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Biomedical subjects

K Akakura

Publications and source records attributed to K Akakura.

At least 19 recordsLinked to original sources
PubMed2003

Treatment and prognosis of patients with paraplegia or quadriplegia because of metastatic spinal cord compression in prostate cancer.

Metastatic spinal cord compression (MSCC) is a serious complication of metastatic prostate cancer (PCa). This study retrospectively evaluated patients who presented with paraplegia or quadriplegia because of MSCC of PCa. Of 847 patients with PCa who were treated between 1989 and 1998, 26 (3.1%) demonstrated paraplegia or quadriplegia because of MSCC. Characteristics, treatment efficacy, and prognosis of these patients were analyzed. In total, 15 cases became paraplegic despite androgen ablation therapy (Group I). Average time to paraplegia from initial hormonal treatment was 34 months. Out of nine cases who underwent radiation therapy (RT) to spinal lesions with/without chemotherapy, one patient became ambulatory. However, this patient subsequently had recurrent compression. Two cases had remission of paralysis. Two cases underwent laminectomy plus RT and in one case paralysis improved. MSCC was the first indication of PCa in 11 cases (Group II). Two cases underwent laminectomy plus hormone therapy and nine cases underwent hormone therapy alone. Four patients became ambulatory and two cases showed improved motor capacity. Average interval from paraplegia to death was 7.4 months in Group I and 27.1 months in Group II. However, there was no statistical difference in these two groups on disease-specific survival from the start of initial treatment. It is difficult to recover the ability to walk if paraplegia or quadriplegia occurs in PCa patients although decompression surgery plus hormone therapy seemed to impair the prognosis. Stage M1 patients with paraplegia had survival rates as good as stage M1 patients without paralysis. This should encourage an aggressive treatment approach. However, for patients with hormone-independent disease there seems to be no effective treatment and prognosis is poor.

Adenocarcinoma↗
PubMed2002

Clinical significance of pulmonary metastases in stage D2 prostate cancer patients.

Several prognostic factors such as the extent of bone metastases (EOD) in advanced prostate cancer (PCa) have been reported. Metastasis of the lung is rarely a significant clinical factor in the management of prostate cancer. The present study evaluates the clinical significance of lung metastases. We retrospectively reviewed the PCa database to identify patients with pulmonary metastases at initial diagnosis. The medical records of the patients were examined with respect to age, histologic grade, EOD score, marker response to endocrine therapy and clinical outcome. We then compared several potential clinical factors between patients with and without pulmonary metastases. Next, we retrospectively reviewed autopsy records of 60 Japanese patients who died of hormone-refractory metastatic PCa with particular focus upon metastatic profiles. A comparative study of stage D(2) patients with (n=20) and without (n=77) pulmonary metastases found no significant differences in EOD score, performance status, marker response and survival. Only tumor grade was better in the group with, than without pulmonary metastases (P=0.0120, chi-square analysis). In the series of autopsies, we found pulmonary metastases in 38 cases (63%), following metastases of the bone (57 cases, 95%) and lymph nodes (52 cases, 87%). A retrospective analysis of survival showed that patients with bone or lymph node metastases had a positive relative risk. In contrast, lung metastasis could be a positive prognostic indicator, although the findings were not statistically significant. These data suggest that the presence of pulmonary metastasis has no ominous impact on clinical course and disease outcome even in patients with disseminated prostate cancer.

Aged↗
PubMed2001

Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer.

