Bartosz Małkiewicz

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.

The clinical significance of lymphangiogenesis in renal cell carcinoma

Background The formation of lymphatic vessels (lymphangiogenesis) occurs in tumor tissues and is crucial for tumor development and progression in some cancers. Lymphangiogenesis and its clinical effect on renal cell carcinoma have been less thoroughly investigated in comparison with angiogenesis. The aim of this study was to evaluate the role of lymphangiogenesis as a prognostic factor in renal cell carcinoma (RCC). Material/Methods The expression of peritumoral/intratumoral lymphatics was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 133 patients with clear cell carcinoma. Patients were divided into 3 groups depending on postoperative follow-up: I) patients without metastases, II) patients with metastases during follow-up, and III) patients with metastases during the operation. Peritumoral lymphatics (PTL) and intratumoral lymphatics (ITL) were immunostained with a D2-40 antibody. Results The mean number of PTL present in each group was I=14.1, II=10.6, III=12.1. The mean number of ITL present in each group was I=0.7, II=2.3, III=2.3. The 3 groups showed statistically significant differences only in the case of ITL. A mean count of ITL ≥1 is significantly associated with an increased risk of regional lymph node involvement and distant metastasis. Patients with expression ITL >0.2 and PTL ≤15.2 had a significantly shorter cancer-specific survival. Conclusions The number of ITL showed an association with more aggressive cases of RCC and progression of disease. Therefore, the level of expression ITL, together with stage and histological grading, may provide valuable predictive information about the outcome of treatment.

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.

Urological complications after renal transplantation – a single centre experience

Introduction Urological complications after renal transplantation occur in between 2.5% and 30% of all graft recipients. The aim of the study was to present 7 years of experience in urological treatment of patients with a transplanted kidney. We aimed to identify retrospectively late urological complications in renal transplant recipients at a single center and analyze the treatment modalities and their outcome. Material and methods Between January 2008 and December 2014, a total of 58 patients after KTX were treated in the Department of Urology because of post-transplant urological complications that occurred during follow-up at the Transplant Outpatient Department. Retrieved data were analysed in retrospectively. Results In the group of 38 patients with ureteral stenosis (Clavien grade III), 29 patients underwent endoscopy, 8 open surgical procedures and one both endoscopic and open operation. Ten patients were admitted with symptomatic lymphocoele (Clavien III), of which 9 were successfully treated with drainage and one with surgical marsupialization. Because of urolithiasis in the grafted kidney (Clavien grade III), 4 patients were treated with ureterorenoscopic lithotripsy (URSL) and one only with the extracorporeal shock wave lithotripsy (ESWL) procedure. Five urethral strictures plasties and one graftectomy because of purulent pyelonephritis were also conducted. The average age in the group of recipients who experienced urologic complications was similar (46.1 vs. 47.8) to those without complications. There was no vesicoureteral reflux or ureteral necrosis requiring surgical intervention, no graft loss and death related to urological complication and treatment. Conclusions Most complications could be successfully treated with endourological procedures. The kidney function improved in the majority of patients.

Patient comfort during flexible and rigid cystourethroscopy.

Introduction Cystourethroscopy (CS) is an endoscopic method used to visualize the urethra and the bladder. Aim In this study, we prospectively evaluated pain in men undergoing cyclic cystoscopic assessment with rigid and flexible instruments after transurethral resection of bladder tumor (TURB). Material and methods One hundred and twenty male patients who were under surveillance after a TURB procedure due to urothelial cell carcinoma and who had undergone at least one rigid cystourethroscopy in the past were enrolled in the trial. Patients were prospectively randomized to age-matched groups for flexible (group F) or rigid (group R) CS. Patients comfort was evaluated on an 11-grade scale, ranging from 0 (free from pain) to 10 points (unbearable pain). Results The patients described the pain during the previous rigid CS as ranging from 4 to 10 (mean: 6.8) in group F and from 0 to 10 (mean: 5.8) in group R. Group R patients described the pain during the current rigid CS as ranging from 0 to 10 (mean: 5.7). No mean change in the grade was observed between the two pain descriptions (no change 11 patients, weaker pain 25 patients, stronger pain 24 patients, gamma 0.51, p < 0.0001). Group F described the pain as 1 to 5 (mean: 2.1). In the case of flexible CS the pain experience was greatly lowered compared to the previous rigid CS. All flexible CS patients reported lowered pain (by 1 to 9 grades). Patients’ age did not influence the comfort of the flexible CS or the change in pain level. Conclusions Flexible CS is better tolerated than rigid cystoscopy by male patients regardless of patients’ age.

Salvage local therapy for radiation-recurrent prostate cancer – where are we?

Introduction Prostate cancer is the most frequent cancer among males in Europe and a leading cause of cancer deaths, with similar proportion in other developed countries. For more than twenty years, external-beam radiation therapy, alongside with radical prostatectomy, has been used as a primary radical therapeutic approach for localized prostate cancer. Yet, EBRT failures relate to 22–69% following curative radiotherapy (± androgen deprivation therapy). Additionally, a proportion of these men will have a biopsy-proven local recurrence. Material and methods The Medline and Web of Science databases were searched without a time limit during March 2016 using the terms ‘prostate cancer’ in conjunction with ‘radiotherapy’, ‘recurrence’, ‘biochemical’, ‘salvage’, ‘brachytherapy’, ‘prostatectomy’, ‘HIFU’, ‘cryotherapy’ and ‘focal’. The search was limited to the English, Polish, German and Spanish literature. Results Currently, salvage treatment after failed radiotherapy includes radical prostatectomy, brachytherapy and ablative whole-gland therapies, such as cryotherapy and high intensity focused ultrasound. New approaches, so called focal salvage therapy, involve ablation of only the zone of recurrence in order to decrease tissue injury and therefore to diminish morbidity. Conclusions At present no authoritative recommendations can be concluded because of the absence of randomized data with standardized definitions and protocols. Nevertheless, we believe that local salvage treatment should be at least considered in patients after biochemical relapse following radiotherapy.

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.

Laparoscopic radical nephrectomy in extremely obese patients.

Laparoscopic radical nephrectomy has been widely accepted as the preferred management of low stage renal masses. Endoscopic management is advantageous for its reduction in perioperative and postoperative complications. In the mid-1990s, morbid obesity was considered a relative contraindication to laparoscopic technique. The authors present two cases of laparoscopic radical nephrectomy due to renal tumors in extremely obese patients. The aim of this study is not only to present the operative technique but also to show that the laparoscopic procedure is safe and effective in morbidly obese patients.