subsequently, a phase II study was carried out at the maximum acceptable dose (MAD)., Results: Twenty-three patients were entered into this study. In patients receiving VNB at a dose of 15 mg/m2, neutropenia (> or = grade 3) frequently occurred on day 15. The treatment schedule of this study was therefore changed to VNB given i.v. on days 1 and 8 with AC combination chemotherapy. In this treatment schedule, grade 4 neutropenia lasting for more than 4 days occurred in patients given VNB at a dose of 20 mg/m2 with AC more frequently than in those given 15 mg/m2 of VNB. Therefore, the MAD of VNB was determined to be 20 mg/m2 in this regimen. At this recommended dose, there were 1 complete (CR) and 8 partial responses (PRs) in 15 patients, with an overall response rate of 60.0%. No treatment-related death occurred., Conclusions: These data indicate that VNB plus AC combination chemotherapy was effective and well tolerated for breast cancer patients. A randomized trial of VNB plus AC vs. AC combination chemotherapy may be required to ascertain the benefit of this regimen for advanced or recurrent breast cancer patients.

We studied the usefulness of the oral 5-FU anti-cancer drug 1-hexylcarbamoyl-5-fluorouracil (HCFU) + cyclophosphamide (CPM) + tamoxifen (TAM) (HCT group) in comparison with CMF + TAM (CMFT group) in adjuvant therapy for breast cancer by a non-inferiority study based on a multi-institutional joint study. Clinical stage I, II primary breast cancers with histologically positive axillary lymph node metastasis were randomly assigned to the HCT group or the CMFT group after primary surgery. We registered 136 cases (HCT group 68 cases, CMFT group 68 cases). No significant difference in the 5-year overall survival rate (OS) and the 5-year disease-free survival rate (DFS) was found between the two groups. In the stratified analysis, DFS in cases in which the number of metastatic lymph nodes was 1-3 was significantly better in the HCT group (HCT group 84.3%, CMFT group 69.4%, log-rank test p=0.0496). No significant difference in the total incidence of adverse effects was found between the two groups, but there were significantly less adverse effects of grade 2 or over in the HCT group (p=0.034). The QOL survey at 3 months after surgery showed a significant decline of the QOL regarding lassitude, degree of difficulty in daily life, satisfaction with treatment and present mood in the CMFT group. Study results suggest that 2-year HCT therapy including the oral 5-FU anti-cancer drug HCFU is a useful adjuvant therapy which can replace CMFT therapy in early breast cancer cases with 3 or lower metastatic lymph nodes.

Background: Experience with conserving surgery for lobular carcinoma has grown as more breast conserving surgeries have been performed. We examined the results of breast conserving therapy in lobular carcinoma., Patients and Methods: We examined the postoperative positive margin rate, presence or absence of additional surgery, presence or absence of local or systemic recurrence and role of breast helical CT in 25 cases of breast conserving surgery performed at this department from 1991 through June 2003., Results: Among the 303 cases of all breast conserving surgeries, there were 63 case with positive margins (20.8%), but there were 15 of 25 positive margin cases (60.0%) among the lobular carcinoma cases. In 8 of the 15 positive margin cases the technique was changed to mastectomy. One case of recurrence in the breast has been observed thus far. Although the positive margin rate and positive margin rate in infiltrating carcinoma cases tended to decline after the introduction of breast helical CT, the rates remained high., Conclusions: Since the positive margin rate was significantly high at the time of breast conserving surgery for lobular carcinoma, careful selection of technique based on imaging studies such as breast helical CT and MRI along with careful follow-up is considered necessary.

Background: Although many clinical data regarding breast-conserving treatment have already been reported from European and North American countries, few clinical data with long-term follow-up have been reported from Japan., Method: We collected information on therapeutic and possible or developed prognostic factors and follow-up data for Japanese women who had received breast-conserving treatment consisting of wide excision of the primary tumor, axillary dissection and radiotherapy for unilateral breast cancer considered suitable for breast-conserving treatment from 18 Japanese major breast cancer treating hospitals; 1561 patients were registered., Results: The median follow-up period was 77 months. Five-year disease-free and overall survival rates were 89.4 and 95.9%, respectively. The 5-year local recurrence-free rate was 96.3%. The patients with histologically positive margins (P < 0.0001) or estrogen receptor negative tumor (P = 0.0340) or younger than 40 years old (P < 0.0001) developed statistically significantly more local recurrences. Adjuvant endocrine therapy was essential for the estrogen receptor positive patients to have a lower local recurrence rate. Endocrine therapy did not change the local recurrence rate among estrogen receptor negative patients at all. Multivariate analysis showed histological margin status and the combination of estrogen receptor status and endocrine therapy were independent prognostic factors for local recurrence., Conclusion: The 5-year local recurrence rate of Japanese breast cancer patients who were treated with breast-conserving treatment using radiotherapy was 3.7%. Independent prognostic factors for local recurrence were histological margin status and the combination of estrogen receptor status and adjuvant endocrine therapy.

