Gergely Bánfi

Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype.

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.

Treatment and outcome of vaseline-induced sclerosing lipogranuloma of the penis.

OBJECTIVES To study the treatment and short-term outcome of 16 consecutive cases of sclerosing lipogranuloma of penis developing after Vaseline inoculation for penile augmentation. METHODS After Vaseline inoculation, patient pain was related mainly to erection and severe phimosis. At surgical reconstruction complete and radical excision of the involved penile skin was performed, followed by skin substitution from the existing, saved coat of the penis. In most cases the stored, uninvolved inner preputial skin was used; less frequently scrotal flaps and in the least-favorable cases penis embedment in the scrotum was applied for coverage of the penis. RESULTS All 16 patients were cured, no matter how long after self-injection vaselinoma developed or which kind of surgery was performed. Histopathologic evaluation revealed different findings according to the time elapsed after Vaseline injection. CONCLUSIONS Early detection of patients with Vaseline penile augmentation and urgent surgery are essential because the best esthetic and functional results can be achieved in the acute period; this is when granuloma does not involve the subdermal but only the subcutaneous layer and local penile flaps can most commonly be used for reconstruction.

Management of Congenital Penile Curvature

PURPOSE The long-term results of the management in adulthood of congenital curvature of the penis (ventral, lateral and dorsal) without hypospadias using 3 different techniques are carefully evaluated based on our experience. MATERIALS AND METHODS A total of 116 patients were operated on for congenital curvature of the penis without hypospadias in adulthood between January 1985 and December 2004 of whom 87 (75%) (mean age 24 years) were available for evaluation by a telephone survey. A total of 54 ventral, 28 lateral and 5 dorsal penile curvatures were operated on with a mean followup of 89 months. Bend was managed with Nesbits procedure in 18, plication in 7 and the Heineke-Mikulitz technique in 62 men. RESULTS There were no significant intraoperative or postoperative complications. Overall 81 of the 87 patients (93.1%) were successfully treated with 1 operation. Curvature recurrence was less common in patients treated with the Heineke-Mikulitz technique. There were no complaints of de novo erectile dysfunction, but 15 men complained of shortening of the penis and 4 experienced decreased sensation of the glans. CONCLUSIONS Although feasible in cases of different types of congenital curvature, in our 20-year experience chordectomy always reduced the bend but patients could never completely straighten the penis by themselves. Surgical correction was reported by patients to be highly successful using the Heineke-Mikulitz technique, and statistical analysis revealed it to be significantly better than plication or the Nesbit procedure in terms of palpable nodules, recurrence and overall satisfaction.

Expression of p21waf1/cip1, p27kip1, p63 and Androgen Receptor in Low and High Gleason Score Prostate Cancer

The aim of this study was to investigate the expression of p21waf1/cip1, p27kip1, p63 and androgen receptor proteins in relation to serum prostate specific antigen levels in low and high Gleason score prostate cancers. Biopsies of patients suffering from prostate adenocarcinoma of low (3 + 3 to 3 + 4) and high (5 + 4 to 5 + 5) Gleason scores (13 cases each group) were immunostained for positive regulators of cell cycle control (p21waf1/cip1 and p27kip1), and essential markers of normal prostate gland ontogeny (p63) and growth (androgen receptor) to find differentially expressed markers of malignant progression. Serum prostate specific antigen levels were also monitored at the time of biopsy and following anti-androgen therapy. All cases except one in each group were androgen receptor positive. P63 and p21waf1/cip1 proteins detected in normal basal cell nuclei were lost in all but one studied tumors respectively. P27kip1 protein, however, was detected in all low Gleason score prostate cancers, but it was found in only 7/13 high score cases. Prostate specific antigen levels, either pre- or post-treatment, did not show strict correlation with the p27kip1 results. The low to high grade dedifferentiation of prostate adenocarcinoma is accompanied with the down-regulation of p27kip1 protein, which may be an important molecular sign of the lost cell cycle control.

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer

We identified and replicated specific combinations of three and four genetic variants that enhance bladder cancer risk in 5049 cases and 5452 controls. Different combinations were relevant in never, former and current smokers. The highest OR was obtained in never smokers (OR = 2.59).

Polymorphisms of xenobiotic metabolizing enzymes in bladder cancer patients of the Semmelweis University Budapest, Hungary

ABSTRACT Polymorphic xenobiotic metabolizing enzymes such as N-acetyltransferase 2 (NAT2) or glutathione S-transferase M1 (GSTM1) are known to modulate bladder cancer risk. As no apparent data were available from Hungary, a former member of the eastern European economic organization, a study was performed in Budapest. In total, 182 bladder cancer cases and 78 cancer-free controls were investigated by questionnaire. Genotypes of NAT2, GSTM1, GSTT1, rs1058396 and rs17674580 were determined by standard methods. Current smokers’ crude odds ratio (OR) (3.43) and former smokers crude OR (2.36) displayed a significantly increased bladder cancer risk. The risk rose by a factor of 1.56 per 10 pack years. Exposure to fumes was associated with an elevated bladder cancer risk (23% cases, 13% controls). Sixty-four % of the cases and 59% of controls were slow NAT2 acetylators. It was not possible to establish a particular impact of NAT2*6A and *7B genotypes (15 cases, 8%, 5 controls, 7%). GSTT1 exerted no marked influence on bladder cancer (negative 21% cases vs. 22% controls). The portion of GSTM1 negative bladder cancer patients was increased (63% cases vs. 54% controls). The SLC14A1 SNPs rs1058396[AG/GG] and the nearby rs17674580[CT/TT] occurred more frequently in cases (79% and 68%) than controls (77% and 55%). The portion of GSTM1 negative bladder cancer patients is comparable with portions reported from other industrialized areas like Lutherstadt Wittenberg/Germany (58%), Dortmund/Germany (70%), Brescia/Italy (66%) or an occupational case-control series in Germany (56%). Data indicate that GSTM1 is a susceptibility factor for environmentally triggered bladder cancer rather than for smoking-mediated bladder cancer.