BACKGROUND: CD44 is a metastasis suppressor gene for prostate cancer and the down-regulation of CD44 and its variants is associated with the progression of prostate cancer. Also, hypermethylation of the CpG islands of the CD44 gene is closely associated with transcriptional inactivation, resulting in the decreased expression of CD44. To clarify the exact role of methylation status of CpG islands of CD44 gene in the progression and metastasis of prostate cancer, we investigated the methylation status of this gene in primary and metastatic human prostate tumors obtained from surgery or autopsy. METHODS: We examined 97 samples from 40 Japanese patients with adenocarcinoma of the prostate. Tumor tissues were obtained from radical prostatectomy specimens from eight patients with stage B, 12 patients with stage C and three patients with stage D1 and at autopsy from 17 hormone-refractory metastatic cases, who had initially responded to the therapy and thereafter relapsed. Distant metastatic tissues were also obtained at autopsy (i.e., liver, lung, kidney, mammary gland, and pelvic lymph nodes) from 10 of 17 hormone-refractory cases. We analyzed the hypermethylation status of CD44 promotor region by PCR using genomic DNAs digested with the m(5)C-sensitive restriction enzyme HpaII. RESULTS: The correlation between the methylation status of CD44 gene and the stage progression of prostate cancer was statistically significant (P = 0.0438). In two of 10 hormone-refractory cases, a comparison of the methylation status of the CD44 gene in metastases to that in primary tumors revealed interfocal heterogeneity of CD44 methylation status. CONCLUSIONS: These results indicate an important role of CD44 methylation in the progression and metastasis of prostate cancer, although the amount of methylational heterogeneity is substantial among metastatic sites within the same patient.

Adenocarcinoma↗
PubMed2001

Prognostic significance of changes in prostate-specific antigen in patients with metastasis prostate cancer after endocrine treatment.

Patients with metastatic prostate cancer respond to androgen withdrawal therapy, but progression to androgen independence is frequently observed. To clarify the predictor of response to endocrine therapy, the role of PSA changes and the prognosis of the patients were evaluated in 115 Japanese cases of prostate cancer with distant metastases treated with androgen withdrawal therapy. When patients were divided according to the pretreatment PSA value (high, > or = 500, median; 500 > PSA > or = 100, low; 100 >), patients whose initial PSA levels were high had a worse cause-specific survival. PSA value at 3 or 6 months following endocrine treatment, PSA nadir, and percent decrease of PSA were associated with prolonged survival. Clinical relapse was observed in 68 patients. Patients with distant recurrence had shorter time to PSA elevation than those with local recurrence. In metastatic prostate cancer patients treated with androgen withdrawal, serial measurement of PSA could distinguish nonfavorable responders early in the course of treatment and assist in monitoring for disease progression.

Aged↗
PubMed2001

Assessment of renal function with color Doppler ultrasound in autosomal dominant polycystic kidney disease.

BACKGROUND: Measurement of renal blood flow by color Doppler ultrasound is useful for assessment of renal function in a variety of renal disorders. In autosomal dominant polycystic kidney disease (ADPKD), however, it might be difficult to visualize interlobar arteries because of deformity of renal structure. To evaluate the usefulness of color Doppler in ADPKD, parameters determined by blood flow examination were compared with the results of ordinal renal function tests. METHODS: Twenty-one patients with ADPKD were examined by color Doppler ultrasound measurement. In each patient, 10 interlobar arteries in both kidneys were investigated. Minimum blood flow velocity (Vmin), maximum blood flow velocity (Vmax), mean blood flow velocity (Vmean), acceleration, resistive index and pulsatility index were measured in relation to the results of creatinine clearance, serum creatinine, blood urea nitrogen and 15 and 120 min values of the phenolsulfonphthalein test. RESULTS: In all patients, interlobar arteries were able to be visualized and blood-flow profile was measured. Although variations of Vmin, Vmax, Vmean and acceleration were relatively large, the resistive index and pulsatility index varied little in each kidney. Mean values of Vmin (P < 0.005), Vmean (P < 0.05), resistive index (P < 0.005) and pulsatility index (P < 0.005) were well correlated to creatinine clearance with statistical significance. CONCLUSIONS: In ADPKD, color Doppler ultrasound measurement is a useful method for assessment of renal function and could be used for monitoring the dynamic state of renal blood flow as a non-invasive technique.

Aged↗
PubMed2001

Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer.

BACKGROUND: Long-term results were analyzed to evaluate the role of endocrine therapy in the management of local and distant recurrence of prostate cancer following external radiation therapy. METHODS: Between 1976 and 1994, 92 patients with untreated prostate cancer underwent external beam radiation therapy alone. Endocrine therapy had been started when relapse was evident. RESULTS: Failure was seen in 35 of 92 patients: 10 local, 19 distant and six biochemical failures. Endocrine treatment was performed in 28 patients with nine local and 19 distant failures. The cancer-specific survival rate from the endocrine treatment was 54.5% at 5 years. Prostate-specific antigen level in 20 of 20 patients (100%) decreased to below the normal limit 3 months after the start of endocrine therapy. In univariate analysis, T classification was the most significant variable for cancer-specific survival from the initial treatment. CONCLUSIONS: A favorable outcome was achieved by endocrine therapy in patients who had relapsed after external beam radiation monotherapy. Even the recurrent tumor had a sensitivity to androgen. Patients with locally advanced disease (T2b and T3) had poorer prognosis than those with minimally extended disease (T1b and T2a).