Objective: We conducted a prospective multicentre, collaborative randomised study on postoperative adjuvant therapy in patients with stage II primary breast cancer to evaluate the effect of a combination of tegafur and uracil (UFT) on tamoxifen (TAM) plus mitomycin (MM) in patients with estrogen-receptor-positive [ER(+)] breast cancer and TAM on UFT + MM in patients with estrogen-receptor-negative [ER(-)] breast cancer., Methods: MM (13 mg/m(2)) was intravenously administered on the day of surgery for all patients, after which patients with ER(+) were randomised to TAM 20 mg/day (treatment A) or TAM 20 mg/day and UFT 400 mg/day (treatment B). Patients who were ER(-) were randomly allocated UFT 400 mg/day (treatment C) or TAM 20 mg/day and UFT 400 mg/day (treatment D). TAM and UFT were administered orally for 2 years, starting on day 14 after surgery., Endpoints: 5-year disease-free survival (5y DFS), 5-year overall survival (5y OS), and safety., Results: The study commenced in November 1988 and the data cut-off was May 1997 after follow-up of the last patient for 5 years. A total of 765 patients with stage II breast cancer were enrolled. 436 patients with ER(+) [group A: 213, group B: 223] and 317 patients with ER(-) [group C: 162, group D: 155] breast cancer were eligible for this study. The rate of 5y DFS was 83.1% for group A and 90.7% for group B (p = 0.020). There was a significant difference in 5y DFS between the two groups among postmenopausal and positive lymph node metastases patients. The incidence of adverse reactions was 4% for group A and 18% for group B (p < 0.05). The rate of 5y DFS was 77.1% for group C and 85.5% for group D (p = 0.063). The rate of 5y OS was 84.7% for group C and 89.8% for group D (p = 0.216). The incidence of adverse reactions was 18% in group C and 11% in group D (p = 0.06)., Conclusion: UFT in combination with TAM + MM showed higher efficacy than TAM + MM as a postoperative combination therapy for breast cancer in patients with ER(+) breast cancer. A trend was observed in favour of the addition of TAM to UFT + MM in postmenopausal and lymph node metastases-negative patients with ER(-) breast cancer.

We report that single agent therapy with trastuzumab had a significant effect on metastatic breast cancer, which was confirmed to be HER2 positive by Herceptest showing 2+staining, and gene amplification positively detected by FISH analysis. A 48-year-old woman underwent extended radical mastectomy (T2N0M0 stage II). Three years after the operation supraclavicular lymph node metastasis was noted. Bone scintigraphy showed metastases to the left ribs 5 years after operation. She was treated with chemo-endocrine therapy, but nonetheless could not bear the back pain caused by the bone metastases. Another chemotherapy course could not be permitted because of leukopenia. Immunohistochemistry (IHC) analysis with Herceptest showed 2+staining for HER2 and FISH analysis showed gene amplification of HER2. We started single agent therapy with trastuzumab and she subsequently had remarkably improved back pain. Physical examination and ultrasonography showed disappearance of the previous palpable supraclaviclar lymph nodes. Serum tumor markers were also reduced after the first administration of trastuzumab. The patient is currently alive, with no further progression of the lymph node or bone metastases.

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.

A new generation type of vinca alkaloid, vinorelbine (VNR), is a promising agent for the treatment of breast cancer patients. As a first line treatment for metastatic breast cancer, combination chemotherapy including anthracyclines plus VNR has demonstrated a high response rate and tolerability. In addition, other VNR containing regimens, such as 5-fluorouracil plus VNR, produced a 64% response rate. This evidence suggests VNR-containing combination chemotherapy may be a promising first-line treatment for breast cancer patients. In Japan, VNR is not registered, but a late phase II study has been completed. An approximately 30% response rate was obtained with its use as a monotherapy. In addition, a phase I/II study of combination VNR plus AC (adriamycin + cyclophosphamide) has been conducted. At the present time, the results are being analyzed.

