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K Akakura

Publications and source records attributed to K Akakura.

At least 55 records · Page 3Linked to original sources
PubMed1998

Response of prostate-specific antigen after androgen withdrawal and prognosis in men with metastatic prostate cancer.

OBJECTIVE: Patients with prostate cancer generally respond to androgen withdrawal therapy, but progression to androgen independence is frequently observed. To evaluate prognostic factors in metastatic prostate cancer, patients who had been treated with endocrine therapy were investigated. METHODS: One hundred and thirty-nine patients with untreated metastatic prostate cancer (TxNxM1) who received endocrine therapy between 1986 and 1993 were included in the present study. Blood chemistry, histological grade, extent of bony metastases, clinical response to hormone therapy, and the prognosis of the patients were evaluated. RESULTS: With univariate analysis, performance status, hemoglobin concentration, serum alkaline phosphatase, lactate dehydrogenase, histological grade, extent of bony disease, and response of prostate-specific antigen (PSA) at 3 months were shown to be significant prognostic factors. With multivariate analyses, response of PSA and histological grade were significant factors predicting prognosis. CONCLUSIONS: Patients whose PSA had not normalized 3 months after the start of endocrine therapy were in the high-risk group, and should be given more aggressive treatment.

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PubMed1998

Prognosis of patients with prostate carcinoma presenting as nonregional lymph node metastases.

OBJECTIVE: The mode of progression in patients with prostate cancer with metastasis to nonregional lymph nodes was examined in order to know whether the site of metastasis effects the prognosis of prostate cancer. METHODS: From 1986 to 1995 at the Chiba University Hospital, 205 cases of prostatic cancer with distant metastases were experienced. In 17 of them, nonregional lymph node metastases were observed at the diagnosis, of whom 10 also had bone metastases. RESULTS: There was no statistical difference in prognosis between 17 patients with nonregional lymph node metastases and remaining 188 patients with metastatic prostate cancer. In all patients metastasized to nonregional lymph nodes, serum prostate-specific antigen and/or prostatic acid phosphatase levels were elevated. Anti-androgen therapy was effective in 15 cases and 5-year survival rate was 45.8%. Patients without bone metastases at the initial diagnosis could survive longer than those with metastases to bone (p < 0.05). CONCLUSIONS: From these observations, endocrine therapy was effective even in patients with distant lymph node metastases.

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PubMed1998

The long-term outcome of cystinuria in Japan.

Recurrence of growth of urinary stone is frequently observed during the clinical course of cystinuria patients. The aim of the present study is to examine the long-term outcome of cystinuria in Japan and clarify the effects of medical treatment on urinary stone. Thirty-one patients with cystinuria who had been followed up longer than 6 months were included. The follow-up period was 6-264 months with a mean of 89.5 months. Stone event was defined as appearance of new stone or radiological evidence of stone growth. All patients were managed with forced hydration and urine alkalization. Twenty-eight patients were treated with administration of thiol such as D-penicillamine or alpha-mercaptopropionylglycine. Stone events per year ranged from 0 to 1.09 with a median of 0.09. Stone events per patient-year was 0.19 for all patients. The average urinary cystine concentration during treatment in the favorable outcome group (stone events per year < 0.3) was lower that that in the unfavorable outcome group (stone events per year >/=0.3); 221.2 +/- 75.2 vs. 303.3 +/- 93.5 mg/l, although the difference was not statistically significant. Prognosis of urinary stone in Japanese patients with cystinuria was relatively good with large variation. The medical treatment to reduce urinary cystine concentration would be useful for the management of cystinuria.

Adult↗
PubMed1998

Comparison of markers of bone formation and resorption in prostate cancer patients to predict bone metastasis.

We investigated the usefulness of two biochemical markers of bone formation (PICP, the carboxy-terminal propeptide of type I procollagen, and bone ALP, bone-derived alkaline phosphatase) and a marker of bone resorption (ICTP, the carboxy-terminal telopeptide of type I collagen), to determine whether the presence of bone metastasis in prostate cancer could be evaluated and the extent of bone metastasis could be stratified by the serum levels of these markers, compared to total alkaline phosphatase (T-ALP) and prostate-specific antigen (PSA). The serum levels of PICP, bone ALP, ICTP, T-ALP and PSA were significantly higher in patients with both prostate cancer and bone metastasis (n=49) than in patients with benign prostatic hyperplasia (n=35) and patients with prostate cancer without bone metastasis (n=70). The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic curves. The serum marker levels were compared as a function of metastatic burden in bone (i.e., the extent of disease, EOD grade). We found that bone ALP is the most suitable marker for evaluating bone metastasis, especially for stratifying the degree of bone metastasis. Both PICP and ICTP were useful in this respect, but rather inferior to bone ALP. T-ALP had the lowest ability for detecting bone metastasis, but its correlation with the EOD grade was excellent, second to that of bone ALP. PSA showed limited reliability for stratifying the extent of bone metastasis.

