Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

Polymorphisms of Antioxidant Enzymes SOD2 (rs4880) and GPX1 (rs1050450) Are Associated with Bladder Cancer Risk or Its Aggressiveness.

Background and Objectives: Oxidative stress induced by increased reactive oxygen species (ROS) production plays an important role in carcinogenesis. The entire urinary tract is continuously exposed to numerous potentially mutagenic environmental agents which generate ROS during their biotransformation. In first line defense against free radicals, antioxidant enzymes superoxide dismutase (SOD2) and glutathione peroxidase (GPX1) both have essential roles. Altered enzyme activity and decreased ability of neutralizing free oxygen radicals as a consequence of genetic polymorphisms in genes encoding these two enzymes are well described so far. This study aimed to investigate the association of GPX1 (rs1050450) and SOD2 (rs4880) genetic variants with the urothelial bladder cancer (UBC) risk independently and in combination with smoking. Furthermore, we aimed to determine whether the UBC stage and pathological grade were influenced by GPX1 and SOD2 polymorphisms. Material and Methods: The study population included 330 patients with UBC (mean age 65 ± 10.3 years) and 227 respective controls (mean age 63.4 ± 7.9 years). Single nucleotide polymorphism (SNP) of GPX1 (rs1050450) was analyzed using the PCR-RFLP, while SOD2 (rs4880) SNP was analyzed using the q-PCR method. Results: Our results showed that UBC risk was significantly increased among carriers of at least one variant SOD2 Val allele compared to the SOD2 Ala16Ala homozygotes (OR = 1.55, p = 0.03). Moreover, this risk was even more pronounced in smokers with at least one variant SOD2 Val allele, since they have even 7.5 fold higher UBC risk (OR = 7.5, p < 0.001). Considering GPX1 polymorphism, we have not found an association with UBC risk. However, GPX1 genotypes distribution differed significantly according to the tumor stage (p ˂ 0.049) and pathohistological grade (p ˂ 0.018). Conclusion: We found that SOD2 genetic polymorphism is associated with the risk of UBC development independently and in combination with cigarette smoking. Furthermore, we showed that GPX1 genetic polymorphism is associated with the aggressiveness of the disease.

Bilateral Emphysematous Pyelonephritis Associated with COVID Pneumonia: A Case Report.

BACKGROUND 0ptviral pneumonia and bilateral emphysematous pyelonephritis create a rapid acute respiratory distress syndrome. CASE REPORT A 59-year-old diabetic man with altered awareness was admitted as an emergency due to fever, shivering, and pain in the lap. Based on the accurate diagnosis, we concluded that the patient had bilateral emphysematous pyelonephritis, as well as inflammatory changes in the lung parenchyma caused by coronavirus infection (SARS-CoV-2). Active therapy - nephrectomy - was ruled out due to the late detection of the gas collection in the kidneys, as well as the general condition caused by respiratory symptoms. With symptomatic, supportive, and antimicrobial therapy, such as percutaneous renal drainage, renal abnormalities improved. Unfortunately, the virus-induced parenchymal inflammation progressed and proved fatal. The inflammatory process in the urothelial cell is most likely where the linkage and potentiation of COVID-19 infection and emphysematous pyelonephritis begins. Local inflammation that obstructs the movement of the generated gas is one of the hypothesized processes of emphysematous pyelonephritis. The renal and urothelial tubular cells contain the angiotensin-converting enzyme II (ACE2) receptor, which is used by the SARS-CoV-2 virus to enter human cells and may be a risk factor for simultaneous and direct viral injury to urinary tract cells. Sepsis was most likely caused by viral pneumonia, based on the resolution of changes in the kidneys. CONCLUSIONS The combination of EPN and COVID-19 is difficult to treat. Despite multidisciplinary treatment, it has been linked to a worse prognosis and fatal outcome.

Sex specific associations in genome wide association analysis of renal cell carcinoma.

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

Cyclin D1 and p57 expression in relation to clinicopathological characteristics and overall survival in patients with renal cell carcinoma.

PURPOSE: There is a need for identifying molecular prognostic biomarkers to better predict clinical outcomes in patients with renal cell carcinoma (RCC). This study investigated the pattern of cyclin D1 and p57 expression in RCC patients and evaluated their relation with clinicopathological characteristics and overall survival (OS). METHODS: Immunohistochemistry was applied to paraffin-embedded tissue sections of 74 RCC patients. Two cut-off groups were defined by the fraction of positive cells as follows: ≤10% and >10% positive cells for cyclin D1, and ≤5% and >5% positive cells for p57. RESULTS: Cyclin D1 expression in >10% of positive cells was observed mostly in the clear cell RCC, while p57 expression in ≤5% of positive cells was found in 86% of chromophobe RCC specimens. The higher expression of cyclin D1 and lower expression of p57 were more frequent in grade I-II tumors. OS was associated with unfavorable clinicopathological characteristics. However, cyclin D1/p57 expression did not influence the survival rates. CONCLUSION: Although cyclin D1 and p57 expression did not affect survival rates in RCC patients, proper validation and establishment of the qualitative cut-off point are needed for these tumors.