Background: Pyrimidine nucleoside phosphorylase (PyNPase) is the enzyme that converts 5'-deoxy-5-fluorouracil (5'DFUR) to 5-fluorouracil (5FU). Its activity in cancer tissue may correlate with the selective antitumor activity of 5'DFUR in breast cancer., Methods: Two hundred and sixteen T2 breast cancer patients were treated consecutively with surgery followed by 5'DFUR (600 mg/body/day) + tamoxifen (20 mg/body/day) for 2 years. PyNPase activity in breast cancer tissue, determined by high-performance liquid chromatography, ranged from 4.2-626.0 micrograms FU/mg protein/hr (mean +/- SD, 203.5 +/- 122.4), and the examined patients were divided into two groups: group A (high PyNPase group), cases with the PyNPase activity equal to or more than the mean value of 203.5 micrograms FU/mg protein/hr, and group B (low PyNPase group), cases with activity less than the mean value., Results: Although there was no difference in relapse-free survival (RFS) between groups A and B, among node-positive patients (n = 83) those in group A tended to have a longer RFS. When divided into subgroups according to estrogen receptor (ER) status, among node-positive and ER-positive tumors (n = 49), the RFS was significantly better in group A than in group B (p < 0.05)., Conclusion: Intratumoral PyNPase activity might be of use as a predictor of the effect of adjuvant 5'DFUR on breast cancer.

A trial was designed to examine the combination of UFT and mitomycin (Mutamycin) plus tamoxifen (Nolvadex) as postoperative adjuvant therapy in the treatment of patients with stage II, estrogen receptor (ER)-positive primary breast cancer. Mitomycin was administered intravenously at 13 mg/m2 on the day of surgery. Patients judged to be ER-positive were randomly allocated to either group A, which received oral tamoxifen 20 mg/day 14 days after surgery for 2 years, or group B, receiving oral UFT 400 mg/day plus tamoxifen 20 mg/day. A total of 219 patients were enrolled in group A, of which 213 (97.3%) were determined to be eligible; 225 patients enrolled in group B and 223 (99.1%) were eligible. The 5-year survival rates were 93.0% for group A and 95.4% for group B, with no significant difference between groups. The 5-year relapse-free survival rates were 83.1% for group A and 90.7% for group B, a significant advantage (P = .020) for the UFT plus tamoxifen group. Combination therapy with mitomycin, tamoxifen, and UFT proved to be an effective postoperative chemoendocrine therapy for stage II, ER-positive breast cancer.

Background: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from breast cancer by hepatic intra-arterial infusion chemotherapy, no phase I study including pharmacokinetic analysis has been reported. We performed a phase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in patients with advanced or recurrent breast cancer., Methods: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m2 adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1 through day 14 every 28 days. At least two cycles were required before evaluation. Twenty-eight patients were entered into this study and 26 patients were evaluable. Seventeen patients had hepatic metastasis only, although nine patients had additional metastasis to other sites., Results: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occurred at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There were 11 catheter-related complications which were not dose dependent. Seven out of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+)., Conclusion: Hepatic arterial infusion therapy appears to be safe and effective but catheter-related complications must be overcome before starting a phase III trial.

Seventy-two patients with Stages III and IV (TNM, UICC, 1987) squamous-cell carcinoma of the oropharynx and hypopharynx (oro-hypopharyngeal cancer) were treated with external irradiation, or irradiation plus 13.56 MHz radiofrequency (RF) capacitive hyperthermia from 1989 to 1995. This study compared initial response, histological effect and 5-year survival rate of thermoradiotherapy (TRT) group with those of radiotherapy alone (RT) group. In the TRT group, 15 patients were treated definitively, and 18 patients preoperatively. In the RT group, 15 patients were treated definitively, and 24 patients preoperatively. With definitive irradiation, the complete response rate of the primary lesions was 73% in the TRT group and 27% in the RT group (p = 0.009) and the complete response rate of the metastatic lymph nodes was 80% in the TRT group and 27% in the RT group (p = 0.005). With preoperative irradiation, the pathological CR (No residual cancerous cells) rate of the primary lesions was 56% in the TRT group and 8% in the RT group (p = 0.01), and the pathological CR rate of the lymph nodes was 72% in the TRT group and 21% in the RT group (p = 0.001). The 5-year survival rates with definitive irradiation were 47.6% in the TRT group and 18.7% in the RT group (p = 0.025). Thus TRT was more effective than RT for advanced oro-hypopharyngeal cancer.

