High frequency of deletion on chromosome 9p21 may harbor several tumor-suppressor genes in human prostate cancer.

Chromosome 9p has been reported to be a critical region of loss in various cancers. Our present study was designed to determine the frequency of deletions at different loci of chromosome 9p in microdissected samples of normal prostatic epithelium and carcinoma from the same patients. For this purpose, DNA was extracted from the microdissected sections of normal and tumor cells of 40 prostate specimens, amplified by PCR and analyzed for loss of heterozygosity (LOH) on chromosome 9p using 15 microsatellite markers. Only 6 of 15 microsatellite markers exhibited LOH in prostate cancer specimens (D9S162, D9S1748, D9S171, D9S270, D9S273 and D9S153). LOH on chromosome 9p was identified in 29 of 40 cases (72.5%) with at least 1 marker. The main deletion was found on 9p21, at loci D9S1748 (50%), D9S171 (51.4%) and D9S270 (21.8%). There was also a deletion on 9p22 at locus D9S162 (8.3%), on 9p13 at locus D9S273 (13.8%) and on 9p11 at locus D9S153 (7.7%). LOH data were correlated with stage of prostate cancer and revealed a high frequency of LOH at 3 or more loci in samples with stage T(3)N(0)M(0) (46%) compared with stage T(2)N(0)M(0) (15%), which suggests a higher incidence of LOH in the advanced stage of prostate cancer. One of the candidate target tumor-suppressor genes, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in tumor cell lines. Expression of P16 protein was either absent or very low in prostate cancer samples, suggesting that loss of the p16 gene may be involved in prostatic carcinogenesis.

Loss of two new loci on chromosome 8 (8p23 and 8q12-13) in human prostate cancer.

Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mechanism of gene alterations in prostatic carcinogenesis. Loss of sequences on the short arm of chromosome 8 (8p) has been reported in human cancers, especially of 8p22 and 8p12-21 in prostate cancer. By using PCR analysis of polymorphic microsatellite repeat markers at four 8p loci and three 8q loci in 60 tumors, we observed deletion of sequences at two other deletion domains (8p23, and 8q12-13). There was loss in 51 of 60 cases (85%) with at least one marker. Four distinct regions of loss detected were: i) at 8p23, at locus D8S262; ii) at 8p22, on locus D8S259; iii) at 8p12, on loci D8S255 and D8S285; iv) at 8q12-13, on loci between D8S260 and D8S528. We found that 29% of the tumors showed LOH at 8p23; 19% LOH on 8p22; 54% had LOH at 8p12; and 48% had LOH at 8q12-13. There was higher frequency of LOH at 3 or more loci in samples of T3 stage (62%) as compared to T2 stage (13.3%) which suggests higher incidence of LOH in advanced stage of prostate cancer. We report deletion of two novel loci at 8p23 and 8q12-13, these regions may contain putative tumor suppressor genes in prostate cancer.

Fifty years of antireflux ureterovesicoplasty.

In spite of the impressive progress in medical science, surgery remains an empirical skill. Surgery of the ureterovesical junction is a permanent challenge for all generations of urologists. Half a century of intensive development of modern surgery evidences the efforts to reestablish function by a perfect copy of natural anatomy.

Uroflow via stenotic urethra.

A DANTEC 2100 mictometer type 21C10 with uroflow transducer type 21KO2 was used for investigation of 50 men with urethral strictures (mean age 59 +/- 14 years). The patients underwent a total of 334 clinical evaluations of replicate voiding (minimum 4, maximum 16) before and after successful urethral dilatation on an outpatient basis. Using t-paired comparison test, significant increase in maximum urinary flow rate (P less than 0.01) after the treatment procedure was evidenced in each of the patients. The variability of other urinary flow parameters suggested a lower significance in evaluation of urine stream quality. The McNemar test showed a significant shift from one to another zone of classification suggested by Drach et al. (P less than 0.01), i.e. 64% of patients reached normal or overlap zone in the first spontaneous voiding after urethral dilatation. Furthermore, no significant difference could be established with one-way ANOVA between urodynamic variables of mean values of repetitive voidings in cases of urethral stenosis of different aetiology either before or after urethral dilatation (P greater than 0.05), suggesting that urethral stenoses of different aetiology are characterized by similar urodynamic features. A highly significant linear correlation was found between the maximum flow rate and the voided volume only after urethral dilatation (r = 0.522, P less than 0.01), while correlation with urethral sound sizes could not be established (r = 0.207, P greater than 0.5). We conclude that uroflowmetry provides reliable information on the patient's ability to void. The use of maximum flow rate may predict the time at which urethral dilatation becomes necessary and provides objective evidence of the efficacy of treatment.

Balkan endemic nephropathy and papillary transitional cell tumors of the renal pelvis and ureters.

Papillary transitional cell tumors of the renal pelvis and ureters occur more frequently in the Balkan countries than in other areas in the world. The populations involved are the same as those who are at risk to develop Balkan endemic nephropathy (BEN). Seventy-seven patients were treated in the Urology Clinic for papillary cell tumors of the renal pelvis and ureters (UTT) from 1986 to 1988. Forty-four of the patients were from areas where BEN is endemic. The at-risk population is estimated to be less than 2% of the control population. Eleven of the 77 were on hemodialysis when UTT were detected, and all but one of those were from BEN areas. This finding emphasizes the need for continual monitoring of end-stage renal disease patients for evidence of these tumors. Comparing the frequency of the tumors from our study (1986 to 1988) with that of early studies indicates that the risk of developing the tumors remains very high in the BEN areas. We conclude that the causative agent(s) is still prevalent in the involved areas.

Non-antireflux versus antireflux ureteroneocystostomy in adults.

A retrospective analysis of ureteric reimplantation in adults showed that a high proportion (71%) had been treated by non-antireflux procedures. Analysis of the ureteroneocystostomy success rate in aetiological groups where either antireflux or non-antireflux techniques were used indicated the superiority of antireflux surgery in the prevention of reflux. The risk of stenosis at the site of anastomosis was equal in both groups. No significant difference in the preservation of renal function was detected in the 2 groups. It was concluded that antireflux procedures offered no advantage over non-antireflux ureteric reimplantation in adults.