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H Akaza

Publications and source records attributed to H Akaza.

At least 37 records · Page 2Linked to original sources

[A case of transitional cell carcinoma of the urinary bladder with high serum level of CEA and CA19-9].

An 85-year-old male with asymptomatic gross hematuria was diagnosed with invasive bladder tumor, transitional cell carcinoma grade 3. Serum levels of CEA and CA19-9 were elevated and histological examination revealed expression of both markers in the cytoplasm of cancer cells. Out of therapeutic options, intra-arterial chemotherapy and radiotherapy were selected because of his age. During the treatment, serum levels of CEA and CA19-9 decreased along with reduction of tumor size. These serum markers have been reported to be elevated in 10 to 60% of patients with bladder tumor and are useful markers for evaluation of the treatment as suggested in the present case.

Aged↗

[Verify the optimum administration of anticancer agent--cisplatin].

Cisplatin shows effectiveness for various solid cancers and often plays a role as the key drug in combination chemotherapy. The most common method of cisplatin administration is bolus intra-venous injection. However, other administration methods are tried in order to reinforce the effect, and also to reduce the side effects. Generally, renal damage is more prominent with bolus injection. In contrast, bone marrow suppression is more severe with intermittent administration. Although there is no clear evidence about the anti-tumor effects, a dramatic local effect is sometimes observed by intra-arterial chemotherapy. By intraperitoneal chemotherapy, while a systemic effect is observed in addition to local effects, due consideration of the systemic side effects is also needed. These protocols are used in many institutes, but the efficacy is not yet proven by comparison trials. In future, randomized prospective studies should be performed to test the usefulness of the regimens.

Antineoplastic Agents↗

[Prostate cancer].

Prostate specific antigen (PSA) has been widely used as a tumor marker for screening, diagnosis and monitoring of prostate cancer. Use of PSA is very important for diagnosis during the primary screening for the early detection of prostate cancer. The presence of various PSA assays and with no uniform serum data have led to confusion among clinicians in the evaluation of serum data. The characteristics of each PSA assay, such as the equimolar or skewed type, must be taken into consideration at the time of use. For the early detection of prostate cancer, PSA density (PSAD), PSA adjusted for the transiton zone volume (PSATZ) and free to total PSA ratio may be useful in the selection of patients with intermediate PSA levels who should undergo prostate needle biopsy.

Adult↗

Antitumor effects of the intravesical instillation of heat killed cells of the Lactobacillus casei strain Shirota on the murine orthotopic bladder tumor MBT-2.

PURPOSE: To characterize the potential of heat killed Lactobacillus casei, Shirota strain (LC9018), as an alternative to bacillus Calmette-Guerin (BCG) for treating patients with bladder cancer we investigated the antitumor effects of intravesical instillation of LC9018 in the MBT-2 orthotopic bladder tumor implantation model in C3H/He mice. MATERIALS AND METHODS: LC9018 or BCG, Tokyo 172 strain, was instilled once daily for 10 days starting on the day after orthotopic implantation of MBT-2. Tumor appearance and mean bladder weight on day 21 after tumor implantation were evaluated. Moreover, we investigated the augmentation of local cellular immunity in bladder mucosa by immunohistochemical staining and reverse transcription polymerase chain reaction. RESULTS: Intravesical LC9018 instillation significantly reduced the rate of tumor appearance in 8 of 38 subjects (p <0.001) and mean tumor growth plus or minus standard deviation with a bladder weight of 37 +/- 49 mg. (p <0.001) compared with tumor appearance in 41 of 58 subjects and mean bladder weight 146 +/- 183 mg. in controls. BCG had no significant antitumor activity in the orthotopic implantation model. Intravesical instillation of LC9018 augmented the local expression of antitumor cytokine messenger RNA (interferon-gamma and tumor necrosis factor-alpha) and induced the infiltration of neutrophils surrounded by macrophages that phagocytosed LC9018 cells at the bladder mucosa. CONCLUSIONS: These results suggest that LC9018 is potentially more potent and safer as a therapeutic agent than BCG for superficial bladder tumors. Furthermore, the antitumor effect of LC9018 is exerted via the augmentation of local cell mediated antitumor immunity.

