Biomedical subjects

S Egawa

Publications and source records attributed to S Egawa.

At least 19 recordsLinked to original sources

PubMed1999

Observations of prostate specific antigen doubling time in Japanese patients with nonmetastatic prostate carcinoma.

BACKGROUND: To understand better the natural history and biology of prostate carcinoma occurring in Japanese patients, the authors attempted to define changes with time in prostate specific antigen (PSA) measurements in 48 men with clinically resectable T1-T3 nonmetastatic disease. METHODS: The authors analyzed PSA changes prospectively in prostate carcinoma patients who were managed by watchful waiting. PSA doubling time was calculated by linear regression. These values and their distribution were compared with clinical parameters and with published series of prostate carcinoma patients. RESULTS: The mean age of the 48 patients at the time of diagnosis was 74.2 years. The median follow-up from the time of diagnosis was 24.0 months. The median PSA doubling time was 35.7 months. In 27.1% of patients, there was no increase in the PSA level over the observation period. A rapid rise in PSA (doubling time of <2 years) was observed in 29.2% of patients. These results in Japanese patients are virtually the same as those reported in Western countries. There was no statistically significant relation between calculated PSA doubling time and clinical disease stage, tumor grade, PSA level at the time of diagnosis, probability of extraprostatic disease, patient age at diagnosis, or prostate volume (P > 0.05). CONCLUSIONS: Prostate carcinoma may not differ significantly by race once it becomes clinically manifest. The magnitude of positive changes in PSA over a given period of observation may not be helpful in determining the need for therapy. The previously reported incidence of clinically insignificant prostate carcinoma, which primarily was based on pathologic findings in surgical specimens, may have been an underestimation.

Aged↗

PubMed1999

Controlling tumor angiogenesis and metastasis of C26 murine colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models.

Experimental evidence has directly implicated matrix metalloproteinases (MMPs) in the remodeling of the stromal tissue surrounding tumors. Thus, MMP inhibitors could limit the expansion of both neoplastic cell compartment and endothelial cell compartment of a tumor. Much of the work on the role of MMP inhibitors has concentrated on their inhibitory effects on tumor cell invasion. We have examined the effects of a new MMP inhibitor, KB-R7785 (acting on MMP-1, MMP-3, and MMP-9), on tumor angiogenesis and metastasis of murine colon adenocarcinoma (C-26) in two tumor models in BALB/c mice (transparent chamber model and lung colonization model). KB-R7785 has not shown inhibitory effects on in vitro growth of either C-26 or KOP2.16 murine endothelial cells. In vivo, KB-R7785 administrated twice daily for 15 days (100 mg/kg, i.p.), starting the day of tumor inoculation (5 x 10(5) C26 cells) in transparent chamber, has resulted in 88.2% suppression of tumor growth, compared with that in vehicle-administered mice (controls). Tumors grown in controls have doubled their area in 3.3 days, whereas those treated by KB-R7785 progressed almost four times slower (tumor area doubling time, 12 days). KB-R7785 rendered centrally avascular tumors with only a rim of peripheral neovasculature, which had significant lower functional vascular density and vascular area than the corresponding parameters in control tumors 10 days after inoculation [79.9+/-6.7 cm/cm2 versus 164.1+/-10.1 cm/cm2 (P < 0.01) and 19.8+/-1.5% versus 42.6+/-2.7% (P < 0.01), respectively]. In the lung colonization model (tail vein inoculation of 5 x 10(5) C-26 cells), administration of KB-R7785 (100 mg/kg, i.p.) twice daily for 20 days has reduced the number of surface metastasis by 85.8% and abolished the tumor burden, as compared with controls. The few metastatic colonies found in the lungs of KB-R7785 treated mice appeared to be dormant (i.e., staining with von Willebrand factor antibody revealed few, if any, positive cells within the metastatic foci from MMP inhibitor-treated lungs, whereas terminal deoxynucleotidyl transferase-mediated nick end labeling showed a 4-fold increase in the rate of tumor cell apoptosis compared with controls. The fact that KB-R7785 interferes with early steps of angiogenesis and cancer spread suggests that MMP inhibitors may control both primary and secondary tumor growths by limiting the expansion of endothelial cells, as well as cancer cells, composing the tumors.