Background: The mammalian mandible develops around Meckel's cartilage and other secondary cartilages, including the dentary. There have already been many studies of the development of the rat mandible that have employed histological serial sections. However, no previous investigators have captured the three-dimensional features of the developmental process., Methods: In this study, the technique of double staining with alizarin red S and alcian blue was employed directly on whole body specimens to investigate the three-dimensional development of the rat mandible., Results and Conclusions: We found that the molar socket obstructs the developing mandible, causing it to emerge medial to Meckel's cartilage. Our results also indicate that the secondary mandibular cartilages may contribute to supplementary growth in response to local factors.

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.

To confirm the 1994 findings of Okuzumi, Haishi, and Kokubun, the displacement of the center of foot pressure, one-foot balance and head sway were measured in children with Down syndrome (n = 11) compared to those with other types of mental retardation (n = 17). The magnitudes of the displacement of the center of foot pressure and head sway were not significantly different between the Down group and other forms of mental retardation, whereas the performance of one-foot balance was significantly lower in the Down group. The mean frequencies of sway waves were generally higher in the Down group, and the differences between the two groups were significant except for sagittal head sway. The results generally supported the prior findings. We proposed that it was not the magnitude of the displacement of the center of foot pressure but rather the manner of the whole body's sway which might be related to postural control.

We investigated the modulating effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice treated with urethane. Pulmonary ornithine decarboxylase induction and subsequent polyamine accumulation were observed during the initiation and promotion phases of the urethane-induced lung carcinogenesis in mice. The increases of ODC activity and polyamine level during both phases were almost inhibited when a high vitamin E diet was provided. The urethane-increased level of pulmonary proliferating cell nuclear antigen as a marker of cell proliferation during the carcinogenesis was inhibited by vitamin E treatment. Also, vitamin E suppressed the urethane-induced elevation of pulmonary cyclooxygenase activity as a marker of tumor promotion. In conjugation with these events, vitamin E reduced the development of lung tumors in mice treated with urethane. These results indicated that vitamin E could act as a useful chemopreventive agent against lung carcinogenesis in mice due to the regulation of cell proliferation.

We investigated whether Pyrimidine nucleoside phosphorylase (PyNPase) activity in breast cancer tissue correlated with biological characteristics of breast cancer. PyNPase activity, ER, PgR, EGFR, DNA ploidy pattern, PCNA positive cells and amplification of the c-erbB-2 gene were determined in specimens from 138 patients. PyNPase activity was significantly higher in ER negative than ER positive carcinomas (p<0.05), in PgR negative than PgR positive carcinomas (p<0.05) and significantly higher in tumors with c-erbB-2 gene amplification compared with tumors with no amplification (p<0.05). The results suggest that PyNPase activity in breast cancer tissue may be a new biological characteristic of breast cancer.

A patient with pulmonary pseudolymphoma whose chest X-ray shadows could be observed for over five years is reported. A 73-year-old man was admitted to our hospital in March 1993, because of abnormal shadows on a chest X-ray film. There was a solitary mass in the left upper lung field and infiltrate in the right middle and lower lung fields. These shadows had been observed on a chest X-ray film in 1988, and had been gradually growing for more than five years. Transbronchial lung biopsy (TBLB) of the left upper lobe mass resulted in a histological diagnosis of pulmonary pseudolymphoma. The shadows showed no change during the next nine months after his discharge. These findings are suggestive of the natural history of pulmonary pseudolymphoma. It seems that the process involved in this case was benign rather than malignant.

In order to refine our adjuvant chemotherapy against locally advanced breast cancer, an anticancer drug sensitivity test, using the MTT assay was conducted with biopsy specimens of human breast cancer obtained prior to therapy. Dose-dependent sensitivity was observed with all tested agents: cisplatinum, mitomycin C, methotrexate and doxorubicin. The sensitivity of the premenopausal specimens to the effects of mitomycin C and doxorubicin varied widely. When selecting chemotherapeutic agents to combat breast cancer, this variation in drug sensitivity based on menopausal status and patient age should be considered.

