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Jun Nakashima

Publications and source records attributed to Jun Nakashima.

31 records · Page 2Linked to original sources
PubMed2003

Prediction of extraprostatic cancer by prostate specific antigen density, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer.

BACKGROUND: The present study was designed to identify the preoperative parameters, including PSA-based parameters, and endorectal MRI, predictive of pathological stage in males who underwent radical prostatectomy. METHODS: We studied 114 patients who underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized prostate cancer. Clinical stage was assessed by DRE, pelvic CT scan, endorectal MRI, and bone scan. The correlation between the preoperative parameters, including PSA-based parameters, clinical stage, and histological findings of biopsy specimens, and the pathological stage was analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for local extent of disease. RESULTS: Seventy-six (66.6%) patients had organ confined cancer and 38 (33.4%) patients had extraprostatic cancer. Of the 38 patients with extraprostatic cancer, four had seminal vesicle involvement, while, none had pelvic lymph node involvement. Biopsy Gleason score, PSA, PSA-alpha1-antichymotrypsin (PSA-ACT), PSA-density (PSAD), PSA-transition zone density, PSA-ACT density, and PSA-ACT transition zone (TZ) density were significantly higher and percent free PSA was lower in the patients with organ confined cancer than those with extraprostatic cancer (P < 0.01). PSAD showed the largest area under the ROC curve (AUC) among those parameters (AUC = 0.732). Sixty-eight (74.7%) of 91 patients with T2 on endorectal MRI had organ confined cancer, while 15 (65.2%) of 23 patients with T3 had extraprostatic cancer (P < 0.01). Multivariate logistic regression analysis indicated that Gleason score (> or =7 vs. < or =6), endorectal MRI findings, and PSAD were significant predictors of extraprostatic cancer (P < 0.01). CONCLUSIONS: The present study demonstrated that preoperative PSAD was the most valuable predictor among PSA-based parameters for extraprostatic disease in patients with clinically localized prostate cancer. The combination of PSAD, endorectal MRI findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.

Aged↗
PubMed2003

Suppression of hormone-refractory prostate cancer by a novel nuclear factor kappaB inhibitor in nude mice.

We have synthesized and explored the feasibility of using a novel nuclear factor (NF) kappaB inhibitor, a dehydroxymethylepoxyquinomicin designated as DHMEQ, against prostate cancer. The activity of NFkappaB, evaluated by transient transfection of a luciferase reporter DNA containing a specific binding sequence for NFkappaB, was inhibited by DHMEQ in three human hormone-refractory prostate cancer cell lines, DU145, JCA-1, and PC-3. Statistically significant growth inhibition was achieved by 20 micro g/ml of DHMEQ, and marked levels of apoptosis were induced 48 h after DHMEQ administration in vitro. Electrophoretic mobility shift assay showed that DHMEQ completely inhibited NFkappaB DNA binding activity in JCA-1 cells. Furthermore, i.p. administrations of DHMEQ significantly inhibited pre-established JCA-1 s.c. tumor growth in nude mice without any side effects. Our result indicates the possibility of using a novel NFkappaB activation inhibitor, DHMEQ, as a new treatment strategy against hormone-refractory prostate cancer.

Animals↗
PubMed2003

Incidence and growth pattern of simple cysts of the kidney in patients with asymptomatic microscopic hematuria.

BACKGROUND: We examined the incidence and natural history of simple renal cysts found by ultrasonography (US) in patients referred for asymptomatic microscopic hematuria. METHODS: Among the 906 patients aged 18-78 years, 743 patients who had undergone US were included in the present study. The natural history of simple renal cysts was investigated in 55 patients who underwent periodical US examinations for more than 3 years. RESULTS: The incidence of simple renal cysts was 4.3% for ages 29 years or younger, 15.3% for ages 30-39, 21.8% for ages 40-49, 23.3% for ages 50-59 and 32.6% for ages 60 years or older; thus the incidence increased in older age groups (P = 0.0005 for men, P = 0.0020 for women). Men tended to have a higher incidence than women. The degree of hematuria did not influence the incidence of renal cysts (P = 0.9044). The annual growth rate of the mean maximum diameter was 4.2% during a 3-year follow-up period in 55 patients and 5.1% during a 6-year follow-up in 31 patients. CONCLUSION: Since the diameter of a renal cyst may increase by 5% annually, the diameter of the cyst may increase by 1.6 times in 10 years. The scheduling of follow-up examinations depends on the size at the time of disclosure, the effects on calyceal systems, or the suspicion of a concurrent malignant disease. However, the most simple renal cysts may be followed-up at an interval of more than 10 years, once a diagnosis has been established.

Adolescent↗
PubMed2003

Enhancement of diethylstilbestrol induced cytotoxicity by bcl-2 antisense oligodeoxynucleotides and a glutathione depletor for prostate cancer.

