Long-term clinical impact of serum albumin in coronary artery disease patients with preserved renal function.

BACKGROUND AND AIMS: Low serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function. METHODS AND RESULTS: We studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan-Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12-3.55), 1.77 (95% CI, 0.99-3.25), and 1.19 (95% CI, 0.68-2.15) for serum albumin concentrations of <3.9, 3.9-4.0, and 4.1-4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37-3.56, p = 0.001). CONCLUSION: Decreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function.

Are Self-Reported Masticatory Ability and Regular Dental Care Related to Mortality?

AIM: The aim of the study was to examine whether a combination of self-reported masticatory ability and regular dental care is linked to mortality and issuance of new long-term care insurance (LTCI) service certifications. METHODS: Older residents in institutions or in need of LTCI certification requirements were excluded, and self-administered questionnaires were sent to 5,400 older adults in 2013; these participants were followed for 5 years. The total response rate was 94.3%, and our final sample comprised 4,824 older adults (89.3%). We used 3 items to assess self-reported masticatory ability and regular dental care. These included (1) decline in chewing abilities of the posterior teeth on either side, (2) not brushing one's own teeth or dentures at least once a day, and (3) not visiting the dentist at least once a year. RESULTS: The mean age of the participants at baseline was 75.9 years, and 58.4% of them were women. Main outcomes included mortality (n = 562) or new LTCI certification requirements (n = 1187) during the 5-year period. Multivariate analyses revealed that a poor score on masticatory ability and on regular dental care produced significant adverse health outcomes leading to earlier negative outcomes. The score is considered poor as it increases relative to the 0-point reference. DISCUSSION: Regular dental care (both self-and professional care) and maintaining masticatory ability are both important. Hence, public activities focusing on preventive oral health from middle age onward is important.

Uracil-tegafur and tamoxifen vs cyclophosphamide, methotrexate, fluorouracil, and tamoxifen in post-operative adjuvant therapy for stage I, II, or IIIA lymph node-positive breast cancer: a comparative study.

BACKGROUND: It has been reported that treatment with uracil-tegafur (UFT) has shown significantly better survival and relapse-free survival (RFS) than surgery alone. Therefore, we compared UFT with a combination therapy of cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients who had undergone curative surgery for axillary lymph node-positive breast cancer. METHODS: A total of 377 node-positive patients with stage I, II, or IIIA disease were registered from September 1996 through July 2000 and were randomly assigned to either 6 cycles of CMF or 2 years of UFT. In both arms, tamoxifen (TAM) was concurrently administered for 2 years. The primary end point in this study was the non-inferiority of UFT to CMF. RESULTS: No statistically significant difference between the two groups was observed with regard to the 5-year RFS rate (72.2% in the UFT and 76.3% in the CMF). Adverse event profiles differed between the two groups, with a significantly lower incidence of leukopenia and anaemia in the UFT group, as well as anorexia, nausea/vomiting, stomatitis, and alopecia, which have implications for quality of life. CONCLUSION: UFT administered in combination with TAM holds promise in the treatment of lymph node-positive early breast cancer. On stratified analysis, the recurrence rate in the UFT group was found to be better in oestrogen receptor (ER)-positive patients. Tegafur-based treatment should be evaluated by a prospective randomised trial conducted in ER-positive patients.

Self-Reported Cognitive Frailty Predicts Adverse Health Outcomes for Community-Dwelling Older Adults Based on an Analysis of Sex and Age.

OBJECTIVES: The present study examined whether the combination of self-reported mobility decline (SR-MD) and cognitive decline (SR-CD) was associated with mortality and new long-term care insurance (LTCI) service certifications based on sex and age. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: We analyzed cohort data from a sample of older adult residents in Kami Town, Japan. The response rate was 94.3%, and we followed 5,094 older adults for 3 years. Full analyses were conducted on 5,076 participants. MEASURES: A total of four groups were determined through self-reported responses on the Kihon Checklist for SR-MD (a score of 3 or more on 5 items) and SR-CD (a score of 1 or more on 3 items): non-SR-cognitive frailty, non-SR-MD and SR-CD, SR-MD and non-SR-CD, and SR-cognitive frailty. RESULTS: Main outcomes included mortality (n = 262) or new certifications for LTCI services (n = 708) during the 3-year period. Excluding overlapping, this included 845 older adults (16.6%). Among men, prevalence of non-SR-cognitive frailty, non-SR-MD and SR-CD, SR-MD and non-SR-CD, and SR-cognitive frailty (SR-MD and SR-CD) was 48.2%, 26.4%, 11.5%, and 13.8%, respectively. Respective rates for women were 45.7%, 15.5%, 23.1%, and 15.7%. Multivariate analyses revealed that for men, SR-MD and non-SR-CD significantly affected adverse health outcomes, leading to earlier negative outcomes relative to the non-SR-MD and SR-CD group. For women, non-SR-MD and SR-CD and SR-MD and non-SR-CD had similar slopes. CONCLUSIONS: The impact of SR-MD or SR-CD on adverse health outcomes differed as a function of age and sex. Thus, we need to consider preventive approaches according to these specific target group features.

