Krzysztof Bar

BRCA1 mutations and prostate cancer in Poland

Evidence to date that BRCA1 mutation carriers are at an increased risk of prostate cancer is mixed – both positive and negative studies have been published. To establish whether or not inherited variation in BRCA1 influences prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and 4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.45% of the cases and 0.48% of the controls (odds ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC mutation is the most common of the three founder mutations. It was detected only in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9–27.9; P=0.1). The C61G mutation was also found in excess in cases (0.17%) compared with controls (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5–12.7; P=0.5). Eight men with prostate cancer carried a mutation. Only one of these carried the 5382insC mutation, compared with 17 of 22 individuals with mutations in the control population (P=0.003). These data suggest that the 5382insC mutation is unlikely to be pathogenic for prostate cancer in the Polish population. The presence of one of the other alleles was associated with an increased risk for prostate cancer (odds ratio=3.6; 95% confidence interval: 1.1–11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9–51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland

The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20‐fold). The geographical and ethnic extent of this recurrent allele has not yet been determined.

A common nonsense mutation of the BLM gene and prostate cancer risk and survival

BACKGROUND Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet. METHODS To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls. RESULTS Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases. CONCLUSIONS BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland.

The presence of prostate cancer at biopsy is predicted by a number of genetic variants

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low‐risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.

The value of EORTC risk tables in evaluating recurrent non–muscle–invasive bladder cancer in everyday practice

Introduction Due to the risk of recurrence and progression, patients with non–muscle–invasive bladder cancer have to be under observation. The aim of this study is the evaluation of early recurrence at the first control cystoscopy, as a prognostic factor for recurrence and progression based on EORTC risk tables. Material and methods This study analyzed 243 patients with non–muscle–invasive bladder cancer, with an average observation time of 46 months. Recurrence was observed in case of 99 patients. Among these patients, we selected 79 who had the first cystoscopy 3 months after the transurethral electroresection of the bladder tumor. Subsequently, 45 patients with early recurrence at the first control cystoscopy were compared with 34 patients whose cancer recurred at later control cystoscopies. The patients were compared with respect to the number of points assigned by EORTC tables. Results Those patients who had an early recurrence had a significantly higher score in the EORTC table in the progression scale (p = 0.017) but not in the recurrence scale (p = 0.11), as compared with patients who had a late recurrence. Conclusions Early recurrence that occurs within 3 months after TURBT indicates a higher risk of progression, as compared with a late recurrence. Patients who had an early recurrence had a significantly higher EORTC risk score for progression. Their EORTC risk score for recurrence was also higher, but the difference was not statistically significant. Every patient with an early recurrence has a worse prognosis and a higher risk of progression.

Partial cystectomy in a 76 year old patient suffering from small cell carcinoma of the urinary bladder

Small cell carcinomas of the urinary bladder originating from the neuroendocrine cells are extremely rare. We present a case of a 76–year–old patient with small cell carcinoma of the urinary bladder. The patient had hematuria and cystoscopy revealed a tumor located in a urinary bladder diverticulum. Partial resection of the bladder wall with diverticulectomy was performed. Microscopic examination established the diagnosis of neuroendocrine carcinoma, which was confirmed by immunohistochemistry. Three–month follow–up showed no recurrent disease. Patient refused further chemotherapy and radiotherapy.

Minimally invasive treatment of prostatic abscess - percutaneous transvesical drainage.

We currently treat prostatic abscess with minimally invasive methods, most frequently with transurethral (TURP) or transrectal drainage under visual control with TRUS. We present an example of prostatic abscess drainage by percutaneous and transvesical means under the control of ultrasonography (USG). With a 9F single-stage drainage kit, the prostatic abscess was punctured through the abdominal skin and bladder in one step. We found this method to be straightforward for urology and safe for the patient.

The variant allele of the rs188140481 polymorphism confers a moderate increase in the risk of prostate cancer in Polish men.

A number of single nucleotide polymorphisms (SNPs) in the human genome have been associated with increased risk of prostate cancer. Recently, a single SNP in the region of chromosome 8q24 (rs188140481) has been associated with a three-fold increased risk of prostate cancer in Europe and North America. To establish whether rs188140481 is associated with the risk of prostate cancer in Poland, we genotyped 3467 men with prostate cancer and 1958 controls. The A allele of rs188140481 was detected in 44 of 3467 (1.3%) men with prostate cancer and in seven of 1958 (0.4%) controls (odds ratio=3.6; 95% confidence interval 1.6–7.9; P=0.0006). The allele was present in eight of 390 (2.1%) men with familial prostate cancer (odds ratio=5.8; 95% confidence interval 2.1–16.2; P=0.001). A positive family history of cancers at sites other than the prostate was observed in 27% of men who carried the rs188140481 risk allele and in 44% of noncarriers (P=0.04). No cancer at a site other than the prostate was more common in first-degree or second-degree relatives of carriers of the rs188140481 risk allele than relatives of noncarriers. The rs188140481 polymorphism in the 8q24 region confers a moderate increase in the risk of prostate cancer in Polish men. The SNP does not appear to be associated with susceptibility to cancers of other types.

An uncommon case of inflammatory infiltration of the urinary bladder in the long–term process of the purulent inflammation of the cervix and vaginal fornix, complicated with vesicovaginal fistula of unknown etiology

We shall discuss the case of a female patient, aged 64 years, who was suffering from long–term purulent inflammation of the vaginal fornix that later involved the vaginal stump. This inflammatory process spread to the bladder trigone and resulted in vesicovaginal fistula (VVF) formation together with a bilateral hydronephrosis that required the placement of a temporary percutaneous nephrostomy. A non–cicatrized inflammatory reaction occurred at the right–sided insertion of the nephrostomy, which has yet to be successfully treated despite intensive dermatological and surgical approaches that included skin grafting. In the course of five–year treatment we observed a gradual regression of the inflammatory infiltration of both the trigone of the bladder and the vagina as well as a gradual closing of the VVF. The extremely long–lasting and uncommon local inflammatory reactions in the vagina, bladder, and dermal layers mandated the application of conservative treatment. The possibility of difficulties and defective healing of tissues that could result from surgical correction of the VVF are discouraging for both the patient and medical staff.

A rare case of left kidney and ureter duplication with ectopic orifice in vagina. Diagnosis, complications, treatment

The objective of the study was to present a rare case of a double pyelo-calyceal system and duplicated ureter leaving the left kidney diagnosed in a female patient. The ureter was descending from the upper segment of the left kidney with an ectopic orifice into the vagina. The condition resulted in enuresis ureterica. We present diagnostic and therapeutic processes that often pose difficulties for many specialists, including urologists, gynecologists, surgeons, radiologists and pediatricians. fig. 1. Intravenous pyelography. No leakage of contrasted urine in the upper segment of left kidney.