PURPOSE: Bcl-2 has been shown to prolong cancer cell survival by blocking apoptosis and have the function of scavenging reactive oxygen species. We assessed the efficacy of a novel strategy that relies on antisense bcl-2 oligodeoxynucleotides as well as a glutathione depletor combined with diethylstilbestrol (DES) for hormone independent prostate cancer. MATERIALS AND METHODS: The cytotoxic effects of antisense bcl-2 oligodeoxynucleotides and DES on PC-3 cells were determined using spectrophotometry measurement. The expression of Bcl-2 protein was detected by Western blot analysis. Intracellular reactive oxygen species generation was estimated from the amount of intracellular dichlorofluorescein. Apoptosis was determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling assay. RESULTS: Antisense bcl-2 oligodeoxynucleotides decreased Bcl-2 protein levels and significantly inhibited PC-3 cell growth in a dose dependent manner. Antisense bcl-2 oligodeoxynucleotides significantly enhanced DES induced cytotoxicity. A significant increase in apoptotic cells was induced by the combination of antisense bcl-2 oligodeoxynucleotides and DES compared with the oligodeoxynucleotides alone. The glutathione depletor buthionine sulfoximine significantly decreased the intracellular concentration of glutathione and augmented DES induced cytotoxicity and reactive oxygen species generation in PC-3 cells. Neither the generation of reactive oxygen species nor the intracellular concentration of glutathione was influenced by antisense bcl-2 oligodeoxynucleotide treatment. CONCLUSIONS: Antisense bcl-2 oligodeoxynucleotides significantly enhanced DES induced cytotoxicity in hormone independent prostate cancer cells through the apoptotic pathway independent of augmented reactive oxygen species generation, whereas the glutathione depletor augmented cytotoxicity and reactive oxygen species generation.

Apoptosis↗
PubMed2003

Prognostic implication of microvascular invasion in biochemical failure in patients treated with radical prostatectomy.

INTRODUCTION: Micrometastasis before radical prostatectomy (RP) is considered to be related to the biochemical failure after surgery in patients with prostate cancer. To predict the biochemical failure, we evaluated microvascular (lymphatic/vascular) invasion and other pathological findings as prognostic factors for biochemical failure after RP. MATERIALS AND METHODS: Eighty-two men who underwent RPs and received neither preoperative nor postoperative adjuvant therapy were analyzed. Pathological findings of each patient were carefully reviewed to determine pathological factors predicting biochemical failure. The influence of pathological findings on the biochemical failure was evaluated. RESULTS: The overall biochemically assessed disease-free survival rate was 55.7% at 3 years. By univariate analysis, Gleason sum, capsular penetration, and microvascular invasion were significantly associated with the rate of biochemical failure. Microvascular invasion was strongly correlated with Gleason sum, capsular penetration, surgical margin, perineural invasion, and pathological stage. By multivariate analysis, Gleason sum, capsular penetration, and microvascular invasion were independent predictors of biochemical failure. CONCLUSION: This study suggests that in addition to Gleason grade and capsular penetration, microvascular invasion is one of independent prognostic factors in patients with prostate cancer treated with RPs.

Aged↗
PubMed2003

Antitumor effect of a novel nuclear factor-kappa B activation inhibitor in bladder cancer cells.

Nuclear factor (NF)-kappaB is a transcription factor that not only induces and controls various genes, including those of inflammatory cytokines, but also activates genes which suppress apoptosis. It has been clearly demonstrated that certain advanced human bladder cancer cells constitutively acquire the ability to activate NF-kappaB, which not only protects cancer cells from apoptotic cell death, but also upregulates the production of various cytokines that may increase the malignant potential of the disease and cause paraneoplastic syndromes. The NF-kappaB inhibitors may therefore be useful as anticancer agents. An NF-kappaB function inhibitor, a dehydroxymethyl derivative of epoxyquinomicin C (DHMEQ), has recently been designed and synthesized. The effectiveness of DHMEQ against advanced human bladder cancer cell line KU-19-19, in which NF-kappaB is constitutively activated, has been investigated. The DNA-binding activity of NF-kappaB was completely inhibited following 2-6-h exposure to 10 microg/ml of DHMEQ. Marked levels of apoptosis were observed 48 h after DHMEQ administration. These results confirmed that NF-kappaB activation maintains the viability of KU-19-19 cells, that DHMEQ inhibited constitutively activated NF-kappaB, and, consequently, apoptosis was induced. However, it was still possible that DHMEQ caused apoptotic cell death through some other mechanism which has not yet been fully investigated. The authors conclude that DHMEQ could represent a new treatment strategy against advanced bladder cancer.

Animals↗
PubMed2002

Can initial prostate specific antigen determinations eliminate the need for bone scans in patients with newly diagnosed prostate carcinoma? A multicenter retrospective study in Japan.