A multi-institutional late phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 26 nationwide hospitals. KW-2307 was intravenously administered at a dose of 20 mg/m2 once weekly. Eighty among the enrolled 82 patients were eligible. The overall response rate was 30.0% (24/80) with 4 CR, 20 PR, 5 MR, 22 NC, 17 PD and 12 unevaluable patients. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included general fatigue, nausea-vomiting, anorexia, paresthesia, fever and stomatitis, but none of them was serious.

Results of 65 cases of small cell lung cancer (SCLC) treated from Jan. 1981 to May 1991 were reviewed. There were 58 male and 7 female patients and their age was ranging from 37 to 86 (mean 65). There were 41 limited disease (LD) and 24 extensive disease (ED) cases. According to TNM (UICC 1987) staging system, there were 2 cases of stage I, 4 of stage II, 9 of stage III A, 28 of stage III B and 22 of stage IV. Among 65 cases, 60 cases received radiotherapy and 55 cases of them received radiotherapy for primary site. There were 29 cases received radiotherapy combined with BAI (bronchial artery infusion) and 20 cases received systemic chemotherapy. On survival, the 2-year survival rate was 26% and MST was 13 months in LD patients (n = 41). No 2-year survivors were seen in ED patients and MST was 10 months. Tumor response of primary site was as follows. In systemic chemotherapy group, CR 35%, PR 59%, NC 6% and PD 0% before radiotherapy and CR 59% after radiotherapy were obtained. In BAI group (including BAI + systemic chemotherapy), CR 6% and PR 88% before radiotherapy in BAI group. BAI did not seem to improve response rate compared to systemic chemotherapy. On survival, BAI group did not show significant better survival compared to BAI (-) group in LD cases (n = 31). In responders (evaluable LD cases, n = 24), the MSTs were 25 months in CR cases and 13 months in PR cases. No 2-year survivors were seen in PR cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative clinical trials among 3 regimens for patients with advanced or recurrent breast cancer were performed as a multi-institutional joint study. Arm-I of 3 regimens consisted of a 3-day consecutive administration of adriamycin (ADM) at 10 mg/body every 4 weeks, a daily oral administration of cyclophosphamide (CPA), 5-FU and tamoxifen (TAM) at 100 mg, 200 mg, and 20 mg, respectively, and a once-a-week intramuscular or subcutaneous injection of OK-432 (OK) gradually increased from the initial dose of 1 KE to the maintenance dose of 5 KE. Arm-II contained methotrexate (MTX) at 10 mg/body for 3 consecutive days every 4 weeks in place of ADM in Arm-I. Arm-III contained neither ADM nor MTX. Of 69 cases registered, 52 were eligible, leaving 6 non-eligible and 11 incomplete cases. The results of the overall evaluation of 48 complete cases other than 4, in which the tumor was not exactly measured, were as follows. Arm-I resulted in 2 CR and 3 PR out of 19 cases, the response rate being 23.6% (5/19). Arm-II resulted in 1 CR out of 15, the response rate being 6.7% (1/15). In Arm-III, no response cases were found. No significant difference was observed among three treatment groups (p = 0.055), but in Arm-I, the response rate was higher than in the other treatment groups, suggesting that there is a probability of useful combined use of ADM.

To investigate the effect of breast self-examination (BSE), we compared the stages, survival, and the risk of death for 355 patients with breast cancer detected by BSE with those for 1,327 patients with breast cancer detected by chance. The early stages of the disease were found to be more common among the symptomatic breast cancer patients detected by BSE than those by chance. The 5-year overall survival rate was 94.4% for the symptomatic patients detected by BSE, and was significantly higher by 8.7% than that (85.7%) for patients detected by chance (P less than 0.001). The 10-year survival rate was 81.6% for patients detected by BSE, and 76.6% for cases detected by chance (the difference was not significant). The overall difference between the two survival curves was statistically significant by the logrank test (P less than 0.01). A multivariate analysis using the Cox proportional hazards model showed that the risk of death for patients detected by BSE was smaller by 0.570 times than that for patients detected by chance, which was statistically significant (P less than 0.05). The effect of biases inherent to BSE in the survival analysis cannot be controlled completely even after conducting multivariate analysis. These results suggest that BSE may contribute to the reduction of the risk of death through early detection of breast cancer. However, further examination should be conducted by other methods to obtain conclusive evidence.

