Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats.

PURPOSE: The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity. METHODS: Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON. RESULTS: Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did not change micturition parameters. CONCLUSIONS: These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.

FDG PET for evaluating the change of glucose metabolism in prostate cancer after androgen ablation.

In the clinical study of prostate cancer, the effect of androgen ablation on glucose metabolism in cancer tissue has not been elucidated. The purpose of this study was to investigate the change in glucose utilization due to endocrine therapy for prostate adenocarcinoma. Ten patients with histologically proven prostate cancer were prospectively investigated with (18)F-fluorodeoxyglucose and positron emission tomography (FDG PET) prior to and after the initiation of endocrine therapy. FDG uptake was calculated to measure glucose utilization in cancer tissue. The change in FDG accumulation was compared with changes in serum prostate specific antigen (PSA) level and prostate size. FDG accumulation in the prostate decreased in all patients 1-5 months after the initiation of hormone therapy. The serum PSA level and prostate size measured on computerized tomography (CT) also decreased in these periods. A decrease in FDG accumulation was also demonstrated in metastatic sites. In this study, there appeared to be a decrease in FDG uptake in prostate cancer after endocrine therapy not only in primary prostate cancer lesions but also at metastatic sites, suggesting that the glucose utilization by tumours was suppressed by androgen ablation.

Prognostic value of nuclear area index in combination with the World Health Organization grading system for patients with renal cell carcinoma.

OBJECTIVES: To assess the diagnostic accuracy of the World Health Organization (WHO) grading system for renal cell carcinoma (RCC) in terms of nuclear size evaluation. Furthermore, the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal tubular cells, is investigated. METHODS: Measurement of the nuclear areas of cancer and normal tubular cells was performed on the histologic slides from the 76 patients with RCC, and the distribution of MNA and NAI was compared among the WHO grades. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the progression-free and cause-specific survival of the patients was examined. RESULTS: MNA for cancer cells and NAI significantly increased according to the grade. NAI was 1.0 or less in 9 of the 10 patients with G1 tumors and more than 1.0 in 12 of the 13 patients with G3 tumors, whereas the NAI ranged widely from 0.53 to 2.0 in 53 patients with G2 tumors. By multivariate analysis, including grade and TNM categories, NAI and MNA were independent variables for survival in all the patients as well as for cancer progression in localized disease. CONCLUSIONS: WHO G2 RCCs are actually composed of tumors with varying nuclear size, and the prognosis of the patients with G2 tumors varied as well. NAI could provide improved prognostic information for the patients with RCC, especially in G2 cases.

Analysis of the mechanism of discrepant nuclear morphometric results comparing preoperative biopsy and prostatectomy specimens.

OBJECTIVES: To explore the mechanism for the differing nuclear morphometric results between needle biopsy and surgical specimens of the prostate. METHODS: In experiment 1, a comparison of mean nuclear area (MNA), volume-weighted mean nuclear volume (MNV), and form factor (FF) for prostatic epithelial cells was performed between preoperative needle biopsy and prostatectomy specimens from 5 patients with benign prostatic hyperplasia (BPH). In experiment 2, a scheduled, sequential ex vivo needle sampling from the enucleated prostates (at 0, 2, 6, and 24 hours after surgical resection) was also performed for 7 patients with BPH. The prostatectomy specimens were left unfixed for 2 hours until the second needle sampling was done. Nuclear morphometric parameters were measured on the needle-sampled as well as on the prostatectomy specimens. RESULTS: MNA, MNV, and FF of BPH cells measured on preoperative biopsy specimens were smaller than those of surgical specimens in all 5 of the cases. The results of nuclear morphometry on the materials obtained by ex vivo needle sampling of prostates before and during fixation revealed that the MNA, MNV, and FF for BPH cells of 0-hour specimens were significantly smaller than those for needle samples at 2, 6, and 24 hours after surgical resection as well as those for prostatectomy specimens. CONCLUSIONS: The present study provided further evidence that the ischemic damage caused by delayed fixation could result in a substantial change of the nuclear morphology of prostate cells. An immediate start, as well as a rapid completion, of the fixation procedure seems critical for an accurate nuclear morphometry of prostatectomy specimens.

Prognostic value of nuclear morphometry on needle biopsy from patients with prostate cancer: is volume-weighted mean nuclear volume superior to other morphometric parameters?