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PubMed1998

[Carcinoma of the prostate presenting as non-regional superficial lymph node metastasis].

BACKGROUND: The objective of this study is to evaluate the prognosis of carcinoma of the prostate presenting as non-regional superficial lymphnode metastasis. METHODS: From 1986 to 1996 at the Chiba University Hospital, 205 cases of prostatic cancer with distant metastasis were experienced. RESULTS: In nine of them, non-regional lymphnode metastasis was observed at the diagnosis. In all of them, serum prostate specific antigen and/or prostate acid phosphatase levels were elevated. In eight of nine cases, cancer nodule was detected by digital rectal examination. Anti-androgen therapy was effective in eight cases and five year survival rate was 56%. CONCLUSION: From these observations, prostate cancer should be considered when superficial lymphnode was enlarged.

Adenocarcinoma↗
PubMed1998

[Steroidal and nonsteroidal antiandrogens: chemical structures, mechanisms of action and clinical applications].

Antiandrogens are defined as substances which prevent androgens from expressing their activity at target sites. Based on their chemical structures, antiandrogens are divided into steroidal and nonsteroidal antiandrogens. In addition to antiandrogenic action, steroidal antiandrogens simulate the negative feedback inhibition of the hypothalamus, resulting in lowering the concentration of plasma testosterone. On the other hand, in nonsteroidal antiandrogens, the androgenic actions are blocked in both hypothalamus and target tissues. Therefore, negative feedback signals are inhibited and production of testosterone is increased in the testis. For the endocrine therapy of prostate cancer, chlormadinone acetate, flutamide and bicalutamide are or will be available in Japan. Antiandrogen is generally used by the combination with surgical or medical castration, namely as total androgen blockade.

Androgen Antagonists↗
PubMed1998

[Radiation therapy with neoadjuvant hormonal therapy for prostate cancer confined to pelvis].

Neoadjuvant endocrine treatment prior to radical prostatectomy for prostate cancer confined to pelvis has of some value to prevent progression although there are many controversies. In order to improve the prognosis of locally advanced prostate cancer (stage B2 and C), definitive radiotherapy with neoadjuvant endocrine therapy has been investigated. Endocrine therapy reduces the volume of prostate, thus reduces the amount of side effect via reducing the area of irradiated normal tissue. Effect of radiation and that of endocrine therapy to induce apoptosis might be synergistic. The result is favorable although the follow-up period is too short. Further studies are needed to make conclusion.

Gonadotropin-Releasing Hormone↗
PubMed1997

Prognostic factors in patients with prostate cancer refractory to endocrine therapy: univariate and multivariate analyses including doubling times of prostate-specific antigen and prostatic acid phosphatase.

Although several prognostic factors have been discussed, multivariate analysis that includes tumor marker doubling time has not yet been examined in patients with prostate cancer refractory to endocrine therapy. A number of conventional prognostic factors including doubling times of prostate-specific antigen and/or prostatic acid phosphatase were examined in 56 prostate cancer patients who were refractory to endocrine therapy, using univariate and multivariate analyses. On univariate analysis, 6 parameters (doubling times of prostate-specific antigen and prostatic acid phosphatase at the time of refractory status, performance status, duration from beginning of endocrine therapy to prostate-specific antigen/prostatic acid phosphatase failure, mode of recurrence, the presence or absence of prostate-specific antigen/prostatic acid phosphatase normalization, and alkaline phosphatase) were shown to be significant prognostic factors. On multivariate analysis, only performance status and doubling times of prostate-specific antigen and prostatic acid phosphatase were significant. These observations showed that the doubling times of prostate-specific antigen and prostatic acid phosphatase, calculated at the time of prostate-specific antigen/prostatic acid phosphatase failure by estimating serial prostate-specific antigen or prostatic acid phosphatase, were a valuable prognostic factor in patients with prostate cancer refractory to endocrine therapy.

Acid Phosphatase↗
PubMed1997

Prostate-specific antigen levels from a mass screening program using highly sensitive RIA kits.