We developed a modified transcatheter arterial infusion method using anticancer agents to treat hepatic malignancies; intermittent injections of iodized oil, lipiodol, containing adriamycin or epirubicin during the arterial infusion of cisplatin (75-200 mg/body) in order to achieve a higher concentration and longer retention of these anticancer agents in the tumor tissue. Fourteen patients with hepatocellular carcinoma (HCC) and five patients with metastatic liver cancer were treated with this "pile-up" arterial infusion therapy by anticancer agents without gelatin sponge TAE. In HCC patients, 50% or greater reduction in tumor size was obtained in 7 of 14 patients (50%). Serum AFP levels decreased by more than 75% in 6 of 7 patients in whom pretreatment serum levels of AFP were more than 200 ng/ml. The one-year and two-year survival rates were estimated at 55% and 27.5%, respectively, by the Kaplan-Meier method. Significant reduction in tumor size was not observed in 5 cases with metastatic liver cancer. Concerning the adverse effects, alimentary symptoms and fever were noted for a few days in many cases, but they were temporary and tolerable in almost all of the patients. Severe adverse changes in laboratory data were not observed. Thus this "pile-up" infusion therapy of anticancer agents without TAE may be a useful therapy for HCC.

Adrenal imaging was performed using magnetic resonance (MR) was in 100 patients who had no clinical or biochemical evidence of adrenal abnormality and in 19 patients with 24 adrenal lesions (adenoma in 5, hyperplasia in 2, metastasis in 5, (lung cancer in 1, hepatoma in 4) adrenal cancer in 1, pheochromocytoma in 3, neuroblastoma in 3). Normal adrenal glands showed intermediate intensity between muscle and liver, and were detected in over 90% of cases on T1-weighted images (T1-weighted SE, inversion recovery). Adenomas and hyperplasias had the same intensity as normal glands. Medullary masses showed extreme hyperintensity on T2-weighted images and could be differentiated from cortical masses. Neuroblastomas were detected as hyperintense tumors with intratumoral hemorrhage and necrosis on T2-weighted MR images. Metastatic adrenal tumors from lung cancer were hyperintense on T2-weighted images, while metastasis from hepatoma showed low intensity on the same pulse sequence. In diagnosing adrenal metastasis, we must compare and contrast the tumor intensity and structure with those of the primary lesions. MR is considered a useful modality in characterizing adrenal tissue.

The total dosage and therapeutic value of Cyclophosphamide (CPA) administered as adjuvant chemotherapy for breast cancer were studied. The subjects were those under 65 years of age who were diagnosed as Stage II breast cancer and underwent curative operation at any of 10 national hospitals from May, 1978 to April, 1981. CPA at dose of 100mg was administered orally every day. Comparison was made between the long-term administration group (L) of patients receiving a total of 25 g/m2 over 18 months and the short-term administration group (S) receiving a total of 6 g/m2 over 6 months, in terms of survival rate (SV) and disease-free survival rate (DFV). Cases selected as the subjects were randomly allotted to the two groups by means of the envelope method. The number of cases registered was 316. Of them, 308 cases were eligible for the study. Thirty-eight cases (23.6%) in L and 15 cases (10.2%) in S dropped out due to side effects and other reasons. No difference was observed between the two groups in background factors such as age, menopausal status, type of operation, histological diameter of tumor, histological type and metastasis to lymph nodes. Results of a 10-year follow-up revealed no difference in SV and DFV between the two groups. Excluding the drop-out cases, however, DFV was significantly high in L. There was no difference in DFV between the two group in terms of menopausal status. DFV was significantly high in L, if one includes cases with metastasis to lymph nodes. DFV was high in L, even when a group with no more than 3 metastatic lymph nodes and the group with not less than 4 were included. It is of little value to administer CPA to all Stage II cases for a long period of time. CPA may be indicated for cases showing metastasis to lymph nodes.