OBJECTIVES: To compare the prognostic value of stereologically estimated volume-weighted mean nuclear volume (MNV) with other nuclear morphometric parameters using pretreatment needle-biopsy specimens of prostate cancer. METHODS: The MNV, mean nuclear area, form factor, and coefficients of variation for nuclear area (VNA) and form factor were measured on pretreatment needle biopsy specimens from 66 patients with prostate cancer (clinical Stage B, n = 9; Stage C, n = 14; and Stage D, n = 43), all of whom underwent androgen deprivation therapy. The prognostic value of those morphometric parameters, as well as Gleason score and clinical stage, was examined in terms of cause-specific patient survival using univariate and multivariate analysis (Cox proportional hazard model). RESULTS: Univariate analysis of the nuclear morphometric parameters revealed that MNV, mean nuclear area, VNA, coefficient of variation for form factor, and clinical stage were significant prognostic factors for cause-specific patient survival. However, when the patients with Stage D disease were selectively analyzed for survival, only the VNA was a significant prognostic parameter. Furthermore, the multivariate analysis, including the morphometric parameters, clinical stage, and Gleason score revealed that only VNA and clinical stage were independent variables. CONCLUSIONS: The present comparative study could not demonstrate any prognostic superiority of MNV over other nuclear morphometric parameters in patients with prostate cancer.

[Evaluation of prostate cancer using FDG-PET].

The clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was examined in 54 patients with prostate cancer. FDG accumulation was positive in 38 of 54 the prostates (70%), 3 of 8 the lymph node metastases (38%) and 10 of 16 the bone metastases (63%), which suggested that FDG-PET is not superior to other conventional imaging methods as a tool for tumor detection. On the other hand, a quantitative value for FDG uptake in the prostate, expressed as a standardized uptake value (SUV), significantly correlated to the histological grade, clinical stage and serum PSA of the patients. A decrease of SUV was observed in all the patients who responded to endocrine treatment, and the patients with high pre-treatment SUV were shown to be at the risk for disease progression after initial treatment. The present results indicated that FDG-PET could provide us with useful prognostic information for the patients with prostate cancer by evaluating the malignant potential of the tumor.

Ratio of gamma-seminoprotein to prostate-specific antigen for the detection of prostate cancer: its discrimination power could be influenced by the assay methods of PSA and/or gamma-seminoprotein.

BACKGROUND: The ratio of gamma-seminoprotein (gamma-Sm) and prostate-specific antigen (PSA) has been regarded as being superior over PSA alone as a discriminator between prostate cancer and benign prostatic diseases. In previous studies, PSA and gamma-Sm were measured by the Eiken kit and the old-version or revised Chugai kit, respectively. We compared the power of gamma-Sm ratio with that of PSA alone when using Markit-M PSA assay and the revised Chugai gamma-Sm assay. METHODS: Fifty-three patients with prostate cancer having no metastasis and 116 with benign prostatic diseases were enrolled in this study. Prostate-specific antigen was measured by Markit-M kit and gamma-Sm was measured by the revised Chugai kit. The discrimination power of gamma-Sm ratio and PSA alone was evaluated with receiver operating characteristic (ROC) curves. Comparisons between prostate cancer and benign diseases were performed with Mann Whitney U-test and Fisher's exact test. RESULTS: The optimal cut-off value was set at 3.1 ng/mL for PSA and 0.935 for gamma-Sm ratio. Sensitivity, specificity and positive predictive value of PSA alone were 81.1, 81.0 and 66.2%, respectively, while those of gamma-Sm ratio were 73.6, 90.5 and 78.0%, respectively. There was no statistical significance in each value between PSA and gamma-Sm ratio. Areas under the ROC curves of PSA and gamma-Sm ratio were 0.881 and 0.866, respectively (P>0.05). CONCLUSION: Contrary to the previous reports, gamma-Sm ratio and PSA were not different in the discrimination between prostate cancer and benign prostatic diseases, which suggested that the discrimination power of gamma-Sm ratio, and presumably that of the free PSA to total PSA ratio as well, could be considerably influenced by the assay kits for serum PSA and/or gamma-Sm (free PSA) used. Therefore, the clinical significance of gamma-Sm ratio should be evaluated for each PSA assay kit.

Comparison of nuclear morphometric results between needle biopsy and surgical specimens from patients with prostate cancer.

