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Biomedical subjects

Hideyuki Akaza

Publications and source records attributed to Hideyuki Akaza.

At least 109 records · Page 6Linked to original sources
PubMed2002

Testicular cancers occurring in brothers with cryptorchism.

We report a case of familial testicular cancer associated with undescended testes in two brothers. The older brother (49 years) presented with a testicular tumor located in the right inguinal canal. The pathologic diagnosis was pure seminoma. Computerized tomography revealed iliac and retroperitoneal lymph node metastases. Four years later, the younger brother (44 years) developed bilateral testicular tumors, one located in the inguinal canal, the other located in the pelvic cavity. The pathologic diagnosis of both tumors was pure seminoma. Radiological examination revealed retroperitoneal lymph node metastases. Both patients received cisplatin-based combination chemotherapy as the initial treatment. The older brother suffered from repeated recurrences with lymph node metastases in the iliac and inguinal regions, but he was successfully treated with high-dose chemotherapy. The younger brother achieved long-term remission after retroperitoneal lymph node dissection following initial chemotherapy. We briefly review the reported cases of familial testicular cancer and discuss the association of the maldescent of the testes and familial testicular cancer cases.

Adult↗
PubMed2002

Immunological protection induced by bacillus Calmette-Guérin treatment in a murine bladder tumor model.

BACKGROUND: It has been previously reported that MBT-2 tumor growth is completely inhibited when mice are inoculated with bacillus Calmette-Guérin (BCG). In this study it was examined whether or not vaccination with a mixture of BCG and MBT-2 cells also induces immunological protection against murine bladder tumors. METHODS: Seven hundred thousand MBT-2 cells and 1 mg of BCG (Tokyo 172 strain) per mouse were injected subcutaneously into female C3H/HeN mice. Four and eight weeks after vaccination with this mixture, animals were reinoculated with MBT-2 cells alone or MBT-2 cells cocultured with BCG. RESULTS: Animals vaccinated with a mixture of BCG and MBT-2 cells showed MBT-2 tumor growth but completely rejected the MBT-2 cells cocultured with BCG. MBT-2 cells cocultured with BCG developed into tumors when they were inoculated into the control animals. Splenocytes prepared from vaccinated animals showed specific cytocidal activity against MBT-2 cells precultured with BCG. CONCLUSIONS: The results suggest that a mixture of BCG and MBT-2 cells induces antitumor immunological protection against BCG- or MBT-2-associated antigens presented on MBT-2 cells precultured with BCG.

Animals↗
PubMed2002

Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: a clinical course of the first Japanese experience.

A phase I study of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor vaccine for patients with metastatic renal cell carcinoma (RCC) was initiated in 1998, as the first cancer gene therapy in Japan. The study is still ongoing, but the first patient is presented here as a case report. The patient was a 60-year-old man with Stage IV CRC with multiple lung metastases. After surgical resection of the tumor, autologous tumor cells were transduced and cultured to produce GM-CSF. The patient received a total of 2.2 x 108 gene-transduced autologous vaccine cells by subcutaneous injection. During the course of vaccination, growth of the largest metastatic mass slowed to some extent; however, multiple new lesions developed. About 1 month after the start of low-dose IL-2 therapy, rapid and remarkable regression in a large lung hilar metastatic mass was noticed. The patient died of progressive disease 7 months after the start of GM-CSF gene therapy. Careful histological examination by autopsy revealed that the responding mass was infiltrated by CD8 positive dominant T lymphocytes, and did not exhibit vasculitis or any other changes associated with active autoimmune disease.

Carcinoma, Renal Cell↗
PubMed2002

Clinical study of varicocele: statistical analysis and the results of long-term follow-up.

BACKGROUND: The results of clinical examinations of varicocele and the clinical outcome of varicocelectomy conducted at Tsukuba University Hospital, Tsukuba City, Japan were analyzed. METHODS: The subjects of the present study were sixty-four infertile male patients with varicocele who visited our hospital from 1991 to 1999. A physical examination, semen analysis and hormonal evaluation were performed for each patient. Patients selected their preferred type of treatment (varicocelectomy or conservative treatment) after providing their informed consent. RESULTS: The age of the patients was 34.1 +/- 5.1(mean +/- standard deviation [s.d.]) years, and the infertile duration was 4.2 +/- 3.0 (mean +/- s.d.) years. Fifty-one cases were left-sided; 13 were bilateral. Mean sperm density ( yen 106/mL) was 37.2 for Grade I, 21.3 for Grade II and 9.4 for Grade III. Sperm density was significantly lower in the higher-graded patients (P = 0.008). Varicocelectomy was performed in 31 cases; the postoperative/preoperative ratio of sperm density was significantly higher in the higher-graded varicocele (P = 0.04), and the peak/base ratio of follicle-stimulating hormone (FSH) after luteinizing hormone-releasing hormone (LH-RH) stimulation was significantly decreased after varicocelectomy (P = 0.007). The pregnancy rate in the partners of the varicocelectomized group (60%) was significantly higher than in the conservatively treated group (28%) P = 0.04; the mean follow-up duration was 76.2 months. CONCLUSION: These results show that varicocele should influence spermatogenesis, therefore altered spermatogenesis could be effectively treated by varicocelectomy, and varicocelectomy should induce a higher probability of pregnancy.