Administration, Intravesical↗

[Comparison of management of advanced cancer in various organs].

The management of advanced cancer presents the greatest challenge to physicians involved in oncology. There will usually be a large burden of disease; cure is unlikely; and the needs of the patient in terms of pain control and palliation will also be important over and above the direct treatment of the disease. Different issues will arise depending on the site and pathological type of the cancer. Increasingly over the past few years, treatment protocols and guidelines have been developed for different cancers, but these can only be rough guides rather than definite treatment recommendations. Additionally in most cancers advanced disease offers the opportunity for evaluation of new treatments in Phase II studies and other trials. With the new generation of molecular targeted therapies, such as EGFR inhibitors, striking results are being seen in advanced disease that compare favourably with what has been seen previously. Other agents such as those which attack the tumour vasculature may also have promise in this setting. Palliation is also an important aspect of the management of advanced disease, and pain control in particular is an important component of patient management. In summary, the treatment of advanced disease provides a test bed for new agents, but this need to develop better cancer therapies must be balanced against patient needs for a pain-free and comfortable end to life.

Antineoplastic Combined Chemotherapy Protocols↗

[Bladder cancer].

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Age Factors↗

Tissue-engineered artificial urothelium.

Bladder wall replacement is one of the most challenging problems of urologic surgery. Various materials have been tried in experimental models, but most were not free of complications, such as leakage, infection, and stone formation. In addition, much time was needed for tissue regeneration after grafting. Bladder replacement with tissue-engineered materials, which basically consist of autologous cells seeded on a supporting structure, represents an area of rapidly expanding interest. Recently, several investigators have reported important, successful results from in vitro systems and animal models. Here we review those experimental approaches to tissue-engineered artificial urothelium.

Animals↗

Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB).

The objective of this study was to determine the effects of androgen depletion by 5alpha-reductase inhibitor (eg epristeride), pure antiandrogen (eg casodex) or C17-20 lyase inhibitor (eg YM116) on rat prostate carcinogenesis induced by administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB). DMAB was subcutaneously administered on male F344 rats for the first 20 weeks. Epristeride (10 and 50 mg/kg, three times per week), casodex (15 and 30 mg/kg, three times per week) or YM116 (15 and 30 mg/kg, three times per week) were administered orally for 40 consecutive. Then, all accessory sex organs were studied for the formation of neoplastic lesions by histological examination. All carcinoma lesions were produced only in the ventral lobe of the prostate. The incidence of carcinoma developing in the ventral lobe of the prostate was 9.5% in the control group on which DMAB alone was administered, whereas it was 31.6% in the epristeride 10 mg/kg group. 45.0% in the epristeride 50 mg/kg group, 47.8% in the casodex 15 mg/kg group, 63.2% in the casodex 30 mg/kg group, 10.5% in the YM116 15 mg/kg group and 5.0% in the YM116 30 mg/kg group. The incidences of carcinoma in the epristeride 10 mg/kg group, casodex 15 mg/kg group and casodex 30 mg/kg group were significantly higher than that of the control group. In this experimental model, all ventral prostate carcinomas were in situ adenocarcinomas that did not form palpable nodules or distant metastasis. Epristeride and casodex showed a dose-dependent promoting effect on rat ventral prostate carcinogenesis. These results were contradictory to the results of our previous studies; exogenous testosterone in combination with DMAB produced palpable, and metastatic tumors in other portions of accessory sex organs of F344 rats but no carcinoma in ventral prostate, and those invasive carcinomas were significantly inhibited by 5alpha-reductase inhibitor and nonsteroidal anti-androgen. The action mechanisms of androgen and the effects of androgen-regulatory drugs on prostate carcinogenesis should be further studied. Prostate Cancer and Prostatic Diseases (2000) 3, 115-119

Journal Article↗

A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer: a prospective study.

BACKGROUND: A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. METHODS: Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. Intra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. RESULTS: Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. CONCLUSIONS: This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function.

Aged↗

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer.

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.

Adult↗

Ex vivo gene therapy using granulocyte-macrophage colony-stimulating factor-transduced tumor vaccines.

