Comparison of T1c versus T2 prostate cancers in Japanese patients undergoing radical prostatectomy.

In order to examine the characteristics of patients with nonpalpable prostate cancer (T1c cancer) in Japan, patients treated with radical prostatectomy were compared with those with palpable (T2) cancer. Prostate-specific antigen (PSA) level in patients with T2b disease was significantly higher than those with T1c and T2a tumors. At the time of radical prostatectomy, 78%, 71% and 31% of patients with T1c, T2a, and T2b, respectively, had organ-confined disease. When insignificant cancer was defined as volume 0.5 ml or less and Gleason score less than 5, only 2 of 34 (5.9%) with clinical T1c disease were clinically insignificant. T1c cancers were clinically significant and clinicopathological features of Tlc tumors were similar to T2a tumors. PSA measurement could detect potentially curable prostate cancer.

Association of dietary fatty acids with urinary oxalate excretion in calcium oxalate stone-formers in their fourth decade.

OBJECTIVE: To examine the influence of the dietary intake of fatty acid on urinary oxalate excretion in calcium oxalate stone-formers in their fourth decade, as previous reports show that animal fat intake is associated with urinary oxalate excretion. PATIENTS AND METHODS: The dietary intake of 58 idiopathic stone-formers in their fourth decade was recorded using the dietary-record method. The patients collected 24-h urine samples at home and their urinary oxalate excretion was measured in a clinical biochemistry laboratory. The results were used to determine the relationship between the dietary intake of fatty acids and urinary oxalate excretion. Associations between urinary oxalate excretion and dietary contents of animal fat, animal protein and various fatty acids were assessed using Spearman's correlation coefficient and multiple regression. RESULTS: The dietary content of arachidonic acid was positively correlated with urinary oxalate excretion, as assessed by univariate and multivariate analysis. CONCLUSION: The association between arachidonic acid and oxalate excretion suggests that arachidonic acid increases the intestinal absorption of oxalate and increases the clearance of oxalate in the kidneys.

Discordant iodine-123 metaiodobenzylguanidine uptake area reflects recovery time dispersion in acute myocardial infarction.

lodine-123 metaiodobenzylguanidine (MIBG) uptake was reported to be reduced compared to Tl-201 (Tl) in acute myocardial infarction (AMI). Within such an area, degrees of both sympathetic neural function and ischemic myocardial cell damage are considered to be greatly dispersed. These kinds of damage were reported to effect reporalization time in myocardial cells, and we evaluated our hypothesis that extension of the discordant MIBG uptake area correlates with recovery time (RT) dispersion and relate ventricular arrhythmias in AMI. MIBG and Tl images were obtained in AMI patients. Regional Tl or MIBG uptake was estimated in 9 segments of SPECT by using four-point scoring. The total score was the sum of scores in 9 SPECT segments. ATI-MIBG was calculated by subtracting the total MIBG score from the total Tl score. Corrected RT (RTc) was measured as a signal-averaged ECG. RTc dispersion was defined as the difference between maximal and minimal RTc. The patients were assigned to two groups (group A; < or = Lown 4a, group B; > or = Lown 4b) according to the results of 24-hour Holter monitoring. A positive correlation between RTc dispersion and ATI-MIBG was found. ATI-MIBG and RTc dispersion in group B were greater than those in group A. These results suggested that ATI-MIBG could be used to predict the development of malignant ventricular arrhythmias.

Postnatal development of the testis in Japanese children based on observations of undescended testes.

BACKGROUND: Little is known about the morphological aspects of the postnatal development of the testis in Japanese children. By investigating the normal development of the testis, clinicians in urology can give better strategies to their patients. In addition, the pattern of development will improve the understanding of the effect of xenoestrogens. METHODS: Biopsied testis samples of 68 patients with undescended testes aged between 2 and 21 years were examined by light microscopy. Nineteen patients with normal histology of the bilateral testes were selected for this study. For light microscopy, paraffin sections were stained with hematoxylin and eosin. In addition, using electron microscope, Epon sections stained with lead citrate and uranyl acetate were observed. Semi-thin sections stained with toluidine blue were also used for light microscopy. RESULTS: Gonocytes were observed in the testis of the 2-year-old boys. Spermatocytes developed by 4 years of age and spermatids developed by 11 years of age. The immature Sertoli-Sertoli ectoplasmic junction was observed as early as 4 years of age, and it was completed by 9 years of age. Mature myoid cells were observed by the age of 13 years. Immature Leydig cells were found at 7 years of age and the cells matured by 13 years of age. CONCLUSION: A pattern of postnatal development of the testis in Japanese children was presented.