BACKGROUND: The objective of the current study was to assess rigorously whether serum prostate specific antigen (PSA) determination can eliminate the need for bone scans in Japanese patients with newly diagnosed prostate carcinoma with serum PSA levels < or = 10 ng/mL. METHODS: A retrospective assessment of 1294 patients with newly diagnosed, untreated prostate carcinoma was conducted at the authors' institutions. All patients underwent a bone scan, serum PSA measurement, and core needle biopsy of the prostate. The receiver operating characteristic curve for identifying a positive bone scan based on serum PSA levels and a decision tree were analyzed to determine the expected 10-year cumulative cost and disease specific survival rate. Two competing strategies were used: PSA alone and PSA plus baseline bone scan. For the PSA-alone strategy, a baseline bone scan was performed only when the patient had a serum PSA level > 10 ng/mL. RESULTS: The proportion of positive bone scans in patients with serum PSA levels < or = 10.0 ng/mL was 1.33%. The area under the receiver operating characteristic curve was 0.870. Patients with a Gleason Grade > or = 3 tumors or with a Gleason score > or = 7 had a higher proportion of positive bone scans. The 10-year disease specific survival rates with the PSA-alone strategy and the PSA-plus-bone-scan strategy were the same. The PSA-alone strategy was minimally cost effective, with a savings of $16.00 (U.S.) in the cumulative net cost per patient over the PSA-plus-bone-scan strategy. CONCLUSIONS: The current results suggest that baseline bone scans can be eliminated in patients with newly diagnosed prostate carcinoma in Japan who have serum PSA levels < or = 10 ng/mL. Apparently, it is possible to omit baseline bone scans for patients with a Gleason Grade < or = 2 tumors or with a Gleason score < or =6.

Adult↗
PubMed2002

Clinical value of prostate specific antigen based parameters for the detection of prostate cancer on repeat biopsy: the usefulness of complexed prostate specific antigen adjusted for transition zone volume.

PURPOSE: To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy. RESULTS: Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer. CONCLUSIONS: alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.

Aged↗
PubMed2002

Long-term effects of transurethral microwave thermotherapy.

BACKGROUND: To identify the clinical valuables predicting a favorable outcome after transurethral microwave thermotherapy (TUMT) of the prostate with Prostatron. METHODS: One hundred and two patients with lower urinary symptoms were treated with TUMT using a Prostatron device with the low-energy protocol (Prostasoft version 2.0 J). The pre-operative subjective score and objective voiding parameters were collected from the medical record. To test the differences in the risk of the necessity for additional treatments for several subgroups, Kaplan-Meier survival analyses and log-rank tests were used. RESULTS: The Kaplan-Meier analyses showed that 67% of the patients received additional treatment within five years. The median period for receiving additional treatment was 37 months. The patients with a peak flow rate greater than 6.5 mL per second, with a urethral length less than 40 mm, or with an age over 64 years all demonstrated a significantly longer period before receiving additional treatment, when compared with their counterparts. These three factors were also significant in multivariate analysis to predict the long-term outcome. CONCLUSIONS: Overall durability of TUMT was limited. Aged patients with a relatively high peak flow rate or with a short prostatic urethral length resulted in lower risk of receiving additional treatments after TUMT.

Aged↗
PubMed2002

Significance and diagnostic accuracy of renal calculi found by ultrasonography in patients with asymptomatic microscopic hematuria.

BACKGROUND: The purpose of the present study was to evaluate the clinical significance and the accuracy of the diagnosis of renal calculi incidentally found by ultrasonography (US). METHODS: A total of 906 subjects (639 men and 267 women) aged 18-78 years were referred for asymptomatic microscopic hematuria. Of these, 743 patients who underwent US were studied. RESULTS: Hyperechogenic spots in the central echo complex suggesting renal calculi were noted in 195 patients (21.5%). The occurrence of hyperechogenic spots was higher in patients with 20 or more urinary red blood cells per high-power field (chi(2) = 4.896, P = 0.0269) and in men than in women (chi(2) = 7.101, P = 0.0077), but it was lowest in patients who were 29 years old or younger. Of these 195 patients, who were followed up for 1-161 months (average: 33.5 months), 24 patients (12.3%) needed urological management. Extracorporeal shockwave lithotripsy was carried out in eight patients, transureteral lithotripsy was carried out in three patients, spontaneous passage occurred in 11 patients and medication for hyperuricemia was initiated in two patients (1%). Among the patients in whom hyperechogenic spots were found on the kidney by US but calculi were not visible on abdominal plain radiographs, 39 patients underwent computed tomography. Of them, 31 patients were confirmed to have renal calculi. CONCLUSION: The obtained results suggest that US is an effective and reliable means of detecting renal calculi in patients with asymptomatic microscopic hematuria, and in facilitating prompt urological intervention or predicting the natural course of renal calculi.

Adult↗
PubMed2002

Hypercalcemia and acute renal failure caused by production of parathyroid hormone-related protein from renal cell carcinoma.

A 69-year-old male patient was diagnosed with right-sided renal cell carcinoma and humoral hypercalcemia of malignancy caused by an excessive production of parathyroid hormone-related protein. The hypercalcemia led to acute tubular necrosis, so the patient had to be put on hemodialysis. The renal failure was accompanied by hyponatremic encephalopathy. Rapid correction of the hyponatremia might have initiated central pontine myelinolysis.

Acute Kidney Injury↗