Adenocarcinoma↗

PubMed1999

Limited suppression of prostate-specific antigen after salvage radiotherapy for its isolated elevation after radical prostatectomy.

OBJECTIVES: To investigate the clinical outcome and degree of prostate-specific antigen (PSA) suppression after salvage radiotherapy performed because of isolated PSA elevation after radical prostatectomy. METHODS: We examined the outcomes of 32 patients who underwent radiotherapy after radical prostatectomy. Hypersensitive, as well as conventional, PSA assays were used to measure PSA levels after irradiation. RESULTS: Of 125 patients who underwent radical prostatectomy for clinically resectable prostate cancer, 42 (33.6%) developed detectable PSA an average of 13.5 months postoperatively. Thirty-two patients underwent salvage radiotherapy. In 13 patients (40.6%), PSA became undetectable (less than 0.1 ng/mL) at a mean of 1.2 months. Two of these patients later developed detectable PSA within 1 2 months. Of 22 patients who had at least 12 months of follow-up, 8 had a durable PSA response. Of 13 patients who attained an undetectable PSA postoperatively and then showed a delayed progressive increase, 7 exhibited a durable response lasting for more than the 12 months after irradiation. By contrast, only 1 of 9 patients with persistently elevated postoperative PSA showed undetectable levels after irradiation. Frozen sera from the 8 patients with a durable response to irradiation were available to measure levels less than 0.1 ng/mL by hypersensitive assay. The mean value was 0.035 ng/mL at an average of 26.9 months after irradiation. Only 3 patients had levels less than 0.01 ng/mL. CONCLUSIONS: Although radiotherapy may be beneficial in a small number of patients, many patients continue to have measurable levels of PSA (more than 0.01 ng/mL) after irradiation. Our results suggest that this treatment in its current form is inadequate to eradicate residual carcinoma.

Aged↗

PubMed1999

[Indication of repeat prostatic biopsy following previous negative findings].

BACKGROUND: Many men with clinically suspicious findings would not be diagnosed to have prostate cancer. Establishing criteria for indicating repeat biopsy is imperative for early detection of prostate cancer. METHODS: Eighty-one patients underwent repeat prostatic biopsies under sonographic guidance at Kitasato University Hospital between March 1992 and October 1996. Clinicopathological parameters such as age, prostate specific antigen (PSA), PSA adjusted for transition zone volume (PSAT), PSA density (PSAD), PSA velocity, transition zone volume, prostatic volume, rectal findings, ultrasound findings and initial biopsy histology were compared with the results of repeat biopsy for searching for possible predictors of positive biopsy. RESULTS: Cancer was confirmed in 14 patients (17.3%), 10 patients by the second biopsy (15.4%, 10/65) and 4 patients by the third biopsy (28.6%, 4/14). No cancer was found at the 4th or more biopsies. Twelve (85.7%) of these patients had prostatic volume less than 40 cm3. Univariate analysis indicated PSAT, PSAD, transition zone volume and prostatic volume to be more frequent in men with positive biopsies (p < 0.05). But multivariate logistic regression analysis failed to identify any significant predictors of positive results in repeat biopsies. CONCLUSIONS: No clinicopathological parameters could reliably predict repeat biopsy findings. One or 2 additional sets of biopsies is recommended based on clinical judgement (symptoms, life expectancy, small glands < or = 40 cm3 etc.) for the purpose of early detection of prostate cancer in patients with previously negative biopsy but still with suspicious findings in consideration of approximately 20% false negative rates by the initial biopsy.

