Biomedical subjects

S Egawa

Publications and source records attributed to S Egawa.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1998

Results of transrectal ultrasound-guided biopsies and clinical significance of Japanese prostate cancer.

BACKGROUND: We review the outcomes of ultrasound-guided biopsy in consecutive patients and assess clinical significance of Japanese prostate cancer. METHODS: Examination was made of 1469 patients subsequent to transrectal ultrasound-guided biopsy of the prostate gland. For 84 patients, two or more sets of ultrasound-guided biopsies were conducted following the initial negative results during this period. Two hundred and thirty-two patients with benign histology at the initial biopsy underwent transurethral resection of the prostate (TURP). The clinical significance of the cancers was assessed based on patient age and calculated tumor volume at diagnosis, assumed cancer volume doubling time and life-expectancy in the Japanese male population. RESULTS: Overall, 327 of the 1469 patients (22.3%) had prostate carcinoma. Positive biopsy rates in patients with PSA 2.0 ng/ml or lower, 2.1-4.0 ng/ml, 4.1-10.0 ng/ml and 10.1 ng/ml or greater were 4.6%, 8.6%, 15.8% and 59.5%, respectively. Of the 232 patients who underwent TURP, 15 (6.5%) had cancer. Of the 84 patients subjected to the multiple sets of biopsies, 19 (22.6%) cancers were detected. Of the 203 cancers without distant metastasis at initial biopsy, 13.3%, 25.1%, 32.5% and 40.4% of tumors for 2-, 3-, 4- and 6-year tumor doubling times gave no indication of clinical significance. Nearly half these patients (43-52%) had clinical stage T1c disease. The estimated proportion of clinically insignificant tumors in repeat biopsy was virtually the same as first set biopsies. CONCLUSIONS: Low PSA was not necessarily an indication of indolent cancer and repeat biopsy did not often demonstrate clinically unimportant cancers. Many patients with stage T1c disease may eventually prove to require no treatment.

Adult↗

PubMed1998

Public awareness and knowledge of prostate cancer in Japan: results of a survey at short-stay examination facilities.

BACKGROUND: This study was undertaken to determine public awareness and knowledge of prostate cancer, which has not been adequately studied in Japan. METHODS: Assessment was made of public awareness and perception of prostate cancer in Japan, based on health examination data for participants in a short-stay physical examination program ("human dry dock"). A multiple-choice, thirty-point questionnaire survey was conducted at 3 "human dry dock" medical facilities situated in urban areas. RESULTS: Many Japanese adults appeared to be inadequately aware of prostate cancer and of the means available for its early detection. One third of the participants were unfamiliar with this malignancy. Logistic regression analysis indicated smoking to be the only covariate associated with lack of knowledge of prostate cancer (P< 0.05). Seventy-one percent of the subjects had heard of digital rectal examination, but only 16% and 8%, respectively, were familiar with the terms transrectal ultrasonography and PSA testing. Japanese people may possibly be less informed about prostate cancer than African-American males. Both "human dry dock" facilities and subject gender were significantly associated with knowledge of digital rectal examination (P< 0.05). Knowledge of transrectal ultrasonography was found to depend on participation in "human dry dock" programs and level of education (P< 0.05). Smoking, participation in "human dry dock" programs under employer direction, and health status were all identified as determinants for knowledge of PSA testing (P< 0.05). CONCLUSION: Educational programs should be established and put into effect to instill adequate awareness of prostate cancer in Japan. In a better-informed society, more effort would be directed toward prevention and thus early stage prostate cancer would be detected more often.

Adult↗

PubMed1998

Preoperative predictors for organ-confined disease in Japanese patients with stage T1c prostate cancer.

BACKGROUND: In order to define the characteristics of patients with clinical stage T1c prostate cancer in Japan, clinicopathologic data obtained from patients treated by radical prostatectomy were reviewed. METHODS: Fifty-four stage T1c cancers were evaluated for tumor volume, Gleason grade, tumor location and pathologic stage from prostatectomy specimens in association with preoperative clinical parameters. RESULTS: The mean tumor volume was 3.94 mL (range, 0.07 to 33.4 mL), and 11 of the 54 tumors had a tumor volume of less than 0.5 mL. Thirty-two tumors (59%) were organ-confined, while 7 (13%) involved the seminal vesicle and/or regional lymph nodes. Multivariate logistic regression analysis of the pretreatment variables, including age, pretreatment PSA level, prostate volume, biopsy grade, and number of cancer-positive cores revealed that the serum PSA level and the number of cancer-positive biopsy cores were independent factors to predict organ-confined tumors (P = 0.036 and 0.044, respectively). For T1c cancer with less than 4 cancer-positive biopsy cores, the sensitivity and specificity for predicting organ-confined tumors were 90% and 70%, with a cut-off value of 17 ng/mL for the serum PSA level. CONCLUSION: The clinicopathologic features of T1c prostate cancer in Japanese patients were similar to those of whites reported elsewhere. Both serum PSA levels and the number of positive biopsy cores may be useful as pretreatment parameters to identify patients with the potential to benefit from radical treatment.

