Diagnostic Value of GSTP1, RASSF1, AND RASSF2 Methylation in Serum of Prostate Cancer Patients.

PURPOSE: Considering the inadequacy of PSA measurement in the diagnosis of prostate cancer, it is aimed to establish a potential liquid biopsy diagnostic panel. MATERIALS AND METHODS: 39 patients who underwent TRUS-biopsy and 15 healthy volunteers were included. Approximately 15 ml of venous blood samples taken from healthy volunteers and patients before biopsy were separated as plasma. Hypermethylation status of GSTP1 and RASSF1:RASSF2 genes was revealed in cfDNA materials collected from plasma samples. Correlation of this epigenetic change detected in PCa, BPH and healthy volunteer groups with pathology results was examined. RESULTS: Pathology reports of 39 patients included were 13 PCa, 3 ASAP, 3 HGPIN, and 20 BPH. In total, 3 of the patients with PCa had positive GSTP1, 4 had RASSF1 and 9 had positive RASSF2 methylation. It was seen that RASSF2 had the highest sensitivity (69%), specificity (39%) and NPV (80%), while RASSF1 had the highest PPV (30%). When the binary combinations of genes were examined it was observed that the GSTP1:RASSF1 combination had the highest sensitivity (46%), specificity (76%) and NPV (82%). When the methylation of all three genes was examined, it was observed that the sensitivity was quite low (8%), but the specificity (83%) increased significantly. CONCLUSION: Although we observed that the GSTP1 and RASSF1 methylation positivity rates that we examined in our study were higher in patients without prostate cancer, we found that the RASSF2 methylation rate was higher in patients with prostate cancer. randomized controlled studies are needed.

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the betacoronavirus family, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the "cytokine storm" and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences. We identified seven key miRs, which highlight considerable differences between the SARS-CoV-2 sequences, compared with the other viruses. The level of conservation between the five SARS-CoV-2 sequences was identical but poor compared with the other sequences, with SARS showing the highest degree of conservation. This decrease in similarity could result in reduced levels of transcriptional control, as well as a change in the physiological effect of the virus and associated host-pathogen responses. MERS and the milder symptom viruses showed greater differences and even significant sequence gaps. This divergence away from the SARS-CoV-2 sequences broadly mirrors the phylogenetic relationships obtained from the whole-genome alignments. Therefore, patterns of mutation, occurring during sequence divergence from the longer established human viruses to the more recent ones, may have led to the emergence of sequence motifs that can be related directly to the pathogenicity of SARS-CoV-2. Importantly, we identified 7 key-microRNAs (miRs 8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) with significant links to KEGG pathways linked to viral pathogenicity and host responses. According to Bioproject data (PRJNA615032), SARS-CoV-2 mediated transcriptomic alterations were similar to the target pathways of the selected 7 miRs identified in our study. This mechanism could have considerable significance in determining the symptom spectrum of future potential pandemics. KEGG pathway analysis revealed a number of critical pathways linked to the seven identified miRs that may provide insight into the interplay between the virus and comorbidities. Based on our reported findings, miRNAs may constitute potential and effective therapeutic approaches in COVID-19 and its pathological consequences.

Serum antioxidant enzyme levels are decreased in patients with urinary calcium oxalate stones.

PURPOSE: To compare the serum antioxidant enzyme levels between patients with urinary stone disease and healthy volunteers to determine the effect of cellular oxidative stress on urinary calcium oxalate stones formation.Materials & Methods: A total of 51 patients with proven urinary calcium oxalate stones (female 35.3%, mean age: 49.3 years) and 37 healthy subjects (female 45.9%, mean age: 44.1 years) were included. The serum levels of antioxidant catalase, glutathione peroxidase, superoxide dismutase and lipid peroxidation were measured in serum samples taken from the peripheral venous circulation. RESULTS: Mean serum catalase level of patient group was insignificantly higher than healthy subjects (7.54 mmol- H2O2/mg/sec versus 6.16 mmolH2O2/mg/sec, respectively; P = .06) whereas mean superoxide dismutase level (1.56 U/ml versus 3.86 U/ml, P = .047), glutathione peroxidase level (6.70 U/ml versus 8.19 U/ml, P = .022) and lipid peroxidation level (2.35 nmol/ml versus 3.31 nmol/ml, P = .034) of patient group were significantly lower than healthy subjects. Patients with family history of urinary stone disease had significantly lower mean serumlevels of catalase (P = .037), superoxide dismutase (P = .047) and glutathione peroxidase (P = .01), compared with patients without family history. CONCLUSION: The findings of this study provide evidence regarding the role of oxidative stress in the development of urinary calcium oxalate stones. Future clinical trials are necessary to elucidate the actual mechanisms of the calcium oxalate stone formation in the environment with increased oxidative stress.