BACKGROUND: This study was designed to evaluate the distribution of prostate-specific antigen (PSA) levels of men in a mass screening program for prostatic disease. METHODS: A total of 763 men over 40 years of age underwent mass screening for prostatic disease in a Japanese prefecture using the highly sensitive Eiken kit and the Hybritech (Tandem-R) kit. The screening tests consisted of serum PSA determination, digital rectal examination, a questionnaire on symptoms, evaluation of prostate volume, and determination of the obesity rate. RESULTS: Serum PSA levels of all subjects were measured with both kits. The correlation between the values obtained by the Eiken kit and those of the Tandem-R kit was high (r = 0.990), but the values of the former were slightly higher than those of the latter. Serum PSA weakly correlated with age, however, when estimated within decade age brackets, the levels of PSA showed significant differences among only 1 pair of groups stratified by age. In contrast, the levels of PSA showed significant differences among 9 pairs of groups stratified by prostate volume. CONCLUSION: A highly sensitive assay kit is useful to evaluate both the distribution of PSA levels and the relationship of PSA values to age and prostate volume of men in mass screening programs for prostatic disease, since approximately 40% of the subjects who underwent the present mass screening showed PSA values under 1.0 ng/mL, which have been the the lower limit of detection of many PSA kits.

Adult↗
PubMed1997

Relationship between prostate-specific antigen, clinical stage, and degree of bone metastasis in patients with prostate cancer: comparison with prostatic acid phosphatase and alkaline phosphatase.

BACKGROUND: The study was designed to examine the relation of the levels of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) to clinical stage and bone metastasis in prostate cancer patients. METHODS: Serum PSA, PAP, and ALP levels were evaluated in 272 patients with prostate cancer. The relation of the level of PSA, PAP, and ALP to clinical stage and to degree of bone metastasis were examined by a multiple comparison method using ranks. The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic (ROC) curves. The correlation coefficients of the order of the extent of bone metastasis with PSA, PAP, and ALP were examined with Spearman's rank order correlation coefficient test. RESULTS: The levels of PSA showed significant differences among 8 pairs of clinical stages. In contrast, the levels of PAP showed significant differences among 6 pairs, and the levels of ALP showed significant differences among only 4 pairs. The area under the ROC curves of PSA, PAP, and ALP for revealing bone metastasis was 84.9%, 81.4%, and 77.3%, respectively. The correlation coefficients of the order of extent of disease (EOD) with log (PSA), log (PAP), and log (ALP) were 0.346, 0.394, and 0.618, respectively, and the levels of ALP showed the most significant differences regarding the extent of bone metastasis. CONCLUSION: PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.

Acid Phosphatase↗
PubMed1997

Influence of osteoarthritis on serum marker levels of bone formation and resorption in patients with benign prostatic hypertrophy.

BACKGROUND: The aim of this study was to investigate the influence of osteoarthritis of lumbar vertebrae on serum bone formation and resorption marker levels of patients with benign prostatic hypertrophy (BPH). METHODS: Serum levels of carboxyterminal propeptide of type I procollagen (PICP), alkaline phosphatase (ALP), carboxyterminal telopeptide of type I collagen (ICTP), and prostate-specific antigen (PSA) were examined in 40 patients with BPH, and the presence of osteoarthritis at the lumbar vertebrae of the patients was evaluated by plain x-ray-p. RESULTS: Findings of osteoarthritis were observed in 23 of the 40 patients (58%), and 10 of the patients had severe osteoarthritis (involving at least 2 lumbar vertebral bodies). The serum levels of PICP, ALP, ICTP, and PSA of the patients without osteoarthritis findings were not different from those of the patients with osteoarthritis or severe osteoarthritis. CONCLUSION: The influence of osteoarthritis on serum bone formation and resorption marker levels of patients with BPH appears to be rather slight, if there is any influence at all.

Aged↗
PubMed1997

[Mechanism on androgen-independent progression of prostate cancer].

Eighty percent of prostate cancer with metastasis respond to androgen ablasion, showing initial androgen-sensitive growth. However, more than half of responders gradually loses dependency up to 5 years. Animal experiments reveal that loss of androgen sensitivity is attributable to complex reasons; adaptation, paracrine control by other androgen-independent tissues, genetic changes and mutation of androgen receptor. Most important event is explained from alteration of expression on oncogenes and suppressor genes. Counterplan of the progression was discussed.

Androgen Antagonists↗
PubMed1997

[Androgen receptor].

Explore the source record for details and available documents.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

[Prostate cancer].

Up to stage B1 or prostate cancer with N0-1 positive lymph node may be curable by monotherapy of either radical prostatectomy or irradiation. Localized but more advanced stages (B2 and C), however, are difficult to cure. To further improve the prognosis in these stages, a new treatment modality is proposed; pelvic lymphadenectomy, followed by irradiation with neoadjuvant and adjuvant endocrine therapy. An average 2-year followup is favorable. Further studies is awaited to make conclusion.

Androgen Antagonists↗
PubMed1996

Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma.