Aged↗
PubMed2001

Prostate adenocarcinoma producing syndrome of inappropriate secretion of antidiuretic hormone.

The syndrome of inappropriate secretion of antidiuretic hormone (ADH) was recognized in a 68-year-old man with a poorly differentiated metastatic adenocarcinoma of the prostate. Elevated levels of ADH were found in the tissues of the primary tumor and lymph node metastasis. The patient's clinical course is detailed and the pathophysiology of this syndrome is discussed. To our knowledge, this case is the ninth reported case of syndrome of inappropriate secretion of ADH with adenocarcinoma of the prostate. Antidiuretic hormone activity was proven in only three cases including this case.

Adenocarcinoma↗
PubMed2001

Human cystinuria-related transporter: localization and functional characterization.

BACKGROUND: Cystinuria has been proposed to be an inherited defect of apical membrane transport systems for cystine and basic amino acids in renal proximal tubules. Although the mutations of the recently identified transporter BAT1/b(0,+)AT have been related to nontype I cystinuria, the function and localization of human BAT1 (hBAT1)/b(0,+)AT have not been well characterized. METHODS: The cDNA encoding hBAT1 was isolated from human kidney. Fluorescence in situ hybridization was performed to map the hBAT1 gene on human chromosomes. Tissue distribution and localization of expression were examined by Northern blot and immunohistochemical analyses. hBAT1 cDNA was transfected to COS-7 cells with rBAT cDNA, and the uptake and efflux of 14C-labeled amino acids were measured to determine the functional properties. The roles of protein kinase-dependent phosphorylation were investigated using inhibitors or activators of protein kinases. RESULTS: The hBAT1 gene was mapped to 19q12-13.1 on the human chromosome, which is the locus of nontype I cystinuria. hBAT1 message was expressed predominantly in kidney. hBAT1 protein was localized in the apical membrane of proximal tubules in human kidney. When expressed in COS-7 cells with a type II membrane glycoprotein rBAT (related to b(0,+)-amino acid transporter), hBAT1 exhibited the transport activity with the properties of amino acid transport system b(0,+), which transported cystine as well as basic and neutral amino acids presumably via a substrate exchange mechanism. BAT1-mediated transport was reduced by the protein kinase A activator and enhanced by the tyrosine kinase inhibitor. CONCLUSIONS: hBAT1 exhibited the properties expected for a transporter subserving the high-affinity cystine transport system in renal proximal tubules. The hBAT1 gene was mapped to the locus of nontype I cystinuria, confirming the involvement of hBAT1 in cystinuria.

ATP-Binding Cassette Transporters↗
PubMed2001

Serum immunosuppressive acidic protein as a potent prognostic factor for patients with metastatic renal cell carcinoma.

BACKGROUND: Estimation of survival probability of individual patients with metastatic renal cell carcinoma was difficult owing to diverse prognostic factors. We analyzed serum immunosuppressive acidic protein (IAP) levels and the cutoff value, then tested its validity for assessing patients' prognoses. METHODS: Serum IAP was measured longitudinally in 84 patients with metastatic disease. Before therapy, cutoff levels of IAP were tested every 20 microg/ml between 600 and 1200 microg/ml. The prognostic importance of IAP and its cutoff level was estimated. RESULTS: The cutoff level of IAP was set at 800 microg/ml for 40 patients who had metastatic disease with the primary tumor in situ and for 44 patients with recurrent disease. IAP was found to be a significant prognostic factor for both patient groups. CONCLUSIONS: Serum IAP is an important prognostic factor for patients with metastatic renal cell carcinoma. Stratification of patients according to prognosis is feasible using the cutoff level.