Prostate-specific antigen density adjusted for the transition zone for staging clinically localized prostate cancer in Japanese patients with intermediate serum prostate-specific antigen levels.

The prostate-specific antigen (PSA) density of the transition zone (PSATZ) in 45 prostate cancer patients who received radical prostatectomy with a PSA value of 4.1-10 ng/ml was determined to see whether PSATZ was useful in the prediction of extracapsular invasion of prostate cancer. The value of PSATZ for the detection of extracapsular invasion was compared with that of PSA and PSA density (PSAD). Thirty-one patients (68.9%) had pathologically organ confined cancer while 14 (31.1%) had extracapsular disease. Patients with organ confined tumor had significantly lower PSAD and PSATZ than those with non-organ confined tumor. PSATZ was superior to PSA when analyzed by receiver operating characteristics curves. In those patients with a cut-off value of 1.0 ng/ml per ml of transition zone volume, the PSATZ had a sensitivity of 43% and a specificity of 90% for prediction of extracapsular extension. The present study demonstrated that PSATZ was superior to PSA as a predictor of extracapsular invasion in intermediate PSA levels. Measurement of PSATZ may be of additional value to indicate the need for radical prostatectomy.

Detection of a coronary arterial thrombus by indium-111-oxine-labeled platelet scintigraphy.

Coronary arteriography revealed significant left anterior descending coronary artery stenosis in a 72-year-old man with a history of myocardial infarction. Stenting of the stenotic vessel was performed. Twelve hours after stenting the patient complained of chest pain but emergent coronary arteriography did not show sign of any coronary arterial stenosis. Under suspicion of coronary thrombus formation, indium-111-oxine-labeled platelet scintigraphy was performed 5 days after stenting, and revealed accumulation of indium-111-oxine in the area corresponding to the stent implantation site.

Detection of inflammation in aortic aneurysms with indium 111-oxine--labeled leukocyte imaging.

BACKGROUND: The exact cause of aortic aneurysms is not completely understood. Histologically, the atherosclerotic lesions present in an aneurysm contain numerous inflammatory cells. This finding represents active atherosclerosis, which can cause lesion expansion. In this study we investigated the role of scintigraphy in the evaluation of inflammation in aortic aneurysms. METHODS AND RESULTS: We performed imaging using indium 111-oxine--labeled leukocytes in 14 patients with aortic aneurysms (10 thoracic and 4 abdominal) diagnosed by computed tomography. Peripheral blood evidence of inflammation was assessed on the same day. In 8 patients who subsequently underwent graft replacement of the aneurysm, the excised specimen was examined for evidence of inflammatory infiltration and correlated with the scintigraphic findings. Scintigraphic accumulation of labeled leukocytes was present in 10 of the 14 patients. Although all patients had a small increase in the erythrocyte sedimentation rate, there was no significant difference in the erythrocyte sedimentation rate between patients with positive and negative scintigram results. In 5 of the 8 surgical patients with positive scintigram results, the resected specimens demonstrated numerous inflammatory cells in the adventitia of the aortic wall and atherosclerotic changes in the media. There was no correlation between the presence of periaortic inflammatory adhesions at the time of surgery and the scintigraphic results. CONCLUSIONS: The accumulation of In-111-oxine--labeled leukocytes is a potentially useful scintigraphic marker of inflammatory infiltration in aortic aneurysms.

Activation of Na+/H+ exchanger is associated with hyperinsulinemia in borderline hypertensive rats.

Activation of Na+/H+ exchanger (NHE) is known to be related to elevated blood pressure in hyperinsulinemia. To test whether there is the change in NHE activity in insulin resistance, we measured NHE activity of platelets in fructose-induced hyperinsulinemia in Wistar-Kyoto rats (WKY), in borderline hypertensive rats (BHR), and in spontaneously hypertensive rats (SHR). All rats were fed a 60% fructose diet for 4 weeks to induce hyperinsulinemia and hypertriglyceridemia. Intracellular pH (pHi) was measured with a pH-sensitive fluorescent dye 2'7'-bis (2-carboxyethyl)-5-carboxyfluorescein acetoxymethyl ester. NHE activity was evaluated by the recovery of pHi following addition of sodium propionate (Vmax). Measurement of intracellular calcium ([Ca2+]i) was performed using fura2/acetoxymethylester. Systolic blood pressure in fructose diet BHR elevated significantly greater than that in control diet BHR with the increase of both [Ca2+]i and Vmax. In WKY, there was no significant increase in systolic blood pressure and [Ca2+]i except Vmax in a fructose diet. Vmax in control diet SHR was greater than in control diet WKY and BHR, and we found no additional increase in Vmax with a fructose diet in SHR. In BHR, a high salt diet increased systolic blood pressure and Vmax to a similar degree as a fructose diet or a high salt combined with a fructose diet. Plasma insulin concentration correlated positively with Vmax in WKY and BHR, but not SHR. A fructose diet induces hyperinsulinemia and elevates blood pressure in BHR. Hyperinsulinemia appears to activate NHE in a different manner in SHR, and might be associated with an elevation in blood pressure in BHR.