Adult↗
PubMed2002

The Influence of handling censored data on estimating progression-free survival in cancer clinical trials (JCOG9913-A).

BACKGROUND: Progression-free survival (PFS) is a common endpoint in cancer clinical trials. This study was undertaken to assess the impact of data errors and data handling on the statistical estimation of PFS. METHODS: Data from four trials conducted by the Japan Clinical Oncology Group were examined. Three types of data handling methods were defined: (1) data handling method A (METHOD-A), the collected event data are used as much as possible, (2) METHOD-C, only reliable data with firm evidence are used, and (3) METHOD-B is intermediate between METHOD-A and METHOD-C. To assess the impact of each of the three methods, Kaplan-Meier survival curves, median PFS, proportion of PFS, log-rank p values and hazard ratios were estimated. RESULTS: In three trials that collected PFS data periodically, no remarkable differences in median PFS and the proportion of PFS were observed. In one trial with non-periodic data cleaning, however, the ratio of median PFS by METHOD-C to that by METHOD-B was 0.85, the maximum difference of proportion of PFS between METHOD-C and METHOD-B was 12.0% and the largest spread in PFS curves amongst the three methods was observed in this trial. In all trials, log-rank p values and hazard ratios for between arm comparisons did not differ between the three methods. CONCLUSIONS: Periodic data management can reduce errors in comparisons of PFS and is a critical requirement when using PFS as a major endpoint. Furthermore, proper data handling is essential in the estimation of patient benefit and caution is needed when making clinical decisions based on PFS.

Clinical Trials as Topic↗
PubMed2002

Is daidzein non-metabolizer a high risk for prostate cancer? A case-controlled study of serum soybean isoflavone concentration.

BACKGROUND: It has been postulated that soybean isoflavones act as inhibitory factors in prostate cancer. However, to date there have been no case-controlled clinical studies carried out to compare the circulating concentrations of isoflavones in prostate cancer patients and control subjects. METHODS: The serum levels of genistein, daidzein and equol were determined and compared in 253 experimental subjects (141 prostate cancer patients and 112 cancer-free controls). RESULTS: The serum concentrations of isoflavones were compared in hospitalized and non-hospitalized subjects and for both the prostate cancer patients and the controls the concentrations were lower in the hospitalized subjects. The serum concentrations of genistein and daidzein were compared in subjects <70 years of age and subjects >/=70 years old and the levels were significantly lower in the younger group. Contrary to our expectation, comparison of the patient group and the control group revealed the serum concentrations of isoflavones to be higher in the patient group. Daidzein non-metabolizers were compared in the hospitalized experimental subjects of the patient group and the control group and they were significantly more common in the patient group. The poorly differentiated cancer patient group included a significantly lower percentage of daidzein metabolizers. CONCLUSIONS: The above findings revealed that equol itself or some unknown factor regulating the metabolism of daidzein is deeply involved in the biology of prostate cancer. Future studies are urgently needed to compare the incidence of daidzein metabolizers among various countries.

Aged↗
PubMed2002

Telomerase is upregulated in irreversible preneoplastic lesions during bladder carcinogenesis in rats.

Multiple occurrence or recurrence after transurethral resection is an important characteristic of superficial bladder tumors. To study bladder carcinogenesis, we focused on detection of telomerase activation, which was investigated in several human cancers, including bladder tumors. We experimentally examined the telomerase activity during bladder carcinogenesis, especially in precancerous lesions, induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. Male Wistar rats were given 0.05% BBN in water from the age of 8 weeks to 24 weeks. Subgroups were euthanized at 4, 8, 10, 12, 18, and 24 weeks after BBN administration. Using the stretch PCR method, telomerase activity was semiquantified in exfoliated bladder epithelial cells. In addition, telomere length in each subgroup was measured by southern hybridization for the terminal restriction fragment using a (TTAGGG)(4) probe. Statistical analyses were performed using analysis of variance and Fisher's PLSD test. Epithelial cells of normal bladder in the control groups and those of diffuse hyperplasia, which was a reversible change at 4 weeks, expressed no telomerase activity. In contrast, telomerase activity significantly increased in the stage after nodular hyperplasia, an irreversible change at 8 weeks, then elevated with carcinogenesis. However, telomere length was still preserved by the 12th week, and was shortened at 18 and 24 weeks. These results suggest that telomerase activation is probably induced independent of telomere shortening during bladder carcinogenesis in the rat, and might be a biological tumor marker of irreversible preneoplastic lesions, which evolve into bladder tumors in the rat.