There is no standard effective therapy for metastatic renal-cell carcinoma (RCC) or prostate cancer. Both of these cancers may be immunogenic, so therapy targeted to a tumor-associated antigen may be effective. Transduction of the gene encoding granulocyte-macrophage colony-stimulating factor has shown promise in preclinical studies, and clinical trials are in their early stages. Both autologous cancer cells and partially HLA-matched allogenic cells are being studied. No dose-limiting side effects have been observed, and a few patients have had transient objective tumor regressions. Further trials with more frequent and, probably, longer immunization schedules are needed to define efficacy.

Animals↗

Screening for prostate cancer using prostate-specific antigen alone as a first-line checkup parameter: results of the health checkup system.

BACKGROUND: The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. METHODS: Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. RESULTS: Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. CONCLUSIONS: These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.

Aged↗

Early results of LH-RH agonist treatment with or without chlormadinone acetate for hormone therapy of naive localized or locally advanced prostate cancer: a prospective and randomized study. The Prostate Cancer Study Group.

BACKGROUND: The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients. METHODS: A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostate-specific antigen level, progression-free survival and survival were observed for 2 years. RESULTS: The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient's wish (32%) and physician's recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later (p<0.05). Group II showed a longer progression-free survival (p <0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer. CONCLUSIONS: Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years' observation.

Aged↗

Advances in chemotherapy of invasive bladder cancer.

A survey of the literature published during 1999 identified the following advances in the chemotherapy of advanced bladder cancer. At present there are no new chemotherapy regimens superior to MTX + VBL + ADR + CDDP (M-VAC), but improvements in multidrug therapies and the development of new drugs suggest that a new first-line chemotherapy will be established. The efficacy of neoadjuvant chemotherapy could not be validated by meta-analysis, but neoadjuvant chemotherapy can be expected to be a useful tool for individualizing therapy. If it was possible to select accurately those patients who show complete response to a certain chemotherapy regimen, then this selected group would show a 100% complete response rate on that regimen, regardless of the complete response rate of this regimen in an unselected population. Such individualization of therapy would aid in future establishment of bladder-preserving treatment methods for invasive bladder cancers.

Antineoplastic Combined Chemotherapy Protocols↗

Alterations in expression of cadherin-6 and E-cadherin during kidney development and in renal cell carcinoma.

OBJECTIVES: Cell-cell adhesion mediated by cadherins is tight and stable and preserves tissue integrity. However, during tissue remodeling, e.g., development, adhesion may be modified for morphogenic movement. Similarly, during carcinogenesis, cell-cell adhesion might alter leading to a more aggressive phenotype. Here we describe cadherin expression patterns in developing, adult, and neoplastic kidney. METHODS: Fetal kidneys were obtained from voluntary terminations of pregnancy and 43 renal cell carcinomas (RCC) and normal kidneys were obtained at nephrectomy. Frozen sections of these specimens were stained immunohistochemically using antibodies against E-cadherin (ECD), cadherin-6 (CAD6) and alpha-catenin (alpha-cat). RESULTS: CAD6 was expressed in lower and middle limbs of the S-shaped bodies, structures that will develop into renal proximal tubules, which also express CAD6. Similarly, ECD was expressed in the upper limb of S-shaped bodies, structures which will develop into distal and collecting tubules which also express ECD. Twenty-four out of 43 RCC (55.8%) displayed a CAD6 (+)/ECD (-)/alpha-cat (+) phenotype. The other RCC had a CAD6 (+)/ECD (+)/alpha-cat (+) phenotype (10/43, 23.2%), CAD6 (-)/ECD (+)/alpha-cat (+) phenotype (3/43, 7.0%) or CAD6 (-)/ECD (-)/alpha-cat (+) phenotype (6/43, 14.0%), respectively. On the other hand, normal, heterogeneous, or absent expression of CAD6 was seen in 19, 15, and 9 tumors, whereas in 11, 2, and 30 tumors, respectively, ECD expression was seen. Survival curves showed that abnormal CAD6 expression correlated with a poor prognosis rather than abnormal ECD expression. CONCLUSIONS: The combination of cadherin expression appeared to be fixed relatively early during kidney organogenesis. Since almost all RCC originate from proximal tubular epithelial cells (CAD6 (+)/ECD (-)/alpha-cat (+)), only 55. 8% of RCC retained the original cadherin phenotype. Alterations in expression of these molecules may be a reflection of the degree of dedifferentiation from the primary organ. In addition, scoring of expression patterns including heterogeneous expression could be a useful tool to estimate the malignancy potential of the tumor.