Adult↗
PubMed2001

Epigenetic regulation of the KAI1 metastasis suppressor gene in human prostate cancer cell lines.

Expression of the KAI1 gene, a metastasis-suppressor for prostate cancer, is reduced in all foci of prostatic metastasis. The altered regulatory mechanism is not strongly related to mutations or allelic losses of the KAI1 gene in prostate tumors. Since transcriptional silencing of genes has been found to be caused by epigenetic mechanisms, we have investigated the involvement of this epigenetic regulation of KAI1 expression in prostate cancers. The methylation status of the KAI1 promoter region was examined by restriction-enzyme digestion and sequencing, after amplifying a 331-bp fragment in the GC-rich promoter region from 4 human prostate cancer cell lines treated with bisulfite. The same 4 cell lines were also exposed to various concentrations of the demethylating agent, 5-aza-2'-deoxycytidine (5-AzaC) and / or the histone deacetylase inhibitor, trichostatin A (TSA). To clarify the influence of epigenetic modification on reduced KAI1 mRNA expression in the tumor cells, RT-PCR and northern-blot analyses were performed. Bisulfite-sequencing data showed a few methylated CpG islands in the promoter. RT-PCR analysis of 5-AzaC and / or TSA-treated cells indicated reversal of suppression of KAI1 transcription in two cell lines (PC-3 and DU-145), although the expression could not be detected by northern blots. From these results, it is suggested that epigenetic change is not the main mechanism of KAI1 down-regulation, though there remains a possibility that methylation in a more upstream region might be associated with this regulation.

Adenocarcinoma↗
PubMed2001

Pretreatment serum level of testosterone as a prognostic factor in Japanese men with hormonally treated stage D2 prostate cancer.

Pretreatment serum level of testosterone (T) is a potential prognostic factor for prostate cancer. However, T levels in Japanese prostate cancer patients are unknown to date. To evaluate the clinical significance of pretreatment serum T level in such patients, serum T level was analyzed in relation to several clinical factors in a total of 130 patients with various stages of prostate cancer, 74 of whom had metastatic disease (stage D2) and received endocrine therapy as first-line treatment. The mean pretreatment T level in patients with non-metastatic prostate cancer (stages B + C) was significantly lower than that in stage D2 patients (B + C: 4.05 +/- 2.01 ng/ml; D2: 4.85 +/- 2.18 ng/ml, p = 0.0344). On the other hand, the mean serum level of T was higher in stage D2 patients who showed good response to endocrine therapy (CR: 5.42 +/- 1.55 ng/ml; non-CR: 4.30 +/- 2.63 ng/ml, p = 0.0320). When the 74 stage D2 patients were divided into high and low T level groups according to the median value, those patients with a high T level had significantly better cause-specific and progression-free survival. Multivariate analysis demonstrated that extent of bone metastases (EOD) grade, pretreatment serum T level and tumor marker response to endocrine therapy were significant predictors for progression-free survival. In conclusion, a higher pretreatment T level appears to be predictive of the marker response to endocrine therapy, showing positive prognostic value and indicating good prognosis in patients at the metastatic stage. However, a higher T level was also associated with stage progression of this disease.

Aged↗
PubMed2000

Laparoscopic adrenalectomy for functioning adrenal tumors: clinical experiences with 38 cases and comparison with open adrenalectomy.

We reviewed 38 cases of transperitoneal or retroperitoneal laparoscopic adrenalectomy for unilateral benign functioning adrenal tumors and compared the results with those of a recent series of 36 patients undergoing an open adrenalectomy. The tumors were removed successfully in all but two cases with laparoscopy that required open laparotomy. In the other 36 cases of the laparoscopy group, mean operative time and blood loss were 225 minutes and 138 mL, respectively. Mean operative time was significantly longer for the laparoscopy group (122 minutes for open surgery: P < 0.0001), whereas mean blood loss of the laparoscopy group was almost equal to that of the open surgery group. Mean intervals to first ambulation and oral intake, and postoperative hospital stay of the laparoscopy group were significantly less than those of the open surgery group (1.4 vs 2.0 days: P = 0.014; 1.8 vs 2.9 days: P < 0.0001; and 8.5 vs 12.9 days: P < 0.0001, respectively). We conclude that laparoscopic adrenalectomy is equally effective and less invasive than open adrenalectomy. and that it should be considered as the first-choice therapy for benign adrenal tumors.