Applicability of the EORTC risk tables to predict outcomes in non-muscle-invasive bladder cancer in Turkish patients.

OBJECTIVE: To evaluate the consistency of the results of patients who were treated for non-muscle-invasive bladder cancer (NMIBC) in our clinic with the European Organization for Research and Treatment of Cancer (EORTC) risk table. MATERIAL AND METHODS: Data were retrospectively analyzed from 452 patients who had undergone transurethral resection of bladder tumor (TUR-BT) between the years 2002, and 2010 for primary or recurrent NMIBC. Our study had a retrospective design but based on prospective cohort study. Patients were staged according to the 2002 Tumor Node Metastasis (TNM) classification and the 1973 World Health Organization grading system. Recurrence was defined as non-muscle-invasive or muscle-invasive and progression as muscle-invasive tumor determined based on following cystoscopy and TUR-BT results, and confirmed by histopathologic analysis. Patients in the current study were classified into four groups according to the EORTC risk tables. Time to first recurrence and progression was determined for each risk group. RESULTS: Of the 452 patients, 348 were enrolled in this study. The overall mean follow-up period was 55.25 months of all patients. Of 348 patients, 130 (37.4%) and 258 patients (74.1%) had recurrence after treatment at the 1 and 5 year follow-up period, respectively. While 35 (10.1%) and 99 patients (28.4%) progressed to muscle-invasive cancer at the 1 and 5 year follow-up period, respectively. In the multivariate analysis, grade, number, size of the tumor size, and concomitant carcinoma in situ were found to be statistically significant for disease progression and recurrence. CONCLUSION: When EORTC risk tables were comparatively evaluated in our patient population, we can say that EORTC tables predict nearly accurately the clinical course of patients with NMIBC.

The importance of active surveillance, and immediate re-biopsy in low-risk prostate cancer: The largest series from Turkey.

OBJECTIVE: To evaluate long-term outcomes of active surveillance (AS) applied in low-risk prostate cancer patients, and the impact of re-biopsy results on the prediction of progression. MATERIAL AND METHODS: In our clinic, patients who had undergone AS for low-risk localized prostate cancer between the years 2005-2013 were included in the study. Our AS criteria are Gleason score ≤6, prostate-specific antigen (PSA) level <10 ng/mL, number of positive cores <3, maximum cancer involvement ratio <50% each core. Immediate re-biopsy (within 3 months) was performed to 65 patients who accepted AS. Finally, 43 patients who met re-biopsy criteria were included in the study. Prostate biopsy specimens were harvested from 12 cores under the guidance of transrectal ultrasound (TRUS). Re-biopsy was performed within 3 months (1-12 weeks). In re-biopsy, a total of 20 core biopsies were performed including the far lateral (6 cores) and transition zone (2 cores) in addition to standard 12 core biopsy. Our follow-up protocol is PSA measurement and digital rectal examination (DRE) every 3 months within the first 2 years, than every 6 months. Control biopsies was performed one year later and once upon every 3 years to patients whose PSA levels and DREs were normal at follow-up visits. More than 2 tumor invaded cores or 50% tumor in one core, and Gleason score exceeding 6 points were accepted as indications for definitive treatment. Patients were divided into two groups by re-biopsy results and compared according to the time to progression. We have done multivariate regression analysis to predict prognosis by using data on age, PSA level, and detection of tumor in re-biopsy specimens. RESULTS: Patients' median age was 61 years and PSA level was 5 (2.7-9) ng/mL. Tumor was detected in 22 (34%) patients at re-biopsy and they underwent definitive treatment. Additionally tumor was detected in 9 patients, but active surveillance was maintained because their pathologic results met active surveillance criteria. Median follow time was 42 (24-117) months. Definitive treatment was performed in 9 (21%) patients. PSA recurrence was not detected in none of 9 patients during 38 months of follow up. Only the presence of tumor in re-biopsy specimens was found predictor of disease progression in multivariate analysis. CONCLUSION: We think that AS is safe method for low-risk localized prostate cancer patients, if it is performed in compliance with certain criteria and regular follow up, and early re-biopsy can be useful either during early period or long term follow-up.

Analysis of results of recurrence and progression rates of high-grade Ta bladder cancer and comparison with results of high-grade T1.