Cadherins↗

[Intrascrotal tumors: a clinicopathologic study of 15 cases].

PURPOSE: We reviewed cases of intrascrotal tumors treated at our institution except for germ cell testicular tumors. PATIENTS AND METHODS: From 1977 to 1998 (22 years), 120 cases of intrascrotal tumors treated at the University of Tsukuba. Of these, 15 cases (12.5%) were not germ cell testicular tumors. The patients' ages varied between 2 and 77 years with a mean of 49.6. RESULTS: The most common complaint regarding symptoms was painless testicular enlargement. Tumor weight ranged from 2 to 200 g, with an average of 104.6 g. The histological diagnoses of 15 patients were 8 malignant lymphomas, 2 paratesticular rhabdomyosarcomas, 2 metastatic tumors (origin; stomach and prostate), 1 epidermoid cyst, 1 cyst of tunica testis, and 1 adenomatoid tumor. As for the cases with malignant lymphoma, all of them were non-Hodgkin's lymphoma whose clinical stages were stage I in 2 cases and stage IV in 6 cases. Five 8 patients died in spite of systemic chemotherapy after an orchiectomy, whereas 2 cases with metastatic tumors died of primary cancer, and two cases with paratesticular rhabdomyosarcoma are still alive and have had no evidence of disease. CONCLUSIONS: Intrascrotal tumors except for germ cell testicular tumors are not common, and consist of various diseases. In particular, some kinds of malignant lymphoma mimic anaplastic seminoma histopathologically. Therefore, accurate diagnosis and precise treatment is important in the patient with intrascrotal tumors.

Adolescent↗

[Evidence-based medicine for urological cancer chemotherapy].

We reviewed the treatment results of urological cancer chemotherapy from the standpoint of evidence based medicine. In the treatment of advanced transitional cell carcinoma of the urothelium, M-VAC (MTX + VBL + ADM + CDDP) is regarded as the standard regimen; however, durable event-free survival is rare. There is no level 1 evidence to date showing that the use of neoadjuvant or adjuvant cisplatin-based regimens will improve survival in cases of locally advanced bladder cancer. Immunotherapy with interferon or interleukin-2 produces a small survival advantage in patients with metastatic renal cell carcinoma. There is no evidence that adjuvant interferon-alpha administration will improve the survival in those with non-metastatic renal cell carcinoma. Systematized cisplatin-based treatment protocols have been established in patients with advanced testicular germ cell tumor by means of many randomized controlled trials. Several clinical trials are under way to prove the efficacy of high dose chemotherapy (with autologous stem-cell support) in patients with poor risk germ cell tumors. We do not yet have sufficient data to conclude whether maximal androgen blockade will prolong the survival in patients with metastatic prostate cancer, nor to conclude whether neoadjuvant androgen depletion treatment improve disease free survival of the patients after radical prostatectomy.

Carcinoma, Transitional Cell↗

[New combination chemotherapy in urological cancers].

Although several effective therapeutic modalities are currently available for each urological cancer, there are still many patients for whom cure is not possible. Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are both standard agents for patients with metastatic renal cell carcinoma (RCC). However, only up to 20% of patients can attain a complete response with these agents. It has been reported that for bladder transitional cell carcinoma (TCC), a cisplatin-based chemotherapy such as M-VAC chemotherapy can give patients a prognostic benefit in an adjuvant setting. There has been no therapy to improve upon M-VAC for more than a decade. In this review, several trials with new combination chemotherapies that were developed to overcome the limitations of the current therapy are discussed. These include the combination of IL-2, IFN-alpha and 5-fluorouracil for RCC, paclitaxel/gemcitabine and cisplatin/carboplatin for TCC, and paclitaxel/docetaxel and estramustine for hormone-refractory prostate cancer. The results of initial trials with these new combination therapies are promising. Large scale clinical trials, however, have yet to be done.

Antineoplastic Combined Chemotherapy Protocols↗