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Background. Prostate cancer increasingly is becoming a medical problem in Japan. To maximize the chance for cure, extensive effort is being made to detect prostate cancer while confined to the gland.Methods. Determination was made of serum prostate specific antigen (PSA) in the early detection of prostate cancer in an Asian male population aged 55 years or older. Recommendation for biopsy was based solely on this parameter when its value exceeded 2.0 ng/ml in IMx immunoenzymetric assay.Results. Of 1189 men, 150 (12.6%) had elevated values. The proportion of males with serum PSA greater than 4.0 ng/ml was only 3.4%. Of the 99 males who underwent ultrasound-guided biopsies, 16 cancers were detected, a cancer detection rate of 1.3%. Most of these (81.3%) were clinically localized cancers. Seven patients with cancer had serum PSA levels below 4.0 ng/ml including 5 less than 3.0 ng/ml. These tumors would have been overlooked if the conventional cutoff levels of 4.0 ng/ml had been applied. Radical prostatectomy was conducted on 13 patients. All had histologic features of clinically significant cancer and 69.2% were pathologically confined within the gland.Conclusions. Elderly Asian males appear to have lower serum PSA than their Western counterparts. The optimal cutoff of serum PSA for early detection should be examined further in Asian male populations. Differences in the incidence of prostate cancer between ethnic groups may have been overestimated in previous studies owing in part to unawareness by the physician and general public. Though the frequent use of more sophisticated diagnostic modalities will likely disclose greater numbers of prostate cancers in Japan, whether early detection reduces mortality by minimizing risk of death from cancer remains a point to be determined. Cancer 1995; 76:463-72.

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. Int. J. Cancer (Pred. Oncol.) 84:19–23, 1999. © 1999 Wiley-Liss, Inc.

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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°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.

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.

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 a further 20 (36.4%) and the transition zone biopy 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.

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 significant 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.

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 ≥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.

Preoperative parameters were assessed for their usefulness in predicting tumor volume in 26 cases of nonpalpable prostate cancer. The number of positive biopsy cores was found to be the parameter which predicted most accurately tumor volume in surgical specimens. All 14 patients with multiple positive cores had an index tumor of 0.5 cm3or more in radical prostatectomy specimens. Only six tumors with a single positive core were substantial. Three of the patients showed a serum level of prostate specific antigen (PSA) of 4.0 ng/ml or more. The pathological stage and prostatectomy Gleason sum could not be predicted accurately by this variable (P< 0.05). To predict index tumor volumes of 1.0 cm3or greater, stepwise logistic regression analysis was conducted, and on the basis of the results it was possible to single out multiple positive biopsies as the only significant variable. The number of positive biopsies appeared reliable for predicting tumor volume of surgical specimens in cases of nonpalpable disease. The presence of significant tumors despite “normal” levels of PSA warrants further investigation of variables that can predict such prostate cancers. An adequate model for predicting significant tumors in oriental male populations should be established using samples of larger size.

We evaluated the usefulness and safety of a bladder neck support prosthesis in patients with stress or mixed incontinence.

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.

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.

In infertile men, clinical varicoceles most often occur bilaterally. In our experience with these patients, both testicles are smaller than normal. We find more than 25% to 35% immature and tapered sperm in in the ejaculum of these men, and the motility of the sperm is usually low. We have found serotonin in the plasma of the varicoceles, and believe this biogenic amine is responsible for the poor sperm motility. We now agree that a subset of neuroendocrine cells in the prostate secrete serotonin. Bilateral varicocele surgery can improve the patient's fertility potential, and we advocate surgical treatment.

Procedures of Japanese urologists of interventional therapy for benign prostatic hyperplasia (BPH) should be defined for resource economy and policy establishment.

We report a case of malignant pheochromocytoma associated with prostaglandin E producing hypercalcemia.

A new intraoperative renal radiography technique using Polaroid film is presented. The quality of the Polaroid radiograph is satisfactory enough to visualize radiopaque calculi and provides good information on the localization of intrarenal calculi in a short time. The time required for photographic development is 15 seconds and a dark room is not necessary.

Polaroid radiography is a useful and convenient method for prompt intraoperative renal radio-graphs of excellent quality during nephrolithotomy. We describe a new self-developing film cassette.