BACKGROUND: Patients with prostate carcinoma generally respond to androgen withdrawal therapy, but subsequent progression to androgen-independence is frequently observed. Since androgen receptors play a key role in androgen action, the ratio of androgen receptor-containing cells in cancerous tissues was determined by immunohistochemical staining of prostate biopsy specimens for comparison with the outcome. METHODS: Sixty-two patients with untreated Stage D2 prostate carcinoma who received endocrine therapy between 1986 and 1992 were included in the present study. Biopsy tissue was stained with anti-human androgen receptor antibody, and the ratio of positively stained cells was estimated by counting 700 to 1000 cancer cells from each patient. Histologic grade, extent of bone metastases, clinical response to endocrine therapy, and outcome, were compared with androgen receptor content. RESULTS: Cancers with a low Gleason score had a significantly higher androgen receptor content than those with a high Gleason score. Androgen receptor content was not significantly correlated with extent of disease or tumor marker response at three months. Patients with 48% or more androgen receptor positive cells had a statistically significant better outcome, in terms of both progression free and cause-specific survival, than patients with less than 48% androgen receptor content. Multivariate analysis demonstrated that androgen receptor content, extent of disease and tumor marker response at three months were significant predictors of outcome. CONCLUSIONS: Androgen receptor content measured immunohistochemically is a useful prognostic indicator for patients with Stage D2 prostate carcinoma treated with endocrine therapy.

Aged↗
PubMed1996

Codon 877 mutation in the androgen receptor gene in advanced prostate cancer: relation to antiandrogen withdrawal syndrome.

The growth of prostate cancer is androgen responsive, and androgen receptor (AR) is thought to play an important role in the development of this cancer. Recently, some reports demonstrated that AR gene mutations were detected in human prostate cancer tissues. We have previously reported that one of eight endocrine therapy-resistant prostate cancer cases showed AR gene mutation [Suzuki et al: J Steroid Biochem Mol Biol 46:759-765, 1993]. To further investigate structural abnormality of the AR in a large number of human prostate cancers, exons B-H encoding DNA-and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products and direct sequencing. Tissues surgically removed from 30 cases of stage B or C prostate cancer and from 22 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Three out of 22 cancer death cases (14%) revealed AR gene mutations, one of which contained two different mutations-exon D in cancerous prostate and exon H in metastatic tissues. In the other two cases, AR gene mutations in exon H were found in metastatic tissues. All three cases in metastatic tissues showed the same mutation at codon 877 (877Thr-->Ala). In stage B or C cancer tissues and the other cancer death samples, no AR mutation was detected. The mutation in exon H was identical to that reported in a human prostate cancer cell line, LNCaP. These results indicate that AR gene mutation scarcely occurs in the early stage of prostate cancer and that the mutation is found in relation to endocrine therapy resistance. Two patients with an AR gene mutation at codon 877 revealed a remarkable fall in prostate-specific antigen after withdrawal of antiandrogen. Data on the other case were not available. These results indicate that a codon 877 mutation in the AR gene in advanced prostate cancer evokes the antiandrogen withdrawal syndrome. To our knowledge, this report is the first description of relationship between an AR mutation at codon 877 and the antiandrogen withdrawal syndrome.

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PubMed1996

Pain caused by bone metastasis in endocrine-therapy-refractory prostate cancer.

It is of clinical importance to control pain in the management of patients with endocrine-therapy-refractory prostate cancer. To evaluate factors influencing the manifestation of pain and the relationship between characteristics of pain and prognosis, patients with pain from bone metastasis were analyzed. A total of 48 patients with endocrine-therapy-refractory prostate cancer, who showed progression of bone metastasis and were followed-up until death, comprised the present study. The patients were divided into three groups according to the grade of pain: no need for analgesics, a need for non-opioid analgesics, and a need for opioid analgesics. The time interval between the diagnosis of the endocrine-therapy-refractory state and the requirement for analgesics was estimated. Survivals from the endocrine-therapy-refractory state were calculated according to the grade of pain or the time interval to requirement for analgesics. In addition, the extent of disease, the doubling time of tumor markers at the refractory state, any change of alkaline phosphatase, and other prognostic factors were examined in relation to pain. All 22 endocrine-therapy-resistant cases at initial treatment and 18 of 26 (69%) relapsed cases required analgesics during the clinical course until death. No difference in survival was observed between the grades of pain. The patients who needed analgesics within 1 year after becoming refractory to endocrine therapy showed significantly shorter survival than those without or with analgesics more than 1 year later. Although the time elapsing before analgesics were needed was not related to the extent of disease, the patients who showed a shorter doubling time for tumor markers and/or an exponential increase in alkaline phosphatase tended to require analgesics within 1 year. In endocrine-therapy-refractory prostate cancer, the early requirement for analgesics suggests poor prognosis, and the onset of pain may be attributable not to the extent of the disease but rather to the rapid expansion of bone metastasis.

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