Animals↗
PubMed2002

Habitual intake of lactic acid bacteria and risk reduction of bladder cancer.

INTRODUCTION: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. METHODS: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). RESULTS: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively. CONCLUSION: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.

Aged↗
PubMed2002

Developing therapies for advanced bladder cancer.

Chemotherapy is an indispensable measure in the treatment of invasive or metastatic bladder cancer as even if metastases are not clinically apparent, the majority of cases of invasive bladder cancer are accompanied by micrometastases. At present, MVAC (methotrexate, vinblastine, adriamycin, cisplatin) is the gold standard for bladder cancer chemotherapy. There have consequently been many attempts at MVAC dose-intensification as well as many studies of the feasibility of neoadjuvant chemotherapy using MVAC. Unfortunately, the majority of results from these studies have been negative or contradictory. However, a recent large-scale randomised, controlled study yielded more promising results. Evidence has recently emerged which indicates that a useful chemotherapeutic strategy could possibly be devised by adjusting the dose and timing of MVAC. Increasing effort is also being put into the development of new gold standards for bladder cancer chemotherapy based on the use of newly developed antitumour drugs, and a number of candidates have emerged. It is hoped that the future we will see successful establishment of a number of useful regimens as a result of Phase III clinical studies using MVAC as their control regimen. For example, both gemcitabine and the taxanes, in combination with other drugs, are strong candidates for this purpose. The ultimate therapeutic strategy for bladder cancer will be a therapeutic approach which permits conservation of the bladder even when the malignancy is invasive and steady progress is already being made toward this goal, in limited cases, by means of multidisciplinary treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Intravesical instillation of doxorubicin or epirubicin for chemoprophylaxis of superficial bladder cancer--the fifth study of the Japanese Urological Cancer Research Group for Adriamycin/Farumorubicin].

A total of 465 patients with primary and multiple or recurrent, stages Ta and T1 superficial bladder cancer were included in this randomized multicenter trial to compare the prophylactic effect by 17 times instillation of 40 mg doxorubicin or 40 mg epirubicin with no instillation after transurethral resection of tumor(s). The primary endpoint was first recurrence after transurethral resection. Endoscopic examination as well as urinary cytology was performed in each case every three months. It became evident that the recurrence rate in the doxorubicin or epirubicin instillation arm was lower that in the no instillation arm. Toxicity was mainly restricted to bladder irritation in about 10% of patients in each instillation arm.

Administration, Intravesical↗
PubMed2002

[Globalization of anti-cancer therapies].

Based on short reviews of lung, gastric, colorectal, prostate, breast and ovarian cancer, there remain significant differences between Japan and the West in the therapeutic regimen for most cancers. Some of the differences are due to differences in stage of disease at diagnosis or historical factors affecting availability of products. In both Japan and the West, there are initiatives to prepare treatment guidelines based on published data. For Japan this initiative is limited by the lack of Japanese clinical trial data or even safety data. When guidelines are prepared from international data, many of the products have limited indications in Japan and therefore not reimbursed. Availability of the most appropriate therapies to Japanese patients will depend on a facilitation of clinical trials in both primary and additional indications. However, the experience in other countries is that, even where data and registration approval are available, guidelines are hard to agree and are not uniformly accepted by prescribers. The ICH E5 guideline on the use of bridging studies to interpolate Western data to Japanese regulatory dossiers provides an opportunity to accelerate availability of new medicines to Japanese prescribers and patients. The use of bridging studies has so far been limited for anti-cancer therapies. Where relevant pharmacodynamic endpoints can be measured, (e.g. aromatase inhibition) there can increase confidence in bridging. The newer types of agent which act to stabilise disease rather than tumour shrinkage present a special problem. In some cases surrogate markers can be valuable but in each case they need to be validated. As globalization continues, an alternative approach is to include a significant cohort of Japanese patients in Japanese patients but this depends on sufficient similarity in the patient population and background therapy. The most significant limitation to either large outcome studies in Japan or for Japanese centers to join international trials has been the environment for conduct of clinical trials. There have been some recent improvements and further progress is expected so that Japanese doctors can play a full role in the evaluation of new therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Chemotherapy and radiotherapy for urological cancer].