Aged↗

PubMed1998

[Efficacy of transrectal ultrasonography in staging prostate cancer].

Clinical staging can be defined as the attempt to determine the pathologic extent of cancer by clinical tests. Accurate preoperative assessment is essential for the appropriate selection of therapy and design of treatment for the individual patients with prostate cancer. Transrectal ultrasonography (TRUS) was initially applied clinically in 1971. It is currently considered an essential tool in the management patients with prostatic disease. More importantly, ultrasound guidance allows accurate sampling of prostatic tissue. However, the role of sonographic imaging itself in diagnosing of tumor extent remains uncertain. In this chapter we will assess critically the present role of ultrasound in staging prostate cancer based on currently available criteria.

Humans↗

PubMed1998

[Impact of life expectancy on the clinical significance and curability of prostate cancer].

Theoretical projected prostate cancer volume at the time of expected death was determined based on patient age and index cancer volume at diagnosis, assumed cancer volume doubling time and life expectancy of Japanese male population. Clinically insignificant cancer in 104 prostatectomy specimens was found to occur at 4.8, 10.6, 15.4 and 26.9% for tumor doubling times of 2, 3, 4 and 6 years, respectively. Assuming a 2-year doubling time with clinically insignificant cancer excluded, only 36.4% of significant cancers could be considered potentially curable and with a 3-year doubling time, 32.3%. For 4- and 6-year doubling times, only 30.7% and 25.0% of the clinically significant cancers were potentially curable, respectively. Patient life expectancy and tumor doubling time significantly determine the outcome of treatment for prostate cancer especially in elderly males with higher risk of mortality.

Aged↗

PubMed1998

[Concentrations of free form and complex form of prostate-specific antigen in serum of alpha 2 macroglobulin deficient patients with prostatic carcinoma].

Prostate-specific antigen (PSA) is present in blood in free form as well as in complex form with various protease inhibitors such as alpha 2 macroglobulin (alpha 2M) and alpha 1 antichymotrypsin (alpha 1 ACT). We had found that alpha 2M is deficient (below approximately 40 mg/dl) in some patients with prostatic carcinoma. Therefore, we investigated the levels of free and complex form of PSA in patients with prostatic disease and obtained the following results. The HPLC study showed that total (free plus complex) PSA level was much higher in the alpha 2M deficient patients with prostatic carcinoma stage D (n = 7, range 1,530-14,746 ng/ml, median value 6,800 ng/ml) than in the non-deficient patients with stage D (n = 16, range 121.6-4,210 ng/ml, median value 851 ng/ml). In the deficient patients, the complex of PSA with alpha 1 ACT increased extraordinarily while free PSA increased to only some extent. In the more severe cases of prostatic carcinoma, the ratio (complex/total PSA) was higher while the ratio (free/total PSA) was lower. The SDS-PAGE Western blotting showed that complex PSA increased extraordinarily and free PSA increased in sera of the deficient patients which was consistent with the HPLC results. Many bands appeared on the blotting at the positions smaller than alpha 2M molecule, which indicated that many fragments of alpha 2M were present in their sera. These bands were more intense than the bands with sera of controls or benign prostatic hypertrophy. The alpha 2M deficiency may be due to the rapid disappearance of the complex with PSA or any other prostate-originated proteases. The complex may undergo accelerated degradation or catabolism of alpha 2M.

Aged↗

PubMed1998

[Clinical utility of the free prostate specific antigen (PSA), alpha 1-antichymotrypsin-complexed PSA, and free/total PSA ratio using the specific and sensitive enzyme-linked immunosorbent assay "E-plate EIKEN PSA"].

We studied the clinical significance of serum prostate specific antigen (PSA) ratio: free-PSA/total-PSA and free-PSA/complex-PSA to discriminate between prostate cancer (PC) and prostate benign disease (non-PCa) by using total-PSA, alpha 1-antichymotrypsin complexed (complex)-PSA and free-PSA enzyme-linked immunosorbent assay (ELISA) kits newly developed at EIKEN Chemical Co, Ltd. Fre-PSA and complex-PSA ELISA kits demonstrated high sensitivity and specificity. Total-PSA ELISA kit also demonstrated equimolarity for free-PSA and complex-PSA. On the total-PSA range of 4-10 ng/ml, free-PSA/total-PSA% (f/t%) and free-PSA/complex-PSA% (f/c%) were very useful to discriminate between PCa and non-PCa by receiver operating characteristic curve analysis as well as PSA density (PSA-D) but not free-PSA level. F/t% and f/c% were even useful to discriminate early stage PCa (i.e. A1 or B0) from non-PCa by the Mann-Whitney U-test.