Aged↗

PubMed1999

[Histological characteristics and clinical significance of Japanese prostate cancer with low levels of prostate specific antigen of 4.0 ng/ml or lower].

PURPOSE: They set a normal limit of prostate specific antigen (PSA) to 4.0 ng/ml in Tandem R assay at most institutions. We investigated clinical and histological characteristics of prostate cancer based on whole mount step-section histology of radical prostatectomy specimens, and taking notice of Japanese prostate cancer whose levels of PSA are less than 4.0 ng/ml in normal levels. MATERIALS AND METHODS: One hundred and twenty-two patients underwent radical prostatectomy for clinically resectable prostate cancer at University Hospital from February 1992 to April 1997. Clinicopathological findings were stratified according to the preoperative PSA levels in 111 patients without preoperative endocrine therapy. Immunohistochemical study for PSA was conducted in 7 randomly selected patients. RESULTS: Of the patients 22 (19.8%) had normal (4.0 ng/ml or lower) preoperative serum PSA. Mean tumor volume in this PSA range was 1.5 cm3 with one pT 0 case included. Pathologically organ confined, potentially curable disease (< pT 3) was found in 17 (77.3%) patients and extracapsular extension and seminal vesicle invasion in 5 (23.8%), respectively. No patients had positive pelvic lymph nodes. Well differentiated tumors of Gleason scores 2-4 were found in 9 (40.9%) of the patients, moderately differentiated tumors (Gleason scores 5, 6) in 5 (22.7%) and poorly differentiated histology (Gleason scores 7-10) in 7 (31.8%). Sixteen (72.7%) patients had clinically significant tumors (> 0.5 cm3, Gleason score > or = 7). All 7 patients had positive staining for PSA, but its intensity did not correlate with serum PSA levels. CONCLUSIONS: Many prostate cancers found in surgical specimens were clinically significant despite the low levels of PSA and potentially curable by definitive treatment. Age, co-morbidity and other clinicopathological variables as well as PSA levels should all be taken into account when treatment options are discussed.

Aged↗

PubMed1999

[Usefulness of power Doppler sonography for the assessment of subpleural lesions].

We investigated the usefulness of color Doppler power mode imaging for the assessment of subpleural lesions in 48 patients (27 with pneumonia, 4 with pulmonary abscesses, 12 with primary lung cancer, and 5 with metastatic lung cancer). We classified the patterns obtained by color flow imaging of subpleural lesions into six groups: type 0, no color flow; type I, spotty color flow; type II, linear color flow; type III, branchy color flow; and type IV, tortuous color flow, with type IV-A, for partial tortuous flow and type IV-B, for general tortuous flow. The color Doppler power mode proved better than velocity mode in terms of ability to generate clear color flow patterns. Color flow patterns obtained in power mode on the patients with pneumonia differed significantly from the patterns obtained on the lung cancer patients. Although the color flow patterns observed in power mode differed significantly for the benign and malignant groups, no statistically significant differences were observed in velocity mode. These findings illustrated the usefulness of color Doppler power mode imaging as a means of diagnosing benign and malignant subpleural lesions.

Adolescent↗

PubMed1999

[Therapeutic strategy for the recurrence of pancreatic cancer following pancreatectomy].

It is well-known that the patients with pancreatic cancer are vulnerable for recurrence such as local relapse and liver metastasis after surgical resection. We revealed that a patient with local relapse without liver metastasis showed better prognosis as compared with a patient having liver metastasis. We usually adapt further therapeutic intervention for local recurrence using external radiation therapy accompanied with 5FU infusion as a radiosensitizer, if the patient is not revealed with liver metastasis. On the other hand, there is no effective intervention for liver metastasis accompanying pancreatic cancer, as small lesions of multiple liver metastases progress rapidly. We insert the tip of catheter in proper hepatic artery in order to infuse MMC once a week at outpatient clinic. However, we were not yet able to evaluate the effect of arterial infusion therapy.