To evaluate the life-prolonging effect of mass screening for breast cancer, we compared the risk of death for the patients detected by mass screening with that for the patients diagnosed in out-patient clinics, after adjusting for other relevant factors simultaneously by using the Cox regression model. A multivariate analysis using the Cox regression model in which clinical staging of disease was taken as one of the independent variables, showed that the risk of death for patients detected by mass screening was smaller by 0.765 times than that for patients found in out-patient clinics although the reduction was not statistically significant. This small reduction might be partly due to the effect of mass screening through early detection even within the same stage, and partly due to length bias, lead time bias and self-selection bias. When clinical staging of disease was removed from the independent variables, the risk of death for patients detected by mass screening was reduced from 0.765 times to 0.677 times that for patients diagnosed in out-patient clinics, which was statistically significant (P greater than 0.01). For asymptomatic patients detected by mass screening, such as reduction of the risk of death was from 0.789 times to 0.555 times that for patients found in out-patient clinics (P less than 0.05). These results suggest that mass screening for breast cancer may contribute to the reduction of the risk of death, although the effect of biases inherent in periodic screening was not removed completely in the present analysis.

In a nation-wide collaborative study on mass screening for breast cancer, we collected 152 cases of interval breast cancer diagnosed at 35 hospitals or clinics distributed throughout Japan. The definition of interval breast cancer used in the present study is "breast cancer cases which were diagnosed as having 'no malignant findings' in a previous screening for breast cancer but subsequently diagnosed as 'breast cancer' at a hospital or medical clinic within two years of the previous screening." The clinical stages and prognoses of these interval cancer were analyzed and compared with those of other breast cancers detected through mass screening and in outpatient clinics. In the clinical staging of interval breast cancer, Tis (non infiltrating cancer) accounted for only 2.1%, compared to 8.0% in cases detected through mass screening. At stage I 43.4% were interval breast cancers compared to 32.9% breast cancers detected through mass screening and 25.4% diagnosed in outpatient clinics. The stage differences between interval breast cancers and breast cancers detected through mass screening were not statistically significant. Five-year survival rates were 85.6% for interval breast cancers, 91.7% for breast cancers detected through mass screening and 84.7% for breast cancers diagnosed in outpatient clinics. Ten-year survival rates were 75.9, 80.5 and 78.1%, respectively, suggesting the interval breast cancer cases to show a similar prognosis to that of breast cancer cases diagnosed in outpatient clinics. The differences in five- and 10-year survival rates among the three groups were not statistically significant. From the present study we were not able to confirm the general belief of interval cancer being more aggressive in nature and showing a poorer prognosis than cancer detected through periodic screening. The reasons for this are discussed.

The property of pluronic F127 (PLF) as a base for an anticancer agent, mitomycin C (MMC) was evaluated. A weighed amount of PLF and MMC were slowly added to cold water and mixed completely. The solution was warmed to 37 degrees C and MMC containing PLF gel was formed. The cumulative amount of MMC which was released from the gel during a 3-hour period was calculated. 5.5 percent of MMC was released from PLF-MMC gel which contained 20 or 25% PLF and 3.8% MMC from PLF-MMC gel containing 30% PLF. Intraperitoneal (i.p.) administration of large amount of PLF gel alone in rabbits or mouse revealed severe hepatorenal toxicity, and acute i.p. administered LD50 of PLF was supposed to be between 1.7 g and 5.0 g/kg body weight in mouse. Further evaluation of gradual releasing property of PLF is needed.

Using a questionnaire, the urinary function of 68 patients and the sexual function of 81 patients were evaluated after rectal cancer operation. The patients with carcinoma of the rectum suffered from severe damage to the urinary system following Miles' operation (Miles) which included 85.7% of the male and 42.9% female. On the other hand, 31.8% male and 33.3% female suffered following anterior resection or pull through operation (AR). Following Miles 64.3% male and 71.4% female had developed urinary incontinence while 36.4% male and 33.3% female developed the same following AR. These results indicate that dysfunction of the urinary voiding system was more common in the males while the females experienced urinary incontinence. This difference may be due to the severity of the surgical intervention to the bladder neck and partly to the anatomical difference of pelvic floor and of urethra. The recovery was poor in the patients who had developed disorder of the urinary voiding system and unfortunately 84% patients following Miles and 75% patients after AR could not return to normal voiding even five years after operation. Urinary incontinence persisted after Miles and after AR in 77.8% and 31% patient respectively. Sexual activity was remarkably reduced following Miles. The males lost the power of erection and ejaculation, the females suffered due to the existence of artificial colostomy. In order to maintain the normal physiological activity of the urogenital system following operation, it is important to avoid any damage preferably to the bladder neck and urethra in case of males and to avoid artificial stoma in females.

