Shin Egawa

Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan

Objectives To assess the time trends, morbidity and mortality of contemporary anatomical radical retropubic prostatectomy (RRP) in a multi‐institutional study in Japan, where RRP has become more popular in the last decade.

p53 Mutations and Prognosis in Bladder Tumors

The incidence of loss of heterozygosity on chromosome 17p and p53 gene mutations was assessed in 43 bladder tumor patients. Histological findings, cigarette smoking and prognosis were examined for possible correlation with the presence or absence of loss of heterozygosity on 17p and p53 mutations. Of 20 informative cases 10 (50.0%) showed loss of heterozygosity of 17p13, including 9 (90.0%) with disease beyond stage pT2. The p53 mutations were detected in 20 of 43 patients (46.5%), including 9 (95.0%) with disease beyond grade 2 and 17 (85.0%) with cancer beyond stage pT2. The incidence of p53 gene mutations was not significantly influenced by habitual smoking but G:C to T:A substitutions, often observed in lung cancers, were detected only in mutations from smokers (5 of 10 or 50%, p < 0.05). Groups with and without loss of heterozygosity showed essentially the same results, while significant differences were found for groups with grades 1 and 2 to 3 (p < 0.05) cancer, stages pT1 and pT2 to 4 (p < 0.01) disease, and with and without p53 gene mutations (p < 0.01, Cox-Mantel test). Genetic alternation in chromosome 17p and p53 mutations would, thus, appear to occur more frequently in high grade and invasive bladder tumors. Cigarette smoking may possibly be a determining factor of mutations of the p53 gene in bladder tumors. Our results indicate that an unfavorable prognostic factor may possibly be linked not only to histopathological findings but the presence of a p53 mutation in bladder tumors as well. Accordingly, mutations of the p53 gene may be deeply involved in late events of tumorigenesis and possibly useful as ideal molecular markers for prognosis in bladder tumors.

Anterior distribution of stage T1c nonpalpable tumors in radical prostatectomy specimens

OBJECTIVES To determine the anatomic patterns of tumor distribution in radical prostatectomy specimens from nonpalpable prostate cancer. METHODS Tumor maps directly traced from histologic slides of 62 radical prostatectomy specimens were superimposed by a computer-assisted imaging technique to create an idealized prostate gland at three levels: apex, mid-prostate, and base. To investigate specific patterns of tumor distribution, the sites of tumor in each quadrant were compared according to risk group stratification. The tumor extent was compared with the patterns of positivity in routine sextant biopsies. RESULTS Among all patients, the tumor frequency was 85.5% in the mid-gland, 82.3% in the apex, and 48.4% in the base. Analysis by quadrant showed that tumors were significantly denser in the apex to mid-prostate. The primary extent of these tumors appeared to lie predominantly in the anterior half of the gland. Biopsy yields at the apex and mid-prostate appeared low compared with the frequency of cancers at these levels. No patterns specific to the different risk groups were found, but no tumors within the anterior base were found in the low-risk group. CONCLUSIONS The primary extent of nonpalpable tumors appeared to lie predominantly in the anterior half of the gland at the apex to mid-prostate levels. Additional biopsy cores taken from more anterior regions of the gland may enhance the detection of nonpalpable cancers further.

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.

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.

Does Transurethral Resection of the Prostate Pose a Risk to Life? 22-Year Outcome

The clinical outcomes of 717 patients who underwent transurethral resection for benign prostatic hyperplasia between 1971 and 1981, and of 48 who underwent open prostatectomy during the same period were evaluated. All living patients could be followed for a minimum of 12 years postoperatively. The cumulative percentage of patients undergoing a secondary operation was substantially greater after transurethral resection of the prostate than after open prostatectomy. The volume of resected tissue, operating time, requirement for blood transfusion and hyponatremia during or after the procedure did not affect long-term outcome of patients in the transurethral resection group. Abnormal preoperative electrocardiography and azotemia appeared to be associated with increased risk of postoperative mortality after controlling for other variables (p < 0.05). Actuarial survival rates did not differ substantially for patients who underwent transurethral resection and open prostatectomy, and exceeded the expected survival rates in the general male population in the same age group in Japan. Both procedures are safe for the symptomatic relief of urinary obstruction due to benign prostatic hyperplasia. Prostatectomy does not jeopardize long-term survival of the patients.

Use of pretreatment prostate specific antigen doubling time to predict outcome after radical prostatectomy.

The objective of this study was to better understand the implications of the rate of prostate-specific antigen (PSA) changes in prostate carcinoma. We retrospectively calculated PSA doubling times prior to surgery in 62 patients with prostate carcinoma. The calculated values were compared with final pathologic findings and with rates of PSA failure after surgery. PSA values increased during the period of observation in 82.3% of the patients, whereas 17.7% had levels that remained stable. The median calculated PSA doubling time in those with increasing levels was 25.8 months, with doubling times ≤24 months observed in 37.1% of the patients. Stage pT3 disease was more common in patients with PSA doubling times of ≤36 months than in those with doubling times >36 months (P=0.02). Biochemical failure was more common in patients with rapid PSA doubling times (P<0.01). The calculated PSA doubling time prior to radical surgery is significantly associated with the final pathologic findings. Early PSA failure is more common in patients with rapid PSA doubling times prior to radical surgery.

Parathyroid Hormone-Related Protein Is an Independent Prognostic Factor for Renal Cell Carcinoma

Parathyroid hormone‐related protein (PTHrP) has been shown to be the principal cause of humoral hypercalcemia associated with renal cell carcinoma (RCC). Recent studies have demonstrated that the amino‐terminal region of PTHrP has growth factor‐like activities, suggesting it may play a role in the development of RCC. In this study, expression of the carboxy‐terminal region of PTHrP was assessed immunohistochemically and its significance in predicting the prognosis of RCC was studied.

Infrequent involvement of p53 mutations and loss of heterozygosity of 17p in the tumorigenesis of renal cell carcinoma

Restriction fragment length polymorphism (RFLP) analysis and the polymerase chain reaction of the single-strand conformation polymorphism (PCR-SSCP) method were conducted to assess the loss of heterozygosity of chromosome 17p and mutations of the p53 gene in 30 surgical specimens of human renal cell carcinoma. Six of 29 tumors (20.6%) showed loss of heterozygosity on chromosome 17p in RFLP analysis, and in none of 21 tumors could a mutation be found on exons 5 to 8 of the p53 gene in PCR-SSCP analysis. We conclude that the p53 gene mutation does not play a role in the development of the majority of cases of renal cell carcinoma and that there may be another tumor suppressor gene on 17p.

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.