Enzyme-Linked Immunosorbent Assay↗

PubMed1997

Detection of prostate carcinoma using prostate specific antigen, its density, and the density of the transition zone in Japanese men with intermediate serum prostate specific antigen concentrations.

BACKGROUND: This study was undertaken to determine whether the prostate specific antigen (PSA) density (PSAD) and PSAD of the transition zone (PSADT) are useful in the detection of prostate carcinoma in Japanese men with intermediate levels of serum PSA. METHODS: Two hundred and eighty-seven Japanese men with intermediate serum PSA levels (2.1 ng/mL to 10 ng/mL) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and systematic biopsy under TRUS guidance. The volume of the transition zone was also measured by TRUS in 134 patients. The PSAD and PSADT were determined for each patient, and their relationship to prostate carcinoma detection was examined. RESULTS: Prostate carcinoma was detected in 30 of 287 patients (10.5%). Although the serum PSA levels were similar in patients with benign and malignant prostate disease (P = 0.541), the prostate volume (P 0.0009) and PSAD (P < 0.0001) differed significantly in the two groups; in the patients with prostate carcinoma, the prostate volume was smaller, and the PSAD higher, than in the patients with benign disease. At the PSAD cutoff value of 0.18 ng/mL/cm3 or greater, the sensitivity was 70% and the specificity was 67% for the diagnosis of prostate carcinoma. The PSAD was found to be significantly better in the differentiation between benign and malignant prostate disease than the serum PSA in the receiver operating characteristic analyses (P = 0.045). However, the receiver operating characteristic curve for PSAD was not significantly different compared with that for PSA in the men with negative digital rectal examination findings. Prostate carcinoma was detected in 9.0% (12 of 134) of the patients who underwent PSADT determination. Receiver operating characteristic analyses showed that PSADT was not superior to PSA in the detection of prostate carcinoma. CONCLUSIONS: In Japanese men with intermediate serum PSA concentrations, PSAD offers additional information useful in the detection of prostate carcinoma, but PSADT does not. Although use of PSAD may decrease the number of unnecessary biopsies, a significant number of prostate carcinomas may be overlooked. Therefore, the authors recommend that serum PSA levels continue to be used as an indicator for biopsy in Japanese men.

Adult↗

PubMed1997

The ratio of free to total serum prostate specific antigen and its use in differential diagnosis of prostate carcinoma in Japan.

BACKGROUND: To improve the clinical usefulness of prostate specific antigen (PSA), unique methods have been proposed. The percentage of free PSA in serum facilitates the distinction between benign histologic conditions and prostate carcinoma while retaining high sensitivity. METHODS: Using monoclonal antibodies, an AIA total PSA assay system was established that recognized PSA equally in free or complex form. The clinical usefulness of the ratio of two different molecular forms of PSA was investigated using 268 archival serum samples. RESULTS: Men with prostate carcinoma had significantly lower ratios of free to total PSA than those with benign prostatic hyperplasia (BPH) (P = 0.0001). At total PSA levels between 2.1 and 10 ng/mL, medians of total PSA were not significantly different between men with prostate carcinoma and men with BPH. Differences in median percentages of free PSA for these two groups were statistically significant (P = 0.0001). The ratio of free to total PSA was useful for identifying prostate carcinoma in palpably benign glands with total PSA of 2.1-10 ng/mL (P = 0.0001), whereas total PSA was not useful for such identification. When calculated for low total PSA levels between 2.1 and 4 ng/mL, sensitivity and specificity were 91.7% and 72.2%, respectively, with a cutoff value of 17%. This ratio of free to total PSA was as useful as PSA density in receiver-operating curve analysis. CONCLUSIONS: The use of the ratio of free to total PSA renders total PSA of greater use of distinguishing prostate carcinoma and is applicable to patients with low total PSA. Elderly men with a clinical diagnosis of BPH who are scheduled for surgery may benefit from the determination of this ratio.

Aged↗

PubMed1997

Treatment of minute medullary thyroid carcinoma in multiple endocrine neoplasia 2A families first diagnosed by DNA analysis of RET proto-oncogene mutations: a case report.

