Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer.

BACKGROUND/AIMS: This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance. METHODS: To determine the relationship between the gene expression pattern, global methylation and promoter methylation status, we performed real-time PCR to quantify the mRNA of selected genes in 50 samples of bladder cancer and adjacent non-cancerous tissue. The methylation status was analyzed by methylation-specific polymerase chain reaction (MSP) or digestion of genomic DNA with a methylation-sensitive restriction enzyme and PCR with gene-specific primers (MSRE-PCR). The global DNA methylation level was measured using the antibody-based 5-mC detection method. RESULTS: The relative levels of mRNA for MBD4, MLH3, and MLH1 were decreased in 28% (14/50), 34% (17/50) and 36% (18/50) of tumor samples, respectively. The MBD4 mRNA expression was decreased in 46% of non-muscle invasive tumors (Ta/T1) compared with 11% found in muscle invasive tumors (T2-T4) (P<0.003). Analysis of mRNA expression for TDG did not show any significant differences between Ta/T1 and T2-T4 tumors. The frequency of increased DNMT1 mRNA expression was higher in T2-T4 (52%) comparing to Ta/T1 (16%). The overall methylation rates in tumor tissue were 18% for MBD4, 25% for MLH1 and there was no evidence of MLH3 promoter methylation. High grade tumors had significantly lower levels of global DNA methylation (P=0.04). There was a significant association between shorter survival and increased expression of DNMT1 mRNA (P=0.002), decreased expression of MLH1 mRNA (P=0.032) and the presence of MLH1 promoter methylation (P=0.006). CONCLUSION: This study highlights the importance of DNA repair pathways and provides the first evidence of the role of MBD4 and MLH3 in bladder cancer. In addition, our findings suggest that DNMT1 mRNA and MLH1 mRNA expression, as well as the status of MLH1 promoter methylation, are attractive prognostic markers in this pathology.

Radiofrequency ablation of small symptomatic angiomyolipomas of the kidney: Report of two cases.

BACKGROUND: The development of more sensitive imaging techniques caused an increase in the number of diagnosed small renal tumors. The small size of the lesions allows for their treatment with minimally invasive nephron-sparing methods. Approximately 2-3% of these lesions are proved to be angiomyolipomas (AML). AML is a rare benign tumor of the kidney, sometimes causing pain and hematuria. The most commonly required approach is observation but in case of recurrent symptoms or larger tumors which may cause bleeding, a more active treatment is needed. This paper demonstrated the evolution of our attitude leading to utilization of radiofrequency ablation (RFA) as a minimally invasive option in the management of small symptomatic AMLs of the kidneys. MATERIAL/METHODS: We presented clinical data of two cases of symptomatic AML tumors in the kidney, treated with RFA. The tumors were diagnosed on the basis of a contrast-enhanced CT (computed tomography) scan. The probe was inserted into the lesion percutaneously under USG (ultrasonography) guidance. RESULTS: RFA proved to be an effective and safe method of treatment of renal AMLs. A follow-up carried out after 1.5 and 3 years, basing on contrast-enhanced CT tests, confirmed a complete ablation of the AML and decreased tumor size. CONCLUSIONS: Promising results of RFA in the management of AML may encourage urologists and radiologists to use this minimally invasive technology and to qualify patients for this treatment more often and thus to prevent potential complications in the future.

There is no place for targeted therapy neoadjuvant treatment in Polish Health System - An analysis of radical nephrectomies in patients with large kidney tumors.

INTRODUCTION: Despite the introduction of better diagnostic tools, very large kidney tumors are still not so rare in our country. The paper presents our experience in the treatment of 12 patients with kidney tumors larger than 14 cm in size. MATERIAL AND METHODS: Between spring 2009 and autumn 2011, radical nephrectomies were performed in 12 patients due to a large kidney tumor (larger than 14 cm in size). Symptoms (hematuria, weight loss, anemia, etc.) were not present in all the patients, but the kidney tumor was confirmed by imaging studies (ultrasound, CT, MRI) in all of them. RESULTS: Full recovery was observed with no severe complications in all of the patients treated with radical nephrectomy. Pathological staging was correctly established by imaging studies in all of them. After a few months, five of patients (41.6%) required systemic therapy due to lymph node involvement. CONCLUSIONS: Patients with large kidney tumors should be treated in selected medical centers that have experience in the treatment of such cases. Radical nephrectomy has to be the method of choice in the treatment of patients with this kind of tumor and its diameter should not disqualify from surgical treatment, which is still the only chance for the patients to be cured, as no adjuvant chemotherapy treatment has proved to be significantly effective.

Normal variants in patients consulted in the Dermatology Clinic for lesions of the male external genitalia.

