Evaluation of myocardial sympathetic nerve function in patients with mitral valve prolapse using iodine-123-metaiodobenzylguanidine myocardial scintigraphy.

Mitral valve prolapse (MVP) is closely related to myocardial sympathetic nerve function. This study evaluated the presence of impaired myocardial sympathetic nerve function by Iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in ten patients with MVP. For comparison, 15 healthy subjects without heart disease were investigated (control group). Single photon emission computed tomography (SPECT) and anterior planar myocardial scintigraphy were performed 15 min (initial images) and 3 hours (delayed images) after injection of MIBG (111 MBq). The location and degrees of reduced tracer uptake were evaluated. Myocardial MIBG uptake was quantified by uptake ratio of the heart (H) to upper mediastinum (M) on the anterior planar images (H/M). Percentage washout of MIBG in nine sectors of all oblique slices along the short-axis was calculated. The washout rates were higher at the inferoposterior and septal segments in patients with anterior leaflet prolapse, and at inferoposterior and lateral segments in patients with posterior leaflet prolapse. The bull's eye map showed increased washout rate in the apical and posteroseptal basal segments. There was no significant difference in the H/M ratio between MVP patients and the control group. These results indicate that MIBG can be used to evaluate localized myocardial sympathetic nerve function in MVP.

[A case of gastrointestinal stromal tumor of rectum, difficult to differentiate from leiomyosarcoma of prostate].

A 70 year-old male was seen at the hospital with the chief complaints of frequent miction and incomplete urinary retention. A hen's egg-sized firm mass was palpable in anterior wall of rectum by digital rectal examination. Intravenous urography showed severe bilateral hydronephroureter. Transrectal ultrasound, CT scan and MRI revealed a mass with 5 cm in diameter between prostate and rectum, and the margin of them were unclear. On needle biopsy of the tumor, leiomyosarcoma of the prostate was suspected. We performed radical cytectomy and created continent urinary reserver. Because the tumor and rectum could not be lysed, part of the rectum was resected. Histological examination showed gastrointestinal stromal tumor (GIST) of rectum. GIST of rectum is a rare entity, and in case of contact with the prostate, it is difficult to differentiate from leiomyosarcoma of prostate.

Clinical characteristics of perioperative coronary spasm: reviews of 115 case reports in Japan.

PURPOSE: Factors affecting perioperative development of coronary spasm have not been elucidated. A number of case reports describing perioperative coronary spasm have appeared in Japanese anesthesia journals, mostly published in Japanese. The purpose of this study was to investigate the contributing factors affecting perioperative coronary artery spasm by reviewing the published articles. METHODS: Reports were identified by using Medline database (1968-1998) or by manually searching nonindexed Japanese journals. The clinical characteristics of perioperative coronary spasm were analyzed in 115 patients who developed coronary artery spasm during the perioperative period. RESULTS: The mean age of the patients was 64 +/- 9 years (range, 36 to 87 years). There were 97 men (84%) and 18 women (16%). Preoperative risk factors included hypertension (27%), angina pectoris (27%), cigarette smoking (13%), and diabetes mellitus (11%). The attack was related to inadequate depth of general anesthesia (23%), use of vasopressors (22%), vagal reflex (19%), administration of drugs other than vasopressors (17%), and epidural block (15%). About 85% of patients showed no ischemic abnormality on the preoperative electrocardiogram, whereas 56% had significant coronary stenosis on postoperative coronary arteriography. Coronary spasm tended to occur in patients under inhalation anesthesia combined with epidural block. Nitrates alleviated the episode in the majority of cases, whereas defibrillation and cardiac massage were required in 19% of patients. No deaths were reported. CONCLUSION: Perioperative coronary spasm is prevalent in elderly male patients with coronary risk factors who undergo abdominal or thoracic surgery under inhalational anesthesia combined with epidural anesthesia. Instability of the autonomic nervous system and/or vascular hyperreactivity may be the underlying pathogenic mechanisms of perioperative coronary spasm.

[Two cases of primary carcinoma developed in a vesical diverticulum treated with ileal neobladder for total bladder replacement].

Two cases of carcinoma developed in vesical diverticulum were encountered. Both these males, the first, 66-year-old and the second case, 68-year-old gentleman, visited our clinic with a complaint of asymptomatic gross hematuria. Total cystectomy was performed, and an ileal neobladder was constructed for total bladder replacement in both two cases. Pathological examination of the first case revealed transitional cell carcinoma, and the second case showed adenocarcinoma mixed with transitional cell carcinoma. Although primary carcinoma developed in vesical diverticulum was initially reported by Williams in 1883, adenocarcinoma is very rare. The diagnosis is often challenging and the prognosis is dire. Both our cases were successfully treated with total cystectomy and an ileal neobladder was constructed for total bladder replacement. Careful management and aggressive therapy for such patients may make even cure possible.