Changes of protein expression in prostate cancer having lost its androgen sensitivity

ObjectiveThe majority of prostate cancers require androgen hormones for growth, and androgen ablation is an important part of the systemic treatment of advanced prostate cancer. Nevertheless, most of these cancers eventually relapse as they become less sensitive to androgen ablation and anti-androgen treatment. Elucidating the molecular events that are responsible for the conversion of androgen-sensitive cancers to androgen-refractory tumors may reveal new therapeutic opportunities.MethodsIn the present study, we investigated nine androgen-sensitive and nine androgen-refractory prostate cancer samples to evaluate the expression levels of 10 selected proteins that have been implicated in oncogenesis and cancer progression.ResultsOur immunohistochemical data show that three of the investigated proteins (i.e., minichromosome maintenance-2, methylguanine-DNA methyltransferase, and androgen receptor) are expressed at significantly different levels in the androgen-refractory cancer samples than in the androgen-sensitive tumors, whereas the expression levels of the seven other studied proteins (i.e., β-catenin, p27, p21, p16, Ki67, hypoxia-inducible factor 1 alpha, and geminin) are not significantly different regarding the two groups.ConclusionsOur data suggest that the increased expression of minichromosome maintenance-2 and decreased expression of methylguanine-DNA methyltransferase related to androgen receptor are indicative of the androgen-refractory stage in prostate cancer. Further studies are required to determine whether these expression changes play a causative role in the transition of androgen-sensitive to androgen-refractory prostate cancer.

Penis covering and simultaneous urethral replacement by scrotal skin for severe penile and urethral necrosis

ObjectivesPenile strangulation with severe necrosis and concomitant significant tissue loss is a challenging problem for reconstructive surgery. Final reconstruction and tissue augmentation of the resected penis often require multi-step plastic reconstruction.MethodsSevere damage of the phallus with gangrene and septic complication caused by a bronze ring were first conservatively treated to achieve dry gangrene. The glans of the penis, the whole penile skin, and distal third of the corpus spongiosum with the urethra were lost to necrosis, resulting in a missing urethral segment on the penis. Surgery was performed 3 months after removing the metal ring; a one-step skin and urethral reconstruction was done.ResultsGood functional and esthetic results could be achieved by mid-term follow-up.ConclusionIn long-lasting penile strangulation with damaged blood supply, further surgery and treatment are needed in addition to immediate decompression. Most commonly in these situations, amputation seems to be the best and easiest action to be taken. However, our case shows that even in a most severe situation, careful conservative treatment allows preserving the phallus, and subsequently reconstruction enables reaching the best functional and esthetic results.

Az étrend szerepe a húgyúti kövek kialakulásában és megelőzésében

In Hungary and in the developed countries urinary stones occur more often due to nutritional habits, obesity and sedentary lifestyle beside the endocrine and metabolic causes. In the daily urological and family doctor practice prevention should have an important role. Prevention is based not only on body weight control, physical exercise and medical treatment, but on proper diet as well. The nutritional components can change the consistence of urine, causing supersaturation, which is essential in stone formation. Specific nutritional components can either prevent stone formation (increased fluid intake, citrate, magnesium, fruits and vegetables) or either increase stone formation (decreased fluid intake, proteins, carbohydrates, oxalate, salt, increased calcium intake, ascorbic-acid etc). We summarized evidence-based practical dietary suggestions on the primary and secondary prevention of urinary stones. Orv Hetil. 2017; 158(22): 851-855.

A prosztataspecifikus antigén-vizsgacalat elso évtizede klinikánkon (1994-2004)

INTRODUCTION AND AIMS Prostate cancer is the most common malignant tumor in male; its diagnostic algorithm and therapy were investigated. The goal of the study was to compare the data from the first year of clinical use of prostate specific antigen (1994) and the data of 2004. RESULTS During the first decade, the number of prostate biopsies has increased 4.5-fold times. In 1994, 36.2%, while in 2004, 47.5% of the biopsies demonstrated cancer. The average age of the patients, who underwent biopsy, decreased from 69.7 to 62.3 years; however, the average age of patients who suffered from prostate cancer remained constant (70.8 vs. 71.3 years old). CONCLUSION In 2004, along with the earlier used PSA level, the free-PSA and PSA-density was also involved in the diagnostic algorithm. The prostate biopsy is guided by a transrectal US, in contrast to the earlier used blind or transperineal method. Consequently, the effectiveness of the prostate biopsy has improved, but the earlier diagnosis and identification are not assured. The Gleason score of the diagnosed prostate cancer was lower; therefore, more patients were selected for curative surgery. The increased average PSA level reflected a higher number of patients at an advanced stage, which could only be treated palliatively.