OBJECTIVES: To compare nuclear morphometric values and Gleason scores between biopsy and radical prostatectomy specimens in patients with clinically localized prostate cancer. METHODS: The mean nuclear area (MNA), volume-weighted mean nuclear volume (MNV), and form factor (FF) were measured on the 18-gauge needle biopsy and radical prostatectomy specimens of 25 patients with clinically localized prostate cancer. The correlation between biopsy and surgical specimens was investigated for MNA, MNV, FF, and Gleason scores. RESULTS: The average values for the MNA, MNV, and FF of the biopsy specimens (36.2 microm2, 366 microm3, and 0.86, respectively) were significantly smaller than those of the prostatectomy specimens (51.4 microm2, 646 microm3, and 0.91) by Student's paired t test. The Pearson correlation of morphometric parameters between the biopsy and surgical specimens was significant only for FF. A comparison of histologic grading between the biopsy and surgical specimens revealed identical Gleason scores in 32% and identical grades (on a three-grade system) in 68% of all the cases. CONCLUSIONS: Discrepant nuclear morphometric results were observed between biopsy and surgical specimens of localized prostate cancer. The reason for such differing results is unclear but may be caused by artifacts associated with tissue sampling and processing. It is recommended that data obtained by biopsy should be considered separately from that obtained from surgical specimens.

Immunohistochemical expression of p53 and bcl-2 proteins is not associated with sarcomatoid change in renal cell carcinoma.

An immunohistochemical study was conducted to examine the expression of p53 and bcl-2 proteins in RCC (renal cell carcinoma) with sarcomatoid change in order to determine whether abnormalities in those proteins are associated with an enhanced malignant potential of RCC. Paraffin-embedded tissues from 11 patients with RCC, in which sarcomatoid change was prominent, were stained using anti-p53, bcl-2 and Ki-67 antibodies. Immunoreactivities for these antibodies were compared between the sarcomatoid components and corresponding basic histologic (clear or papillary) components in individual cases. Measurement of the mean nuclear areas of each component was also performed using an image analyzer system. There was no substantial increase in immunoreactivity for p53 or bcl-2 proteins in sarcomatoid components as compared with basic components. In contrast, the percentage of Ki-67-positive cells and the mean nuclear area were significantly larger in sarcomatous components than in basic components. The expression of p53 and bcl-2 proteins was not likely to play a major role in the sarcomatoid change of RCC.

Long-term treatment results of elderly patients with prostate cancer in Japan: an analysis of prognostic factors.

BACKGROUND: The management of elderly patients with prostate cancer is an important issue because the incidence of prostate cancer is high in old men, and people are also living longer today. The present retrospective study was therefore conducted to evaluate the long-term clinical outcome of elderly patients with prostate cancer and to analyze the prognostic factors. METHODS: Between 1980 and 1992, 151 patients aged 75 to 89 years old were diagnosed as having prostate cancer. The patients were initially managed by hormonal therapy in 117, radical prostatectomy in 11, external radiotherapy in 20, chemotherapy in 1 and no treatment in 2 cases. The clinical outcome of the patients was analyzed in relation to clinical stage, histological grade and treatment methods received. RESULTS: By univariate analysis, the stage and treatment methods were significant variables for overall and cause-specific survival rates, and grade was a significant variable for cause-specific survival rate of the patients. However, multivariate analysis revealed that stage was the only independent prognostic factor for overall as well as cause-specific survival of the patients. Among the patients with stage A2-B disease, a comparison between those treated definitively and non-definitively revealed no difference in terms of overall and relative survival rates. CONCLUSIONS: The presence of advanced prostate cancer disease had the greatest impact on the survival of the elderly patients. On the other hand, localized prostate cancer was satisfactorily managed with non-definitive almost as well as with definitive treatment.

Prognostic value of sarcomatoid histology and volume-weighted mean nuclear volume in renal cell carcinoma.

OBJECTIVE: To determine the prognostic value of two histopathological factors, sarcomatoid histology and volume-weighted mean nuclear volume (MNV) in renal cell carcinoma (RCC). PATIENTS AND METHODS: The study included 106 patients (72 men and 34 women, mean age 63 years, range 32-83) with RCC, all of whom were surgically treated between 1985 and 1995. The presence of any sarcomatoid component was determined and MNV estimated using a stereological method in histological slides of tumour specimens from these patients. The prognostic significance of the two variables was evaluated by univariate and multivariate analyses in comparison with other histopathological variables (T, N and M categories, nuclear grade, tumour size, tumour type), using the cause-specific and progression-free survival of the patients as the endpoints. RESULTS: Among the 106 RCC cases examined, a sarcomatoid component was detected in 34 (32%); the MNV was 90-627 micro3 (mean 225). By univariate and multivariate analysis, both variables were significant prognostic factors for cause-specific survival in all patients. In addition, multivariate analysis of the 74 patients with localized RCCs (T1-3, N0 M0) showed that sarcomatoid histology was a significant prognostic factor for disease progression. CONCLUSION: The presence of sarcomatoid histology and the MNV, both of which can be examined with no specialized laboratory procedures, seem to be useful tumour-related prognostic factors in RCC.