Prostate cancer, bladder cancer, renal cancer and testicular cancer are common among urological cancers. The treatment strategy for testicular cancer using chemotherapy has been well established and has been shown to be successful. Chemotherapy and radiotherapy play important roles in multidisciplinary therapy for bladder cancer. Radiotherapy is often used as a radical treatment that is practically equivalent to surgery for prostate cancer. In addition, radiotherapy is useful in cases of bone or brain metastases. In the field of chemotherapy, the development of new agents that would make breakthroughs similar to that of cisplatin is awaited. Taxanes and gemcitabine are good candidates. In the field of radiotherapy, 3D conformal radiation therapy (CRT), which has excellent beam distribution, has recently come into wide use. Moreover, brachytherapy and proton and ion beam therapy are expected to prove useful in prostate cancer therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Saphenous vein grafting for Peyronie's disease: a case report].

We present a case of Peyronie's disease in a 50-year-old male with a progressive, painful induration (3 x 2 x 0.5 cm) in the dorsal region of the penis. In order to correct the high degree of penile curvature, we made a venous patch graft from the saphenous vein under general anesthesia and straightened the penis. Six months after the operation, a recurrent induration was observed in the proximal region of the penis, and the penis became slightly shortened.

Humans↗
PubMed2002

[The significance of assessment of quality of life as a cancer treatment].

Now that cancer treatments have advanced and people are surviving longer, considerations of patient QOL are becoming more important. QOL questionnaires are lists of questions taken from more than two domains. The questions are roughly divided into the "general scale" type, which asks people, patients or not, about their level of general QOL, and the "disease specific scale" type, which investigates the level of QOL focusing on the effects of the disease or treatments. Questionnaires of QOL specific to patients suffering from cancer has the former as core questions, with the latter added for type of cancer, treatments, and symptoms. Two questionnaires, EORTC QLQ and FACT, are most often used in clinical research, and Japanese versions are also available. When investigating the change in the level of the QOL with time, the disease specific scale, which better reflects changes due to the disease, is useful. Moreover, using a questionnaire that is easy to complete will minimize deficit values, and raise the accuracy of data. Use of sample questionnaires available on the Internet will be useful in preliminary surveys. Any medical treatment has a detrimental effect on patients' mind and body. We hope that the results of the QOL research are utilized as evidence in deciding which medical treatments to give patients.

Anxiety↗
PubMed2002

[Urology].

We reviewed comparative clinical studies for prostate cancer and bladder cancer performed in Japan. A systematic search was done using PubMed and Icyushi WEB to find randomized clinical trials and the result was verified. Each manuscript was summarized according to the seven items of stage, entry period, exposure, endpoint, sample size, method of randomization and result. Forty reports were found as randomized clinical trials for prostate cancer, and sixty-two reports were identified for bladder cancer. Most exposures for advanced prostate cancer were hormonal therapy involving intravesical instillation after transurethral resection for superficial bladder cancer. At minimum, we have clarified that large scale randomized trials have been conducted in Japan for both prostate cancer and bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Meta-analysis and evidence based medicine].

Meta-analysis is a statistical method for combining the results of available research studies to increase statistical power. The steps of meta-analysis are identification of question, search and selection of trials and analysis. Evidence based medicine (EBM) is integrating individual clinical expertise with the best available external clinical evidence from systematic research. The practice of EBM consists of formulated clinical question, systematic review, critical appraisal, application for patients and performance review. We must notice the results of meta-analysis and evidence are keeping up to date. We should use them with critical appraisal skill and should not criticize without good understanding.

Evidence-Based Medicine↗
PubMed2002

Asian trends in prostate cancer hormone therapy.

The first Conference on Asian Trends in Prostate Cancer Hormone Therapy was held in September 2001 to serve as a forum for Asian urologists to compare data on prostate cancer and discuss issues regarding the use of hormone therapy. The conference revealed that due to various cultural and philosophical factors, differences exist in prostate cancer management among the Asian countries. In addition, a lack of databases on hormone therapy was exposed in some countries. It was noted that many decisions in the treatment of prostate cancer are influenced by the strategies adopted in Western countries, and that attempts to formulate uniform guidelines for the Asian region have hitherto been unsuccessful. The main findings of the conference are reported in this review.

Androgen Antagonists↗