[Clinical study of grade 3, superficial transitional cell carcinoma of the urinary bladder].

PURPOSE: To evaluate the treatment of grade 3 superficial (stage pTa and pT 1) transitional cell carcinoma (T.C.C.) of the urinary bladder, retrospective analysis was performed with special reference to tumor prognostic factors. MATERIALS AND METHODS: From July 1971 to september 1995, 51 cases with grade 3 superficial T.C.C. of the urinary bladder were treated. The survival rates and prognostic factors of these patient were analyzed. RESULTS: Five year survival rate of grade 3, superficial tumors was 92.3% and showed significantly better prognosis compared to patients with pT 2 and pT 3 tumors of grade 3 (p < 0.001). As a initial treatments, transurethral resection (TUR) was conducted in 45 patients (88%). Intravesical recurrence was observed in 20 of 45 patients (44%) and 12 of 20 patients (60%) were recurred within 1 year. Non-recurrent rates of the patients treated with TUR were 69.6% at 1 year, 58.8% at 3 year, 49.7% at 5 year, respectively. No significant differences were noted regarding factors of tumor size, figures and a number of tumor. Of the 51 patients, 10 (19.6%) progressed beyond stage T 2 and 6 died with the disease. Survival rates at 10 years follow up in patients with non-papillary and papillary tumor were 57.1% and 97.8%, respectively. CONCLUSION: These results suggested that TUR should be performed as a initial treatment for the patients with grade 3 superficial T.C.C. of the urinary bladder. However, non-papillary tumors should be considered of more intensive treatment like as radical cystectomy, adjuvant chemotherapy or irradiation.

[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.

BRCA1 gene mutation and loss of heterozygosity on chromosome 17q21 in primary prostate cancer.

The tumor suppressor gene BRCA1 on chromosome 17q21 has been characterized and shown to be mutated in patients with familial breast and ovarian cancer. Several studies examined the relatives of women with breast cancer and noted an association with ovarian and prostate cancer. This study investigated 24 human prostate cancer specimens for BRCA1 gene mutations and loss of heterozygosity (LOH) on chromosome 17q21 assessed by the polymerase chain reaction. LOH was identified using 7 highly polymorphic tandem repeat markers on chromosome 17q21, in addition to an analysis of the whole coding region of the BRCA1 gene. Four of the 24 prostate cancer specimens showed LOH at one or more loci, all of which were histologically poorly differentiated (4 of 11) and stage D (4 of 15). One of the 24 cases showed a germ-line mutation of the BRCA1 gene, and a sister of this patient died of ovarian cancer. It appears that the BRCA1 gene is not frequently involved in the development of primary prostate cancer.

Factors influencing morbidity in patients undergoing transurethral resection of the prostate.

OBJECTIVES: Transurethral resection of the prostate (TURP) has become the primary method to relieve bladder outlet obstruction for patients with benign prostatic hyperplasia (BPH). Data from 3861 consecutive patients with BPH who underwent TURP from 1971 to 1996 at our hospital were retrospectively analyzed. METHODS: The patients were classified into two groups comprising 1930 patients who underwent TURP from 1971 to 1985 (early group) and 1931 patients who underwent TURP from 1985 to 1996 (late group). Risk factors associated with blood transfusions and perioperative complications were analyzed in these patients. RESULTS: Mortality, morbidity, and blood transfusions were noted in 5 (0.1 %), 516 (13.4%), and 507 (13.1%) patients, respectively. The blood transfusion and morbidity rates decreased over the 25-year period (P <0.001, chi-square test for trends), which was reflected in a decrease in these rates in the late group (6.1% and 9.5%, respectively) compared with those of the early group (20.2% and 17.2%, respectively). Postoperative bleeding and morbidity were closely related to prostatic gland size and operating time. The most significant differences for the risk of a blood transfusion were related to resection time, the amount of tissue resected, age, and the decade (1970s, 1980s, or 1990s) in which the surgery was performed (P <0.0005), whereas resection time was significantly correlated with morbidity (P <0.0005). As risk factors for each complication, the time of surgical resection, the decade of surgery, and the amount of tissue resected directly correlated with the incidence of extravasation and hemostatic procedures (P < or =0.003), whereas the incidence of postoperative epididymitis positively correlated with a preoperative vasectomy and a closed drainage system (P <0.0005). CONCLUSIONS: Since the 1970s, the rates of blood transfusions and morbidity have decreased for patients undergoing TURP. Advances in techniques, instrumentation, and surgical and perioperative management, including anesthesia, have made TURP a relatively safe procedure, and it remains an effective means for treating patients with BPH.

