Ken Koshiba

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.

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.

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.

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.

Bladder neck support prosthesis : A nonoperative treatment for stress or mixed urinary incontinence

PURPOSE We evaluated the usefulness and safety of a bladder neck support prosthesis in patients with stress or mixed incontinence. MATERIALS AND METHODS A total of 57 women with stress and 20 with mixed incontinence completed a 12-week prospective clinical trial of a bladder neck support prosthesis. While indexes of incontinence episodes, leakage amounts and urgency along with a bothersome index were subjectively evaluated, a 60-minute pad test and urinary flow parameters were objectively evaluated. Three patients scheduled to undergo surgery for stress incontinence voluntarily used the device, and provided urodynamic data and cystourethrograms. Two prongs at 1 end of the ring, a type of elastic vaginal pessary, elevate the bladder neck against the pubic bone and facilitate pressure transmission around the bladder neck, resulting in urinary continence. RESULTS Four subjective indexes significantly improved. There was no urinary flow obstruction. Urine loss decreased from 20.6 to 4.8 gm. per hour (p < 0.001) on the 60-minute pad test. Of the patients 22 (29%) reported complete continence and 39 (51%) had decreased severity of incontinence by more than 50%. Minor adverse effects occurred in 26% of the patients. Taking subjective evaluation, changes in objective parameters and adverse effects into consideration, 62 patients (81%) had some or maximum benefit according to the global usefulness rating. CONCLUSIONS The bladder neck support prosthesis is safe, well tolerated and clinically effective for the treatment of stress or mixed incontinence.

Malignant Fibrous Histiocytoma of the Bladder with Focal Rhabdoid Tumor Differentiation

A case of primary malignant fibrous histiocytoma of the bladder is presented. This tumor involving the bladder is rare and the unusual histological features in the present case caused significant delay in accurate diagnosis. Since early diagnosis and aggressive surgical resection are essential to the effective treatment of this neoplasm, physicians should continually bear in mind the possibility of this malignant tumor whenever the pathological diagnosis is inconclusive.

HIGH INTENSITY FOCUSED ULTRASOUND FOR BENIGN PROSTATIC HYPERPLASIA

Background:

MICROSATELLITE INSTABILITY IN TRANSITIONAL CELL CARCINOMA OF THE URINARY TRACT AND ITS RELATIONSHIP TO CLINICOPATHOLOGICAL VARIABLES AND SMOKING

To determine whether microsatellite instability is involved in the development of transitional cell carcinoma (TCC) of the urinary tract, a microsatellite instability assay was carried out using PCR with 9 microsatellite loci. Thirty‐eight TCC samples (30 patients with bladder cancer, 5 with renal pelvic tumors and 3 with ureteral tumors) and 1 lymph node with metastasis were examined. Microsatellite instability was found in 8 of 38 tumors examined, and 3 showed alterations in more than 2 microsatellite loci. All 8 tumors were beyond grade 2 and stage pT2 advanced tumors. Stages pT1‐2 and pT3‐4 patients differed significantly. Microsatellite instability was greater in smokers than non‐smokers, but the differences were not significant. Microsatellite instability in TCC of the urinary tract is rare in superficial tumors but more common in invasive tumors. Microsatellite alterations would thus appear to occur, and possibly be importantly involved, in the tumorigenesis of urinary tract TCC.