Infusions, Intra-Arterial↗

PubMed1998

Hereditary dentatorubral-pallidoluysian atrophy: ubiquitinated filamentous inclusions in the cerebellar dentate nucleus neurons.

We examined the cerebellar dentate nucleus (CDN) in 16 patients with hereditary dentatorubral-pallidoluysian atrophy (DRPLA), one of the neurodegenerative diseases caused by expansion of a CAG repeat encoding a polyglutamine tract in the disease protein. In all patients, some CDN neurons were found to contain ubiquitinated filamentous inclusions in their cytoplasm. On hematoxylin and eosin preparations, these filamentous inclusions were eosinophilic, basophilic or amphophilic, and were often found in areas of pale cytoplasm. Electron microscopy revealed that they consisted of bundles of filaments that were somewhat thicker than neurofilaments. These features of the present inclusions were indistinguishable from those of skein-like inclusions (SLI) previously described in the lower motor neurons in sporadic amyotrophic lateral sclerosis. We conclude that SLI can also occur in the CDN in DRPLA and believe that they reflect a characteristic pathological process in this disease.

Adolescent↗

PubMed1998

Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain.

We examined the brains and spinal cords of seven patients with clinicopathologically and genetically confirmed hereditary dentatorubral-pallidoluysian atrophy (DRPLA) using an antibody against ubiquitin, and found small, round immunoreactive intranuclear inclusions in both neurons and glial cells in various brain regions. Ubiquitinated neuronal intranuclear inclusions (uNIIs) were consistently found in the striatum, the pontine nuclei, the inferior olivary complex, the cerebellar cortex and the dentate nucleus. Ubiquitinated glial intranuclear inclusions (uGIIs) were found less frequently than uNIIs. Most of the inclusion-bearing nuclei were of an astrocytic nature. Immunostaining with an antibody against DRPLA protein revealed similar immunoreactive neuronal and glial intranuclear inclusions, but in much smaller in numbers compared with uNIIs and uGIIs. Electron microscopy showed that such inclusions were composed of granular and filamentous structures. These findings strongly suggest that, in DRPLA, the occurrence of uNIIs and uGIIs is directly related to the causative gene abnormality (an expanded CAG repeat encoding polyglutamine), that neurons are affected much more widely than previously recognized and that glial cells are also involved in the disease process.

Adult↗

PubMed1998

Intraoperative radiotherapy for pancreatic adenocarcinoma.

Intraoperative radiotherapy (IORT) is an innovative treatment approach for cancer of the pancreas. The common causes of treatment failure in pancreatic cancer are regional recurrence and distant metastasis. While at present the benefit of IORT in unresectable pancreatic cancer is still controversial and awaits further prospective trials for its clarification, the experience gathered over a period of 30 years with IORT for pancreatic cancer does suggest that IORT should be part of the adjuvant therapy of surgical resection. A combination with pre- or postoperative external beam radiotherapy and chemotherapy may be beneficial for both resectable and unresectable patients. IORT was shown to be a relatively safe intervention and it notably improved the quality of life of patients with locally advanced pancreatic carcinomas by alleviating their pain. Here, we summarize and discuss the experience reported to date and present our historical analysis of IORT for pancreatic cancer.

Adenocarcinoma↗

PubMed1998

Current and future trends in interventional therapy for benign prostatic hyperplasia in Japan.

PURPOSE: Procedures of Japanese urologists of interventional therapy for benign prostatic hyperplasia (BPH) should be defined for resource economy and policy establishment. MATERIALS AND METHODS: A questionnaire was mailed to the urology departments of 80 medical schools in Japan for clarification of surgical procedures presently in use for treating bladder outlet obstruction due to BPH. Prospects for the next 5 years (year 2002) were also requested. RESULTS: We received 76 questionnaire responses from medical school urology facilities (95%) by the end of January 1997. Standard transurethral resection of the prostate gland is and will continue to be the most common surgical procedure. Open adenectomy is the first choice for large glands but may be replaced by other interventional procedures. Laser prostatectomy and transurethral electrovaporization will be used more often for treating all severities of BPH. CONCLUSIONS: Even with increasing interest in new techniques, transurethral resection of the prostate will continue to serve as the standard therapy for BPH during the next 5 years. Transurethral electrovaporization may become established in the near future.