To establish the effective mass screening projects for the breast cancer, our study group cosponsered by the Welfare Ministry was organized by 11 regional groups. From 1968 to 1986, 643, 513 women at the initial screening and 719, 189 women at the subsequent screening were examined by physical examination. Out of them, abnormalities were present in 24, 864 women (3.9%) and 23,880 (3.3%), respectively. A detection of cancer was made in 833 women (detection rate 1.3%) and 428 women (0.6%), respectively. As the examinees increased from year to year, the subsequent examinees were over the initial ones. It was suggested that most of examinees had been fixed year by year and the detection rate of initial screening had been higher than that of the subsequent one. Then more initial examinees are expected to be increased. Women 30 to 59 years of age were mostly screened, but women aged 60 or more should be increased. Of women with abnormal physical findings, women over 90% took the second examination. But more effective, economical and safer screening instruments are expected to be developed and be used at the first examination.

Thirty-three anus-preserved rectal cancer patients with anterior resection or low anterior resection were asked about their postoperative defecation conditions with questionnaires after a more than one and half year postoperative period. Beforehand the residual anorectum length was defined by subtracting the length of the specimen AW and 1.5 cm as suturing width from the length of the anal verge through the anal tumor margin during romanoscopic examination. Involuntary soiling frequently occurred in the cases with a less than 9 cm residual anorectum, in the female cases and in the cases associated with lateral lymph node dissection. But these factors have no definite relation to the time of disappearance of involuntary soiling. Half of the cases were normalized in 2 years, and 80% in 3 years. Frequent bowel movement occurred in a high percentage of cases, especially in the cases with short residual anorectum or with lateral lymph node dissection. Frequency of defecation decreased from 8-9/day up to 6 months later, to 5/day up to one year later, and 2-3/day up to 6 years later. Improvement of the above-mentioned condition was slightly delayed in the less than 6 cm residual anorectum group and in females, but not in the lateral lymph node dissection group. Anastomosis insufficiency caused a delay in recovery from involuntary soiling.

Seventy-four breast cancer patients, who had undergone outpatient excisional biopsy followed by radical mastectomy, were divided into three groups according to the types of intramammary cancer residuals: no cancer residuals--45 patients, noninvasive cancer residuals--15, and invasive cancer residuals--14. The invasive cancer residual group included nine patients with axillary metastasis and showed a significantly higher rate of five-year recurrence (8/14) than the other two groups. In some of the patients with invasive cancer residuals, the lesions were more advanced and aggressive by nature. Histopathologically, invasive cancer residuals closely correlated to the nondesmoplastic infiltrating tumor border, and noninvasive cancer residuals to intraductal cancerous spread. Most intramammary cancer residuals were found close to the wounds made by biopsy.

To establish the criteria for assessing the life-prolonging effect of mass screening for breast cancer, clinical stage and prognosis of breast cancer detected by mass screening in 11 regions of Japan were compared with those for matched patients in out-patient clinics. A total of 728 patients detected by mass screening and 1,450 found in the out-patient clinics were reviewed. The stage of the disease was Tis or I in 40.9% of the patients detected by mass screening, and 28.7% of those found in the out-patient clinics. In contrast, stage III was found in 9.3% and 14.6%, respectively, indicating that early stages were significantly more common in the patients detected by mass screening. The overall survival curve for the patients detected by mass screening was compared with that for those found in the out-patient clinics. The 5-year survival rate was significantly higher in the patients detected by mass screening (91.7% vs. 85.6%; P less than 0.01), while the 10-year survival rate was slightly higher in the same group of patients, but the difference from the other group was not significant (80.5% vs. 78.1%). Women who had conducted breast self-examination (BSE) showed a higher survival rate than those who had not conducted BSE.

A new method of plotting the impurity profile is described. It makes efficient use of the advantage of an operational amplifier and the nonlinearity of the junction capacitance in a semiconductor. When two small ac signals are applied to the inverting input terminal of the operational amplifier, intermodulation arises due to the nonlinearity of the junction capacitance inserted in the feedback loop, at the time the reverse bias voltage to the junction can be supplied from the noninverting input terminal; then the signals concerning both the depletion layer width x and the impurity concentration N (x) arise at the output terminal of the operational amplifier. By detecting each of the amplified input signals and the difference-frequency ones corresponding to x and N (x), respectively, the relation of x-N (x) can be plotted easily, at the same time, in a short time, and at a low cost.