Multiple endocrine neoplasia (MEN) 2A is an inherited disease characterized by the development of medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. It has recently been shown to be associated with germ-line mutations in the RET proto-oncogene. We describe a 21-year-old man from a MEN 2A family who was found by DNA analysis to be a gene carrier of MEN 2A and then was diagnosed, using a stimulated calcitonin test, as having presymptomatic medullary thyroid carcinoma. His morbidity seems to have been cured by total thyroidectomy as postoperative calcitonin levels after stimulation are normal. It is concluded that direct genetic analysis for mutations in the RET proto-oncogene should be the diagnostic test of choice for identifying family members at risk for MEN 2A.

Adrenal Gland Neoplasms↗

PubMed1997

Urinary continence following radical prostatectomy.

An examination was made of pre- and postoperative variables for predicting urinary continence following radical prostatectomy in 94 consecutive patients. Postoperative recovery of urinary continence continued for up to 18 months, when it plateaued. No pads were required in 73.0% of the patients at 18 months. The interval until recovery of urinary continence following surgery averaged 4.0 +/- 3.3 months. Clinical stage, pathologic stage, tumor grade, tumor volume, preservation of neurovascular bundles, methods of bladder neck reconstruction, internal urethrotomy for anastomotic stricture and postoperative adjuvant external beam radiation therapy provided no indication of postoperative urinary incontinence. Preoperative endocrine therapy, preoperative prostate-specific antigen level of > or = 10.0 ng/ml and age < 70 years at the time of surgery were all associated with a greater probability of urinary incontinence. Multiple factors are involved in the etiology of postprostatectomy urinary incontinence. In patients who had undergone surgery because of local progression following endocrine therapy associated with a high serum prostate-specific antigen level, a significantly inferior outcome was noted. Stricter criteria for indicating radical prostatectomy in patients with prostate cancer are needed. Surgical techniques should also be improved for better overall continence.

Adult↗

PubMed1997

A nationwide clinical survey of patients with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma in Japan.

MEN (multiple endocrine neoplasia) type 2 syndrome is an inherited disease characterized by medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism and/or developmental anomalies. Germ-line mutations of the RET proto-oncogene have recently been identified as the underlying cause of the syndrome. Accordingly, several investigators have advocated prophylactic total thyroidectomy for medullary thyroid carcinoma at an early age in MEN 2 gene carriers identified by DNA analysis. Before applying this strategy in Japan, the biological behavior of each category of tumor in MEN 2 syndrome, and medullary thyroid carcinoma in particular, should be well understood. We conducted a nationwide questionnaire survey to clarify the clinicopathological features of MEN 2 in Japan, obtaining data for 230 patients diagnosed as having MEN 2. They included 84 males and 146 females, with a median age of 37.5 years (range 5-83). Patients were categorized as 179 with MEN 2A, 17 with MEN 2B, 12 with familial medullary thyroid carcinoma and 22 'other'. Medullary thyroid carcinoma, pheochromocytoma and parathyroid lesions occurred in 224 (97%), 132 (57%) and 25 (11%) patients respectively. Twelve patients (5.2%) died of medullary thyroid carcinoma and 11 patients died of other or unknown causes. Of 163 patients for whom follow-up data were obtained, 82 (50%) experienced recurrences of medullary thyroid carcinoma, including symptomatic recurrent tumors in 24 patients and elevated calcitonin levels alone in 54. In the era of RET mutational analysis for screening relatives of patients with MEN 2, these data provide useful information about surgical management for patients with MEN 2 in Japan.

Adolescent↗

PubMed1997

Impact of life expectancy and tumor doubling time on the clinical significance of prostate cancer in Japan.

Theoretical projected prostate cancer volume at the time of expected death was determined based on patient age and index cancer volume at diagnosis, assumed cancer volume doubling time and life expectancy of the Japanese male population. Based on the data obtained, evaluation was made of the results for 104 consecutive radical prostatectomy cases with no prior treatment. Clinically insignificant cancer in 104 prostatectomy specimens was found to occur at 4.8, 10.6, 15.4 and 26.9% for tumor doubling times of 2, 3, 4 and 6 years, respectively. Assuming a 2-year doubling time with clinically insignificant cancer excluded, only 36.4% of significant cancers could be considered potentially curable and with a 3-year doubling time, 32.3%. For 4- and 6-year doubling times, only 30.7 and 25.0% of the clinically insignificant cancers were potentially curable, respectively. Approximately half of these insignificant cancers were clinically stage T1c disease. In all stage T1c cases, 8.8-47.1% was considered insignificant, depending on tumor doubling time. Patient life expectancy and tumor doubling time significantly determine the outcome of treatment for prostate cancer, especially in elderly males with higher risk of mortality. The outcome of radical prostatectomy is less satisfactory with these factors taken into consideration. Many patients with stage T1c disease may eventually prove to require no treatment.

Aged↗