Humans↗

PubMed1998

Clinical outcome of high-intensity focused ultrasound for treating benign prostatic hyperplasia: preliminary report.

OBJECTIVES: To preliminarily summarize the clinical outcomes of the transrectal high-intensity focused ultrasound procedure using the prototype Sonablate (HIFU1) and the new Sonablate-200 (HIFU2) for treating symptomatic benign prostatic hyperplasia. METHODS: We treated 35 and 22 patients with HIFU1 and HIFU2, respectively. Preoperative and postoperative evaluations were made using the International Prostate Symptom Score (IPSS), quality of life (QOL) data, and the results of uroflowmetry and transrectal ultrasound, and any complications were noted. RESULTS: IPSS and QOL scores showed significant improvement after using both HIFU1 and HIFU2 at 3, 6, and 12 months, postoperatively (P < 0.0001 to < 0.01; Wilcoxon signed-ranks test). Maximum flow rate (8.9 to 15.5 mL/s, P < 0.001) and prostatic volume (32.2 to 22.8 mL, P < 0.01) were significantly improved at 12 months postoperatively in patients who underwent HIFU2 treatment but not in patients who underwent HIFU1. Two hematospermia and one gross hematuria in patients treated with HIFU1 and one epididymitis in a patient treated with HIFU2 were seen but no severe complications were noted. CONCLUSIONS: Focused ultrasound is an effective new technology by which tissue can be destroyed at a site distant from the source of energy without damaging surrounding tissue. The clinical efficacy of HIFU2 was superior to that of the prototype HIFU1.

Aged↗

PubMed1998

Inadequacy of free prostate-specific antigen parameters in the prediction of pathologic extent of prostate cancer in Japanese men.

OBJECTIVES: To evaluate free prostate-specific antigen (PSA) and free to total PSA ratio as predictors of pathologic extent in Japanese patients with prostate cancer. METHODS: By TOSOH assay, pretreatment serum serologic markers of free PSA, total PSA, free to total PSA ratio, and PSA density (PSAD) were determined for 108 patients subsequent to radical prostatectomy for resectable prostate cancer. Serum values for these markers were compared with pathologic findings and tumor volume on the basis of pathologic assessment of whole mount section histology. RESULTS: Mean total PSA, free PSA, free to total PSA ratio, and PSAD significantly differed for pathologically confined (pT2 or lower) and advanced (pT3 or higher) cancers (P < 0.05). Total PSA, free PSA, and PSAD provided indication of seminal vesicle involvement, surgical margin status, nodal involvement, and total tumor volume (P < 0.05). Free PSA was more closely correlated with total tumor volume than the free to total PSA ratio; this ratio was not correlated with total tumor volume or specimen Gleason score. Free PSA and free to total PSA ratio were not found to be any more useful than total PSA and PSAD for predicting pT3 disease by receiver operating characteristic curve analysis. Multivariate logistic regression analysis and log likelihood ratio test results indicated little additional value of these parameters for predicting pT3 disease. CONCLUSIONS: Contrary to previous reports, free PSA and the free to total PSA ratio are of little use subsequent to the diagnosis of prostate cancer.

Adult↗

PubMed1998

Improved predictability of extracapsular extension and seminal vesicle involvement based on clinical and biopsy findings in prostate cancer in Japanese men.