Usefulness of indium-111-oxine-labeled leukocyte scintigraphy in diagnosis of inflammation associated with chronic aortic dissection.

BACKGROUND: Patients with chronic aortic dissection require monitoring for indications of disease progression. In present study, inflammation adjacent to associated aortic wall was evaluated by indium-111-oxine-labeled leukocyte scintigraphy, scince inflammation of the blood vessel wall often associates with progression of chronic aortic dissection. METHODS AND RESULTS: Fifteen patients with aortic dissection underwent indium-111-oxine-labeled leukocyte scintigraphy. Seven showed positive images at sites corresponding to the actual sites of the dissociated aorta. Four patients with positive images underwent surgery. Histologic examination revealed inflammatory and necrotic changes of the aortic wall. During a mean follow-up period of 2.3 years, progression of aortic dissection was observed in two of the seven patients with positive intimal imaging. CONCLUSION: Indium-111-oxine-labeled leukocyte scintigraphy may be a useful noninvasive technique to assess the persistent inflammation in patients with chronic aortic dissection.

Serum soluble Fas level for detection and staging of prostate cancer.

To evaluate the clinical usefulness of measuring serum soluble Fas (sFas) for differentiation between prostate cancer and benign prostate hyperplasia (BPH) and for staging of prostate cancer, serum sFas and PSA were determined in 38 and 20 men with prostate cancer and BPH, respectively, before treatment. In 17 patients, sFas and PSA were measured one hour after transrectal ultrasound-guided sextant biopsy in order to examine the leakage of sFas into the circulation after prostatic injury. Patients with prostate cancer had a significantly higher level of sFas than those with BPH. The serum sFas level was statistically elevated in patients with metastatic prostate cancer. There was a statistically significant correlation between sFas and PSA in patients with prostate cancer but not in those without cancer. The serum sFas did not change one hour after systematic prostatic biopsy although PSA levels were markedly elevated. sFas levels might be useful as a discriminator between prostate cancer and BPH while sFas might indicate the tumor burden in patients with prostate cancer.

Prostate-specific antigen, prostate volume and transition zone volume in Japanese patients with histologically proven benign prostatic hyperplasia.

The relationship among age, prostate-specific antigen (PSA) level and prostate volume in Japanese patients with lower urinary tract symptoms (LUTS) and histologically proven benign prostatic hyperplasia (BPH) was examined in order to assess the utility of PSA as a predictor of prostate volume. Two hundred eighteen patients with LUTS were confirmed to have BPH by histological examination for the reason of elevated PSA and/or abnormal digital rectal examination finding. Correlation among PSA, prostate volume and transition zone volume were analyzed in patients classified into age-stratified groups. Prostate volume increased with age. Mean serum PSA increased with age, and the correlation of PSA and prostate volume was determined to be statistically significant in each cohort of age. A correlation coefficient ranged from 0.315 to 0.439. In patients with LUTS and clinical BPH, serum PSA increased with age and was related to prostate volume. PSA might be useful for therapeutic decision making for patients with symptomatic BPH.

Changes in cell proliferation and apoptosis during local progression of prostate cancer.

To determine the changes in biological features of the prostate during the course of local recurrence of prostate cancer after endocrine therapy, histologic grade, proliferating activity and apoptotic indices were examined in prostate specimens obtained before treatment and at recurrence. A total of 16 patients, who had received endocrine therapy and eventually recurred in the prostate, were evaluated. Histologic grade was determined by the method of Gleason and the number of proliferating cells and apoptotic cells were counted. Tumors with a high grade Gleason score remained at a high grade. A statistically significant increase in the number of Ki-67 positive cells was observed from pretreatment biopsy to local recurrence. On the other hand, the apoptotic index decreased during progression. Patients with a higher number of Ki-67 positive cells before the initial treatment had a poorer prognosis than those with a lower number of Ki-67 positive cells. In conclusion, prostate cancer shows an increase of malignant potential as assessed by the number of Ki-67 positive cells, whilst the decrease in apoptosis might play some role in the course of progression.

[Preventive effect of chlormadinone acetate on flare-up phenomenon in advanced prostate cancer administered with a luteinizing hormone-releasing hormone analogue].