INTRODUCTION: We aimed to evaluate the long-term recurrence and progression rates in a Turkish population with high-grade Ta and T1 bladder cancer and to determine malign potential of high-grade Ta bladder cancer. METHODS: 191 patients who had non-invasive bladder cancer were evaluated at a single institution between 2005 and 2010. Median follow-up was 55.6 months (13-108). Long-term follow-up results of recurrence and progression rates of high-grade Ta and T1 were analyzed and compared with each other. RESULTS: Of the 191 patients, 143 (74.9%) were high-grade T1 and 48 (25.1%) were high-grade Ta. Of the 143 patients who were high-grade T1, 39 (27.2%) responded to the induction BCG without recurrence. 33 (23%) patients had invasion deep into the muscle layer. 61 (42%) patients had recurred as high-grade T1. Of the 48 patients who were high-grade Ta, 15 (31%) responded to induction BCG without recurrence. 18 (37.5%) patients had recurrence as high-grade Ta. 12 (25%) patients had invasion deep into to the muscle layer. Of all the patients, 13 (7%) patients died of causes related to bladder cancer. In a multivariate analysis, concomitant CIS was statistically significant for the progression of high-grade Ta bladder cancer (p<0.005). CONCLUSIONS: According to the data of the current study, the presence of concomitant CIS in patients with high-grade bladder cancers is associated with a higher risk of progression. There is a need for larger scale multi-institutional studies in order to support the hypothesis that high-grade Ta tumors should be considered as T1 tumors.

Lack of evidence for the association of ornithine decarboxylase (+316 G>A), spermidine/spermine acetyl transferase (-1415 T>C) gene polymorphisms with calcium oxalate stone disease.

Urolithiasis is a complex and multifactorial disorder characterized by the presence of stones in the urinary tract. Urea cycle is an important process involved in disease progression. L-ornithine is a key amino acid in the urea cycle and is converted to putrescine by ornithine decarboxylase (ODC). Putrescine, spermidine and spermine are natural polyamines that are catabolized by a specific enzyme, spermidine/spermine acetyltransferase (SSAT). The single-nucleotide polymorphisms (SNPs) in the intron region of ODC (+316 G>A) and promoter region of SSAT (-1415 T>C) genes have been found to be associated with the polyamines expression levels. The aim of this study was to examine whether the ODC (+316 G>A) intron 1 region gene polymorphism and SAT-1 promoter region (-1415 T>C) gene polymorphisms are potential genetic markers for susceptibility to urolithiasis. A control group of 104 healthy subjects and a group of 65 patients with recurrent idiopathic calcium oxalate stone disease were enrolled into this study. Polymerase chain reaction (PCR)-based restriction analysis was performed for the ODC intron 1 (+316 G>A) region and SAT-1 (-1415 T>C) promoter gene polymorphisms by PstI and MspI restriction enzyme digestion, respectively. The genotype distribution of polymorphisms studied in the ODC intron 1 region (+316 G>A) and SAT-1 -1415 T>C promoter region did not reveal a significant difference between urolithiasis and the control groups (P=0.713 and 0.853), respectively. Furthermore, no significant difference was observed between the control and patient groups for ODC +316 G>A and SAT-1 -1415 T>C allele frequencies (P=0.877 and 0.644), respectively. In conclusion, results of the present study suggest that ODC + 316 G>A and SAT-1 -1415 T>C gene polymorphisms might not be a risk factor for urolithiasis.

Association between IL-1RN VNTR, IL-1ß -511 and IL-6 (-174, -572, -597) gene polymorphisms and urolithiasis.

Urolithiasis is a common multifactorial urological disorder that is characterized by stone formation. Interleukin (IL)-1 and IL-6 are pro-inflammatory cytokines that might be linked with urolithiasis. The single nucleotide polymorphisms within the IL-1 and IL-6 cytokine genes altered the cytokine expression levels. Our aim was to investigate the potential of IL-1ß (-511 C>T), IL-6 (-174 G>C, -572 G>C, -597 G>A) and IL-1RN VNTR gene polymorphisms to be a genetic marker for urinary stone disease. The polymorphisms studied in the promoter regions of IL-1ß and IL-6 genes did not reveal a strong association with urolithiasis when compared to the control group (p = 0.293, 0.871, 0.921, 0.536, respectively). However, a significant difference was observed between control and patient groups for IL-1RN VNTR gene polymorphism (χ(2) = 6.131, d.f. = 2, p = 0.047). Our data provide evidence that IL-1RN VNTR gene polymorphism may be involved in the pathogenesis of urinary stone formation, contributing to genetic susceptibility for urolithiasis.

A case of seminal vesicle cyst associated with ipsilateral renal agenesis diagnosed during an investigation of urinary incontinence.