Adrenal Gland Neoplasms↗
PubMed2000

Effect of prostatic biopsy on free-to-total prostate-specific antigen ratio in patients with prostate cancer.

BACKGROUND: We determined the effect of prostatic biopsy on the changes in total and free prostate-specific antigen (PSA) and free-to-total PSA ratio (F/T ratio) and examined if there are differences in these parameters between patients with benign and malignant histologic findings. METHODS: The concentration of total and free PSA and the F/T ratio were determined in 35 men before and 1 h after prostatic biopsy. The level of PSA was measured with a chemiluminescent enzyme assay. Of 35 patients, nine were diagnosed as having prostate cancer. RESULTS: In patients whose biopsy revealed cancer, the F/T ratio was lower than those without cancer, although there were no differences in total and free PSA value before prostatic biopsy. One hour after prostatic biopsy, there was an increase in the level of total and free PSA and the F/T ratio in all men. The increase in the F/T ratio was greater in patients whose biopsies revealed no prostate cancer. In patients with stage B cancer, these parameters increased more than those with stage C/D cancer. CONCLUSION: Prostatic biopsy causes a dramatic increase in total and free PSA. The F/T ratio also increased after biopsy. The PSA response to prostatic biopsy might be different in patients with and without prostatic malignancy. The response might also be different according to stage of prostate cancer.

Aged↗
PubMed2000

Changes in serum prostate-specific antigen following prostatectomy in patients with benign prostate hyperplasia.

PURPOSE: To investigate how prostatectomy for patients with benign prostate hyperplasia (BPH) affected the serum prostate-specific antigen (PSA) levels. METHODS: In 193 patients who underwent prostatectomy for BPH, serum PSA levels were measured before and three months after the operation. The total prostate weight measured by transrectal ultrasonography (TRUS) and the weight of the surgical specimen were examined in relation to the pretreatment PSA value and the changes in PSA levels after the operation. RESULTS: The transition zone volume measured by TRUS could well estimate the weight of the surgical specimen in patients who underwent subcapsular prostatectomy and transurethral resection of the prostate. The concentration of preoperative serum PSA showed a significant correlation with the prostatic volume and with the transition zone volume. Removal of 1 g of BPH tissue reduced serum PSA levels by an average of 0.18 ng/mL. The change in serum PSA levels after the prostatectomy correlated with the total prostatic gland volume and with the transition zone volume. CONCLUSIONS: The elevated PSA levels in patients with BPH were caused by the enlargement of the transition zone. After the resection of the adenoma, PSA levels should be expected to decrease to the normal range.

Adenoma↗
PubMed2000

Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria.

UNLABELLED: Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria. BACKGROUND: Cystinuria is an inheritable amino aciduria and has been classified into three subtypes: I, II, and III. One of the genes responsible for cystinuria has recently been identified as SLC3A1 or rBAT, but only type I cystinuria seems to be caused by genetic alterations in rBAT. To our knowledge, thus far 38 mutations in rBAT gene have been described. In this study, we investigated rBAT mutations in Japanese patients and compared the results with the previously reported mutations in other races. METHODS: We investigated 36 Japanese cystinuria patients by mutational analysis of rBAT gene. To identify newly mutated alleles, genomic DNA was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). When an abnormal migration was observed on SSCP, a nucleotide sequence determination was performed. RESULTS: Five novel mutations were identified in five patients, three with missense mutations (L346P, I445T, C673R), one with a 1 bp deletion (1820delT), and one with a 2 bp insertion (1898insTA), and we detected three previously reported polymorphisms. Three of the mutations were homozygous, in whom parents had intermarried, and two were heterozygous for each mutations. Analysis of rBAT in family of the 1898insTA patient revealed that the patient had inherited the mutated allele from his parents. CONCLUSION: Five novel mutations in the rBAT gene have been identified in Japanese patients with cystinuria. A racial difference was not apparent in the position and frequency of the mutations.

Amino Acid Transport Systems, Basic↗
PubMed2000

Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men.

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.

Aged↗