To investigate whether chlormadinone acetate (CMA) could prevent the flare-up phenomenon induced by a luteinizing hormone-releasing hormone analogue (LH-RHa), we treated 4 cases of stage C and 17 cases of stage D prostate cancer with CMA for 4 weeks and CMA plus monthly injection of LH-RHa for following 24 weeks. Serum LH, testosterone, and prostate-specific antigen (PSA) levels were closely monitored before and 3 days, 1-, 2-, and 4-weeks after LH-RHa injection. Subjective and objective responses were also investigated. Serum LH and testosterone levels significantly elevated 3 days after the initial injection of LH-RHa. However, they resumed 1 week after LH-RHa injection with fluctuation under the normal range. Out of 21 cases, 3 cases (14%) consisting of 2 poorly and 1 moderately differentiated adenocarcinoma showed increased serum PSA levels 1 week after LH-RHa injection in spite of suppressed serum testosterone levels. The objective response of these 2 poorly differentiated cases was progressive disease at 24 weeks. No cases indicated worsening of clinical symptoms concerning flare-up phenomenon. CMA seemed to be capable of preventing flare-up phenomenon in advanced prostate cancer.

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.

Effect of dietary intake on urinary oxalate excretion in calcium oxalate stone formers in their forties.

PURPOSE: To examine the influence of dietary intake on urinary oxalate excretion in calcium oxalate stone formers in their forties. PATIENTS AND METHODS: Dietary intake was recorded by using the dietary-record method in 58 idiopathic stone formers in their forties. The patients collected their urine for 24 h at home and their urinary oxalate excretion was measured. The relationship between the dietary intake of various nutrients and urinary oxalate excretion was examined by mono- and multivariate analysis. RESULTS: The intake of animal fat was correlated with urinary oxalate excretion by monovariate analysis, but that of total protein, animal protein, calcium and carbohydrate were not. By multivariate analysis, the intake of animal fat was correlated with urinary oxalate excretion and the intake of calcium was inversely correlated with urinary oxalate excretion. CONCLUSION: The intake of animal fat was positively and the intake of calcium was negatively correlated with the urinary oxalate excretion in stone formers in their forties. It was shown that animal fat plays an important role in urinary oxalate excretion.

Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: a comparison of 123I-MIBG scintigraphic and echocardiographic data.

It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123I-MIBG scintigraphy. Both of these methods are associated with beta-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patients with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography: and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123 [123I] meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r = 0.682, p = 0.0146), wall motion after dobutamine stress (r = 0.758, p = 0.0043), the change in wall motion (r = 0.667, p = 0.0178), and with left ventricular diastolic diameter (r = 0.837, p = 0.0007). In addition, the 123I-MIBG washout rate correlated with baseline wall motion (r = 0.608, p = 0.0360), wall motion after dobutamine stress (r = 0.703, p = 0.0107), and with the change in wall motion (r = 0.664, p = 0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure.

Vitamin D receptor gene polymorphism in Japanese patients with prostate cancer.

Vitamin D receptor gene polymorphism was determined in 66 and 60 Japanese patients with prostate cancer and non cancer controls, respectively. In contrast to previous reports showing an association between vitamin D receptor polymorphism of a TaqI restriction fragment length polymorphism at codon 352 (genotype tt) and prostate cancer in an American population, the frequency of genotype tt is less than one percent in the Japanese population. There was no difference between the patients and the controls in the vitamin D receptor TaqI genotype. In patients with metastatic prostate cancer, genotype TT had a tendency to shorter progression free survival compared to genotype Tt, but the number of patients was limited.

Identification of a I-cM region of common deletion on 13q14 associated with human prostate cancer.

Frequent allelic losses on chromosome arm 13q are observed in carcinomas of the head and neck, breast, ovary, and pituitary gland. We analyzed 59 primary prostate tumors (stage B, 18 patients; C, 12 patients; D1, 4 patients; and endocrine therapy-resistant cancer death, 25 patients), as well as 18 metastatic tissues from 14 of the 25 cancer death patients for loss of heterozygosity (LOH) using 35 microsatellite markers on chromosome arm 13q. Of the 59 primary tumors, 31 (53%) showed LOH involving at least one locus. Detailed deletion mapping identified a distinct commonly deleted region in the I-cM interval flanked by D13S153 and D13S273 on 13q14 and this region overlapped a part of the RB1 gene. Paired DNAs were available from both primary and metastatic tumors in the 14 cases of cancer death; among those pairs, we detected LOH on 13q in seven (50%) primary tumors, and in all metastatic foci (P = 0.0029). Moreover, the regions lost in metastatic tissues were more extensive than those seen in the corresponding primary tumors. These results suggest that inactivation of a putative tumor suppressor gene(s) including the RB1 gene on 13q14 plays an important role in human prostate cancer.