Seminal vesicle cysts are rare and usually associated with ipsilateral renal agenesis. The diagnosis of seminal vesicle cysts may be delayed or missed because of the non-specific symptoms of this condition. In this study, we aimed to discuss the diagnosis and treatment of a left seminal vesicle cyst that was associated ipsilateral agenesis in a 24-year-old patient who presented to our outpatient department with urinary incontinence. Ultrasonography and magnetic resonance imaging revealed a seminal vesicle cyst measuring 40×45 mm in diameter. Although the patient's symptoms were relieved with cyst aspiration via transrectal ultrasonography, the symptoms recurred 6 months later.

Bilateral Leydig cell tumor of the testis: a case report.

Leydig cell tumors are rare testicular tumors of the male gonadal interstitium. Although uncommon, Leydig cell testicular neoplasms are the most common sex cord-stromal tumors and comprise 1-3% of all testicular neoplasms. This tumor is always benign in children and approximately 90% are benign in adults. In most cases, patients present with an incidental finding of a testicular mass on scrotal ultrasonography during evaluation of hydroceles or varicoceles or during diagnostic workup for infertility. Leydig cell tumors have been primarily managed with radical inguinal orchiectomy. However, conservative management with testis-sparing surgery in younger adults and children were reported in the literature. Here we report a case of bilateral Leydig cell tumor of the testis treated with radical orchiectomy who presented with the complaint of infertilityand no disease recurrence in followup for 9 months. The patient is currently disease-free and under androgen supplemantation for androgen insufficiency. We recommend complete exam and diagnostic workup in patients with infertility and azoospermia.

Tissue reaction of the rat urinary bladder to synthetic mesh materials.

The aim of this study was to assess urinary bladder histopathology induced by the sling materials tension-free vaginal tape (TVT), vypro mesh, and intravaginal slingplasty (IVS). Thirty rats were studied: sham-operated controls, TVT, vypro, and IVS groups. After laparotomy, a 0.5- "e 1-cm piece of mesh was implanted on the anterior bladder wall. The bladder was examined histopathologically after 12 weeks. Inflammation, foreign-body reaction, subserosal fibrosis, necrosis, and collagen deposition were graded. The Kruskal-Wallis and posthoc Dunn tests were used. The sham-operated rats showed no tissue reactions. The TVT, vypro, and IVS groups showed increased inflammation (p = 0.006, p = 0.031, p = 0.001), subserosal fibrosis (p = 0.0001), foreign-body reaction (p = 0.0001), and collagen deposition (p = 0.0001) as compared to sham. Inflammation was more intense in the IVS group as compared to the TVT and vypro groups (p = 0.041, p = 0.028). The bladder presented more increased inflammatory response to IVS than the other meshs. This may play a role in the ultimate outcomes or complications from slings.

Serum adipocytokine levels in prostate cancer patients.

INTRODUCTION: We estimated the circulating levels of adipocytokines such as adiponectin and leptin in nonobese nondiabetic prostate cancer (PCa) patients and compared the results with controls and benign prostate hyperplasia (BPH) patients. MATERIAL AND METHODS: Fifty patients with PCa, 20 patients with BPH and 50 healthy volunteers were entered into the study. Their blood samples were investigated for adipocytokines with the ELISA method. RESULTS: Adiponectin levels were determined as 8.9 and 5.5 microg/ml for the same patients. Leptin concentration was 14.78 ng/ml in organ-confined PCa patients, and 15.24 ng/ml in advanced PCa patients. In control patients, adiponectin and leptin levels were 18.4 and 12.98 ng/ml, respectively. CONCLUSION: Serum adipocytokine levels of PCa patients were significantly different from those of controls and BPH patients who were not obese or diabetic. Therefore, further molecular investigation of these adipocytokines will help understand the mechanism.

Early penile metastasis from primary bladder cancer as the first systemic manifestation: a case report.

Metastatic involement of penis is an exceptionally rare condition. 77% of the metastases are originated from the pelvic region; prostate and bladder are the most frequent primary locations. Retrograde venous route, retrograde lymphatic route, arterial spread, direct extension, implantation and secondary to instrumentation are the mechanisms of metastasis. Approximately two thirds of all penile metastasis are detected at a mean time of 18 months after the detection of the primary tumor and the remaining one third is presented at the same time with primary tumor. Diagnosis is usually made by biopsy and also non invasive methods as MRI or colour-coded duplex ultrasonography. Treatment options in these patients are local excision, partial or complete penectomy, external beam radiation therapy and chemotheraphy. Despite these alternatives prognosis is usually poor.We present a case of urethelial carcinoma of the bladder and coincidental prostate adenocarcinoma with penile metastasis which is presented with priapism 6 months after radical cystectomy as the first systemic manifestation. We performed biopsy initially for staging and the patient underwent MRI showing the extension of the disease. The patient underwent radiotherapy of 56 gy and priapism partially resolved after the treatment. Chemotheraphy was also planned but the patient died 3 months following radiotheraphy.