INTRODUCTION: So far there have been no papers analyzing the incidence of 'non-pathological' lesions or normal variants on the male external genitalia. Subsequently, the number of patients consulted due to the presence of such lesions remains unknown. The aim of the study was to estimate the incidence of normal variants in patients who were consulted due to lesions on the skin or mucosa of the male external genitalia. MATERIAL AND METHODS: The study group consisted of 400 males, aged 3-91, who were consulted due to lesions on the genitalia in the Department of Dermatology, Venereology and Allergology of the Medical University of Gdansk. RESULTS: The most common lesions were hyperpigmentation of the median raphe of the penis and scrotum (85.6%), pearly penile papules (24%), and prominent veins (24%). Sebaceous hyperplasia or ectopic sebaceous glands were revealed in 9% of patients, respectively. Melanocytic nevi were diagnosed with similar frequency (9.5%), whereas skin tags more rarely (7%). Other 'non-pathological' lesions were diagnosed in a considerably lower number of patients. In 32 patients (8% of all patients) the reason of admission to the Clinic was just the presence of some 'non-pathological' lesions. Pearly penile papules were found to be the most common condition, occurring in 78.1% patients. CONCLUSIONS: Normal variants represent a substantial percentage of generally asymptomatic lesions and the only indication for their removal is cosmetic discomfort or venerophobia.

Operative shortening of the sling as a second-line treatment after TVT failure.

INTRODUCTION: Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during physical exertion, sneezing, coughing, laughing, or other activities that put pressure on the bladder. In some cases, recurrent or persistent SUI after sling operations may be caused by too loose placement of the sling. In the current study, we describe our method of shortening of the sling as a second-line treatment of tension-free vaginal tape (TVT) failure. MATERIALS AND METHODS: Four women, aged 46-61, after initial TVT operation were treated for persistent SUI. The severity of SUI was estimated by: physical examinations, cough tests, 24-h pad tests, and King's Health Questionnaire. The shortening procedure, based on excising the fragment of tape and suturing it back, was performed in all patients. RESULTS: All cases achieved a good result, which was defined as restoration of full continence. No complications occurred. The 12-month follow-up showed no side-effects. The postoperative control tests: the cough and 24-h pad tests were negative in all women. The general health perceptions increased after the shortening procedure by a mean value 44.25%. The incontinence impact decreased by a mean value 44.6%. In all patients, role and physical limitations significantly decreased (by 88.5% and 80.5%, respectively). The negative emotions connected with SUI significantly decreased after the second procedure. CONCLUSIONS: The operative shortening of the implanted sling is a simple, cheap, and effective method of second-line treatment in cases of TVT failure and may be offered to the majority of patients with insufficient urethral support after the first procedure.

Acute urinary retention in a patient with extended cystitis glandularis.

Cystitis glandularis (CG) is defined as glandular metaplasia of bladder urothelium. In most cases the course of CG is asymptomatic. However, some patients complain of hematuria and lower urinary tract symptoms (LUTS) of varying degrees. We present a case of 45-year-old man with an extensive CG causing acute urinary retention. Although it was initially treated as an infection, prompt ultrasound and cystoscopy helped to establish the diagnosis. Transurethral resection of the cyst with biopsy of the bladder mucosa was then performed. Immediately after surgery the patient noticed significant improvement in urine passing. During the 2-month follow-up there was no relapse.

Impact of radiofrequency ablation on PBMC subpopulation in patients with renal cell carcinoma.

PURPOSE: With the development of diagnostic techniques, renal cell carcinoma (RCC) is currently diagnosed in earlier stages, allowing the introduction of less invasive techniques in its management. One of the most promising new treatment methods is based on the utilization of high temperature created by radiofrequency current circulating around the needle probe introduced into the tumor. Besides the direct destruction of the cancer tissue, the treatment may induce immunologic reaction to tumor antigens released from destroyed tumor cell. This paper describes changes observed in the peripheral blood lymphocyte population after radiofrequency ablation (RFA) of RCC. METHODS: Blood was tested before, and 2, 4, and 6 weeks after the RFA in 6 patients with RCC for the proportions and numbers of CD3(+), CD3(+)HLA-DR(+), CD3(+)CD4(+), CD3(+)CD8(+), and CD56(+)CD16(+) cells. The blood was stained with fluorochrome-conjugated monoclonal antibodies and percentages of cells expressing various markers were determined by flow cytometry. RESULTS: In all patients, the changes were most pronounced 2 weeks after the procedure. The proportion of CD4(+) and CD8(+) lymphocytes were changed. In 1 patient, an increase in both CD4(+) and CD8(+) cells was observed. In 5 out of 6 patients, the proportion of activated (DR(+)) cells was increased over the whole follow-up period with the highest values in the second week after RFA. The percentage of the CD56(+)CD16(+) was decreased in most of the patients. CONCLUSIONS: Our study confirms that in the majority of patients, RFA of the renal tumors causes significant changes in the proportion of the peripheral immune cells. We suggest that the results presented in this article shows the necessity for further studies.