OBJECTIVES: The accurate preoperative prediction of the extent of cancer by pathologic examination is essential for choosing the optimal treatment for patients with prostate cancer. Currently available clinical staging methods are not adequate and more precise staging is required. METHODS: Using the log likelihood ratio test and receiver operating characteristic (ROC) curve analysis, preoperative variables, including biopsy pathologic findings, were assessed for predicting final pathologic stage in prostate cancer. A multivariate model for predicting disease organ confinement status was established for easy clinical use. RESULTS: The use of the number of cores with cancer and maximum cancer length in conjunction with the three variables (prostate-specific antigen, clinical stage, and biopsy Gleason score) was found to significantly improve predictability of extracapsular extension and seminal vesicle involvement in clinically resectable (n = 96) and localized prostate cancers (n = 81) (P < 0.05). Areas under ROC curves for the above two parameter sets (five- versus three-variable model) were 0.8395 and 0.7109, respectively, for capacity for extracapsular extension prediction in clinically localized cancer. These values for seminal vesicle involvement were 0.7861 and 0.6927, respectively. The logistic model gave positive and negative predictive values of 73% and 78%, and 64% and 83%, respectively, for extracapsular extension and seminal vesicle involvement in clinically localized cancer at a predicted probability of 0.5 or greater. CONCLUSIONS: The present method may be used to predict non-organ-confined prostate cancer with greater accuracy than the previously reported model using three variables.

Aged↗

PubMed1998

Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.

To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.

Animals↗

PubMed1998

Zonal biopsy in the detection of prostate cancer in Japanese men.

To reduce sampling error as much as possible in the detection of prostate cancer, extensive transition zone sampling, in addition to the standard sextant random systematic biopsies, has been proposed. Improved biopsy techniques should make possible earlier and more effective detection of prostate cancer in a population where the incidence is low. Evaluation of such biopsies for elderly Japanese males is thus required. A total of 344 Japanese patients participated in this study. They underwent two transition zone biopsies in addition to systematic biopsy. Fifty-five of the 344 patients (16.0%) had cancer. Both biopsies were positive in 33 patients (60.0%), the standard systematic sextant biopsy alone demonstrated cancer in further 20 (36.4%) and the transition zone biopsy alone was positive in two others (3.6%). The two patients with cancer only in the transition zone biopsy cores had palpable abnormality and elevated prostate specific antigen. None of those with palpably benign glands or those with prior negative biopsies had cancer in the transition zone. Two additional cores from the transition zone led to no increase in morbidity of biopsy. Transition zone biopsy would not significantly contribute to the detection of prostate cancer in the present Japanese elderly male population. Though possibly of some value for certain patients, this biopsy does not warrant routine use.

Adult↗

PubMed1998

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗

PubMed1998

Significance of free to total PSA ratio in men with slightly elevated serum PSA levels: a cooperative study.

BACKGROUND: The ratio of free PSA in total PSA (f/t) has been reported to improve the diagnostic accuracy of prostate cancer in the group with slightly elevated serum PSA values. In Japanese cases, the clinical significance of f/t is still controversial. METHODS: The diagnostic significance of f/t in serum for prostate cancer was evaluated in a cooperative study. A total of 77 cases with prostate cancer and 224 with non-prostate cancer showing less than 20 ng/ml of total PSA were evaluated. RESULTS: Serum total and free PSA values were not affected by storage at 25 degrees C for 2 days. The determination of f/t was useful in the cases with a serum total PSA of 5.1-10 ng/ml; the specificity was 60% with a sensitivity of 90% at an f/t of 0.148. The positive predictive value for diagnosis of prostate cancer also increased to 54% from 34% of that in total PSA alone. In the range of 4.1-10 ng/ml, the cut-off value of f/t was 0.155 for obtaining relatively high specificity; sensitivity was 85% and specificity was 56.5%. CONCLUSIONS: Thus, the determination of f/t was considered to be an effective tool for discriminating the non-prostate cancer cases from those of prostate cancer.

Humans↗