Expression of Msx genes in regenerating and developing limbs of axolotl.

Msx genes, homeobox-containing genes, have been isolated as homologues of the Drosophila msh gene and are thought to play important roles in the development of chick or mouse limb buds. We isolated two Msx genes, Msx1 and Msx2, from regenerating blastemas of axolotl limbs and examined their expression patterns using Northern blot and whole mount in situ hybridization during regeneration and development. Northern blot analysis revealed that the expression level of both Msx genes increased during limb regeneration. The Msx2 expression level increased in the blastema at the early bud stage, and Msx1 expression level increased at the late bud stage. Whole mount in situ hybridization revealed that Msx2 was expressed in the distal mesenchyme and Msx1 in the entire mesenchyme of the blastema at the late bud stage. In the developing limb bud, Msx1 was expressed in the entire mesenchyme, while Msx2 was expressed in the distal and peripheral mesenchyme. The expression patterns of Msx genes in the blastemas and limb buds of the axolotl were different from those reported for chick or mouse limb buds. These expression patterns of axolotl Msx genes are discussed in relation to the blastema or limb bud morphology and their possible roles in limb patterning.

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.

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.

[Mutation of p53 gene and genomic instability in testicular tumors].

BACKGROUND: During the past decade, studies of human cancer have begun to yield molecular information on the identify of the multiple genetic changes in the development and progression of tumorigenesis. We investigated alterations of p53 and genomic instability in testicular tumors. MATERIALS AND METHODS: Polymerase chain reaction (PCR) single-strand conformation polymorphism was performed for analysis from exons 5 to 8 of p53 gene in 22 cases and PCR-microsatellite instability analysis using 8 microsatellite markers were conducted in 19 cases of testicular tumor. RESULTS: No mutations were noted for exons 5 to 8 of the p53 gene. Differences in unrelated microsatellites for tumor and corresponding normal DNA were detected in 5 of 19 (26.3%) cases examined. Alterations noted in more than 2 microsatellites were observed in 3 of 19 (15.8%) and categorized as replication error (RER) phenotype. Two of 7 (28.6%) seminomatous and 1 of 12 (8.3%) non-seminomatous testicular tumors patients showed RER. Two of 16 (12.5%) stage T1-3N0M0 and 1 of 3 (33.3%) stage T1-3N1-3M0-1 showed RER. CONCLUSIONS: Alterations in microsatellite instability may be involved in the development of testicular tumor.

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.

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.

Receptors for BPH growth factors are located in some neuroendocrine cells.

BACKGROUND: Prostatic neuroendocrine (NE) cells play an important role in the growth and differentiation of the prostate. We are still unable to characterize the exact mechanisms which lead to interactions between the epithelial cell and the NE cell. We offer several interactions generated by the NE cells, and speculate on some actions of selected NE cells. METHODS: We used thin sections of prostatic tissue made from 20 radical prostatectomies. Our team used validated rabbit polyclonal antibodies which were raised against human EGFR and C-erb B-2, using the streptavidin-peroxidase conjugate method. RESULTS: A strong immunoreactivity was noted with both antibodies in the cytosol of some NE cells. These cells had a dendritic appearance, and they were located in the acini and ducts of small-to-moderate-sized prostatic glands. Double immunostaining revealed the colocalization of both antigens with chromogranin A (CgA), a polypeptide that is expressed by NE cells. Of interest was the finding that EGFR and C-erb B-2 were colocalized as well as independently expressed by separate populations of NE cells. CONCLUSIONS: We conclude that NE cells may be regulated by the HER protein family, probably in a ligand-specific fashion. This is a revised report which identifies a pathway regulating NE cells, and their interactions with epithelial cells.

Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry.

Signaling molecules such as Activin, Sonic hedgehog, Nodal, Lefty, and Vg1 have been found to be involved in determination of left-right (L-R) asymmetry in the chick, mouse, or frog. However, a common signaling pathway has not yet been identified in vertebrates. We report that Pitx2, a bicoid-type homeobox gene expressed asymmetrically in the left lateral plate mesoderm, may be involved in determination of L-R asymmetry in both mouse and chick. Since Pitx2 appears to be downstream of lefty-1 in the mouse pathway, we examined whether mouse Lefty proteins could affect the expression of Pitx2 in the chick. Our results indicate that a common pathway from lefty-1 to Pitx2 likely exists for determination of L-R asymmetry in vertebrates.

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.

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.