[Quality of life in patients with testicular cancer after high orchiectomy, radiation therapy or chemotherapy].

We evaluated the physical or psychosocial states of testicular cancer patients receiving orchiectomy, radiation therapy and chemotherapy to assess their quality of life during and after treatment. The subjects were 33 post-treatment patients with testicular cancer who responded to the questionnaire we mailed to them. The quality of life score during chemotherapy showed a decrease, which was accompanied by gastrointestinal symptoms induced by anti-cancer drugs. With regard to the difference in adjuvant treatment types, the surveillance group showed the highest score in the satisfaction of daily life. Moreover, married patients tended to be satisfied with daily life more than non-married patients. With regard to sexual or erectile function, scores of testicular cancer patients, especially in the retroperitoneal lymph node dissection group, were inferior to these of normal volunteers. In conclusion, the physical or psychosocial states after treatment for testicular cancer depend not only on treatment type but also marriage status.

The increased accumulation of [18F]fluorodeoxyglucose in untreated prostate cancer.

BACKGROUND: To evaluate the clinical usefulness of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) compared with histopathological grading, clinical stage and serum prostatic specific antigen (PSA) level in the detection and characterization of prostate cancer. METHODS: Forty-four patients with histologically proven prostate cancer and five control subjects with benign prostatic hyperplasia (BPH) were prospectively investigated with FDG-PET prior to treatment. RESULTS: By visual inspection, FDG accumulation was positive in 28 patients with prostate cancer (sensitivity 64%), whereas all were negative in the control group. FDG-PET in three patients with lymph node metastases did not show any high intrapelvic accumulations corresponding to metastatic sites. Among 12 patients with multiple bone metastases which were detected with 99m-HMDP bone scintigraphy, nine (75%) showed moderate to high FDG accumulation at the sites of bone metastases. Quantitatively, FDG accumulation in prostate cancer was significantly higher than in BPH and there was a tendency for FDG uptake of tumors to be higher with higher histological Gleason grades. Furthermore, FDG uptake in tumors with lymph node and/or bone metastasis was significantly higher than that of localized stages. However, the correlation between PSA and FDG uptake in the prostate cancer was very weak for clinical relevance. CONCLUSIONS: Although FDG-PET was not sensitive enough to detect prostate cancer in clinical use, it is suggested that glucose metabolism in prostate cancer tended to be higher in patients with tumors of advanced stages.

[Clinical significance of prostate specific antigen and gamma-seminoprotein ratio for diagnosing prostate cancer].

It has been reported that prostate specific antigen and gamma-seminoprotein ratio (PSA/gamma-Sm ratio) is an useful means for distinguishing benign prostatic hyperplasia and prostate cancer if serum PSA is measured by Eiken-PSA method. We studied the clinical significance of PSA/gamma-Sm ratio when using Markit-M-PSA method. PSA/gamma-Sm ratio had no superiority over PSA alone for detecting prostate cancer. The present results suggest that the clinical significance of PSA/gamma-Sm ratio can be varied by various PSA-assay kits.

[Fluorodeoxyglucose positron emission tomography in diagnosis of untreated prostate cancer].

Fluorodeoxyglucose positron emission tomography (FDG-PET) has been utilized since glucose metabolism in cancer tissue is considered to relate to its malignant potential. We evaluate the application of FDG-PET to prostate cancer. FDG uptake of cancer tissues was higher with higher Gleason grade, advanced clinical stage and higher serum PSA value than that with lower Gleason grade, localized clinical stage and lower serum PSA value. The measurement of glucose metabolism in the prostate using FDG-PET was suggested to be useful for evaluation of the biological malignant potential of prostate cancer. It may serve as a predictive factor for prognosis and may be useful in determining the effectiveness of hormonal therapy in prostate cancer.

[Treatment of prostate cancer in patients aged 75 or older].