Multicentric Castleman disease with secondary AA renal amyloidosis, nephrotic syndrome and chronic renal failure, remission after high-dose melphalan and autologous stem cell transplantation.

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.

Neuropathic Pain Features in Patients with Bone Metastases.

AIMS: The results of previous randomised controlled trials suggest that radiation oncologists should consider the presence of neuropathic pain when they prescribe dose fractionations for painful bone metastases. Although validated screening tools for neuropathic pain features are currently available, the prevalence of such features among patients with painful bone metastases is still poorly understood. The purpose of this study was to estimate the prevalence of neuropathic pain features among patients who received palliative radiotherapy for painful bone metastases. MATERIALS AND METHODS: We conducted a cohort survey of consecutive patients who received palliative radiotherapy for painful bone metastases at St Luke's International Hospital between 2013 and 2014. Patients were prospectively assessed before radiotherapy using the validated screening questionnaire to identify neuropathic pain components in Japanese patients. Pain with neuropathic features was prospectively defined using the total score of the seven-item questionnaire and a cut-off score ≥9. The pain response was assessed 2 months after the start of radiotherapy according to the criteria defined by the International Bone Metastases Consensus Working Party. RESULTS: Eighty-seven patients were assessed. Twenty-four per cent of patients (95% confidence interval: 16-35%) were diagnosed as having pain with neuropathic features. On multivariate analysis, no significant correlations were seen between neuropathic pain features and patient characteristics. Sixty-four patients (74%) were assessable 2 months after the start of radiotherapy. Overall response rates were 59% (95% confidence interval: 33-82%) in patients with neuropathic features and 55% (95% confidence interval: 40-70%) in those without such features. CONCLUSIONS: A considerable proportion of the patients were proven to have bone pain with neuropathic features. Further investigations are warranted to validate symptom assessment tools in cooperation with pain distribution and image findings, and to clarify if the presence of neuropathic pain affects the response to palliative radiotherapy.

The inhibitory effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice.

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.

Pyrimidine nucleoside phosphorylase-activity and biological characteristics of breast-cancer.

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.

Different chemosensitivity of pre and postmenopausal breast-cancer cells.

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.

UFT and mitomycin plus tamoxifen for stage II, ER-positive breast cancer. Hokkaido ACETBC Study Group.

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.

Intratumoral pyrimidine nucleoside phosphorylase (PyNPase) activity predicts a selective effect of adjuvant 5'-deoxy-5-fluorouridine (5'DFUR) on breast cancer.

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.

Two-frequency method for measuring impurity profiles.

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.

A case of pulmonary pseudolymphoma: five years' roentgenographic observation.

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.

Comparison of postural control of children with Down syndrome and those with other forms of mental retardation.

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.

[Transarterial "pile-up" infusion therapy of cisplatin and lipiodol emulsion in hepatic malignancies without TAE (transcatheter arterial embolization)].

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.

[Combination chemotherapy with vinorelbine and other cytotoxic agents for advanced breast cancer patients--a protocol of vinorelbine plus AC regimens used by the Japan Vinorelbin Study Group].

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.

[Evaluation of pluronic F127 as a base for gradual release of anticancer drug].

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.

[Combination therapy with low dose adriamycin for advanced or recurrent breast cancer. Hokkaido Breast Cancer Treatment Study Group].

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.

[Adjuvant chemotherapy using cyclophosphamide for breast cancer. National Hospital Collaborative Group for Study of Breast Cancer Treatment].

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.

[Late phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section)].

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.