Manganese superoxide dismutase (Mn-SOD) gene polymorphisms in urolithiasis.

Polymorphism in manganese superoxide dismutase gene (Mn-SOD) is a new approach to identify its probable association with urolithiasis. Oxidative stress may be involved in the development of stone formation in the renal system. MnSOD is one of the primary enzymes that directly scavenges potential harmful oxidizing species. A valine (Val) to alanine (Ala) substitution at amino acid 16, occurring in the mitochondrial targeting sequence of the MnSOD gene, has been associated with an increase in urolithiasis risk. This study was conducted to investigate the association of MnSOD gene polymorphism with the risk of urolithiasis. We investigated the MnSOD in 66 stone-forming adults and 72 healthy volunteers. DNA was isolated from peripheral blood and genotyping was performed with PCR-based methods. Then PCR products were cut by BsaW1. Products were run on 3% agarose gel, 246 bp regions were 1-Ala-9, 164 and 82 bp products were determined as 2 Val-9. Chi-square test was used for comparison between patients and controls. In the control group the homozygote Ala allele was significantly higher than in the patient group (P < 0.01). The distribution of Ala/Val and homozygote Val alleles in the patient group was significantly higher than in the control group (P < 0.05). MnSOD genotype determination may provide a tool to identify individuals who are at risk of urolithiasis. This experiment also provides data about antioxidant status and stone formation.

Laparoscopic unroofing and aspiration-sclerotherapy in the management of symptomatic simple renal cysts.

Simple renal cysts are quite common in adults with an incidence that increases with age. Sclerosant treatment is very common, but the recurrence rate is high. Results are still under investigation for laparoscopic approaches and their long follow-up periods. Between 1998 and 2004, 21 patients were diagnosed with symptomatic renal cysts in our clinics. Initially, all patients underwent aspiration-sclerotherapy with 95% ethanol, the most common sclerosant, under ultrasound, fluoroscopy, or CT guidance. For those with sclerosant therapy failure, the laparoscopic unroofing method was used. Like open surgery, laparoscopic unroofing of the cyst appears to be effective by not only removing part of the cyst wall, but more importantly, by providing adequate drainage of the cyst. After sclerotherapy, 71% of the patients had recurrent pain and cyst on follow-up (at mean 14 months). This group of patients was cured with the laparoscopic unroofing method and there is still no recurrence. We emphasize the unroofing method as better than single session sclerotherapy. And also, laparoscopic unroofing of the cyst is more predictable and has better results than sclerotherapy aspiration.

Increased expression of EZH2, a polycomb group protein, in bladder carcinoma.

INTRODUCTION: Recent experiments have demonstrated that polycomb group gene enhancer zeste homolog 2 (EZH2) is highly expressed in many cancer types. Therefore, we aim to demonstrate EZH2 gene expression in transitional cell bladder cancer. PATIENTS AND METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of EZH2 mRNA levels in healthy and cancerous human bladder specimens. Also, expression of the particular protein was determined by Western blotting and immunohistochemistry to confirm RT-PCR results. RESULTS: Gradually increased expression of EZH2 was detected by mRNA and protein levels in highly advanced bladder cancer specimens. In contrast, 100% of control subjects were negative for EZH2 expression. The expression of EZH2 was more frequent in G3 (92%) than G1-G2 (62-63%) and more frequent in T1-2 (72-85%) than Ta (56%). Western blot analysis results confirm the RT-PCR results. CONCLUSIONS: EZH2 overexpression precedes high frequencies of proliferation and the gradual advance of bladder cancer. These observations suggest that deregulated expression of EZH2 is associated with bladder carcinoma.

Primary adenocarcinoma of the epididymis: case report.

Primary epididymal malignancies are uncommon and usually benign. Benign paratesticular tumors are most commonly adenomatoid, while the most common malignant paratesticular tumors are rhabdomyosarcomas. Approximately 25% of all epididymal tumors are malignant, and of the benign tumors, 60% to 78% are adenomatoid tumors. According to a recent MEDLINE search using epididymis and adenocarcinoma as key words, reports of a primary epididymal adenocarcinoma are extremely rare with only 23 cases in the literature. We report a case of epididymal adenocarcinoma with clinical follow up and metastatic natural history of this rare malignancy.