In view of the increasing incidence and mortality rate of prostate cancer in Japan, the management of elderly patients with prostate cancer is an important issue now. We therefore analyzed the clinicopathological features and long-term outcomes of 182 patients with prostate cancer, aged 75 or older, in order to establish the treatment strategy for this age group of patients. There were more patients with advanced disease (stage C-D) than those with localized disease (stage A2-B), and the patients with moderate to poorly differentiated tumors were more numerous than those with well-differentiated tumors. The overall survival curve of the patients with localized prostate cancer was in line with the age-matched expected survival curve, while that with advanced prostate cancer was far below the expected survival curve. These results demonstrated that advanced prostate cancer in elderly patients is as harmful as in younger patients, indicating the necessity for early detection and treatment of prostate cancer among the younger generation. On the other hand, localized prostate cancer in elderly patients should be treated less invasively to maintain their quality of life.

[A collision tumor between squamous cell carcinoma and malignant lymphoma of urinary bladder: a case report].

A 68-year-old-male was admitted to our hospital with the chief complaint of macrohematuria. He was diagnosed with malignant lymphoma at 63 years old. Cystoscopy and computerized tomography revealed a non-papillary and broad based tumor at the anterior wall of the urinary bladder and partial cystectomy was done. Pathological diagnosis was collision tumor between squamous cell carcinoma and malignant lymphoma. To our knowledge, this is the 13th case of collision tumor associated with genitourinary organs in the literature.

Nephrogenic adenoma in a patient with transitional cell carcinoma of the bladder receiving intravesical bacillus Calmette-Guérin.

A 76-year-old-man was admitted to our hospital for a recurrent bladder tumor. He had received intravesical bacillus Calmette-Guérin (BCG) treatment for a transitional cell carcinoma of the bladder. A follow-up cystoscopy revealed a solitary papillary tumor in the left bladder wall. A transurethral cold cup biopsy revealed a nephrogenic adenoma without any evidence of malignant cells. We discuss the pathogenesis of nephrogenic adenoma and suggest that prolonged cystitis caused by intravesical BCG may play an etiological role.

Histologic characteristics of renal cell carcinomas with lymph node metastasis.

BACKGROUND: This study was conducted to determine if there are any specific histologic features that are associated with lymph node metastasis in renal cell carcinoma (RCC). METHODS: TNM classification, histologic grade, mean nuclear volume, cell type, and histologic architecture of the tumors were evaluated in 66 patients who had undergone nephrectomy and lymphadenectomy for RCC. In the 18 patients with positive lymph node metastasis, both primary lesions and metastatic lymph nodes were evaluated. RESULTS: Lymph node status was correlated with primary tumor stage, venous involvement, and distant metastasis. The tumor grade was higher, and the mean nuclear volume was larger, in both primary and metastatic lesions of RCCs with lymph node metastasis than in tumors with no metastasis. In primary lesions of RCCs with lymph node metastasis, clear cell, alveolar, or cystic patterns were observed less frequently, and granular or spindle/pleomorphic cells and papillary or solid patterns, were observed more frequently, as compared to those lesions without metastasis. Comparison between primary and metastatic lesions in individual patients revealed no significant difference in grade or mean nuclear volume. The development of new cell types or histologic architectures, which was not noted in the primary lesions, was also a rare event in the metastatic lesions. CONCLUSION: Several characteristic histologic features, which may reflect the increased metastatic potential of the tumor, were observed in both primary and metastatic lesions in cases of RCC with lymph node metastasis. No substantial difference in histologic features was observed between the primary or metastatic lesions of individual patients.

[Treatment outcome of radical cystectomy during a 10-year period (June 1984-September 1994) at Department of Urology, Fukui Medical School].

The treatment outcome was evaluated in 63 patients with bladder cancer more than 2 years after cystectomy. Cisplatin-based combination chemotherapies were given to 40 patients after the operation as an adjuvant therapy and two patients with T4 or N2 bladder cancer received chemotherapy before the operation as a neoadjuvant therapy. The extent of infiltration of the removed tumors was pTa in 5, pT1 in 18, pT2 in 8, pT3a in 6, pT3b in 17, and pT4 in 9 cases. Regional lymph node metastases were present in 10 cases (16%). Nineteen patients died of tumor recurrences. The 5-year acturial survival rates at each stage were 60% for stage pTa, 78% for stage pT1, 63% for stage pT2, 83% for stage pT3a, 33% for stage pT3b and 38% for stage pT4, respectively. A significant difference (p < 0.05) in survival curve was observed between pT3a and pT3b. The prognosis of patients with tumors extending beyond the bladder muscles is extremely unfavourable, with the exception of bladder cancers infiltrating the neighboring organ (pT4a), the removal of which may result in lasting survival in a part of the cases. Effective adjuvant treatment is required for patients with bladder tumors penetrating the bladder wall.