Stenting versus non-stenting following uncomplicated ureteroscopic lithotripsy: Comparsion and evaluation of symptoms.

Background/Aim: Currently, ureterorenoscopic (URS) stone fragmentation and removal is the treatment of choice for managing ureteral stones, especially mid and distal ones and is advocated as initial management of ureteric stones. The aim of this work was to evaluate the symptoms, necessity, potential benefits and adverse effects of ureteral stent placement after uncomplicated ureteroscopic lithotripsy. Methods: This retrospective-prospective study evaluated a total of 125 patients who had underwent ureteroscopic lithotripsy (URSL). The patients were divided into two groups: stented (59 patients) and unstented (controls, 66 patients). The outcomes measured and compared between the two groups included: stone free rate, postoperative patient pain validated by scale, lower urinary tract symptoms (LUTS), the need for unplanned hospital care, stent related complications, and functional recovery in the form return to normal physical activities. Results: A successful outcome, defined as being stonefree after 12 weeks, was achieved in all 125 (100%) patients. The stone-free rate showed no significant differences between the two groups. LUTS was frequent complaint in the stented group, with statistically significant difference in the domain of frequency/urgency (p = 0.0314). There was a statistically significant difference between the groups in the mean operative time and mean hospitalization time, mean pain visual analog scale (VAS) score and in the use of nonnarcotic analgesic. On the day of the surgery and until postoperative day 3 (POD 3) and postoperative day 5 (POD 5), the pain score was much higher among stented patients than among the controls (p = 0.0001) and non-narcotic analgesic use (p = 0.001) was frequently required in the stented group. Conclusion: Routine placement of ureteral stent after URSL is not mandatory and may be associated with stent side effects. Uncomplicated URSL is safe without stent placement after the treatment.

Management of calculus anuria using ureteroscopic lithotripsy as a first line treatment: its efficacy and safety.

PURPOSE: To present our experience with emergency ureteroscopic lithotripsy (URSL) for ureteral calculi associated with acute kidney injury (AKI). MATERIALS AND METHODS: We retrospectively evaluated the 61 patients consisted of 90 ureteral units (UU), who underwent URSL. The cause of anuria was bilateral calculus obstructions in 29 cases, and unilateral calculus obstruction with, absent, nephrectomized contralateral kidney in 32 cases. In the case of bilateral synchronous ureteric calculi same-session bilateral ureteroscopy (SBBU) was done. The duration of anuria varied between 12 to 72 hours. At the end of the procedure, ureteral stent was systematically left in place in all patients. Surgery was performed 6-12 hours after admission to hospital. Patients were followed at least 1 month postoperatively. RESULTS: The stone free rates (SFR) were determined as baseline, on the first post-operative day, and as overall on the 30 days after procedure. The greatest success was achieved in the distal localization of stones up to 10 mm (93%). Renal function returned in 51 (83.6%) patients within 7 days. In 18 (29.5%) patients [18 (20%) UU] we performed second procedure as extracorporeal shockwave lithotripsy in 16.7% and open surgery in 2.2%. In 43 (70.5%) patients URSL was a successful therapeutic approach in dealing with pain, obstruction and calculus. CONCLUSION: Calculus anuria is a medical emergency that requires rapid diagnosis and prompt treatment for the purpose of decompression. URSL is the proper method of choice for selected patients and can be performed safely and has high success rates with minimal morbidity.

Rare locations of metastastatic renal cell carcinoma: a presentation of three cases.

INTRODUCTION: Metastatic renal cell carcinoma (RCC) frequently spreads not only to neighboring lymph nodes, but also to distant organs, including the lungs, liver, bones and brain. CASE REPORT: We presented three cases of RCC with colon metastasis. In the first, 63-year-old patient, after left nephrectomy followed with lyphadenectomy in paraaortic lymph node, left hemicolectomy was done due to RCC metastasis in rectosigmoid colon. In the second, 35-year-old patient, left radical nephrectomy was followed two years later with partial right nephrectomy, lung metastasectomy, small bowel and coecum resection and right orchiectomy all as separate procedures in different time intervals. The patient died from brain and bone metastases two years after the first surgery. The third, 35-year-old patient, had right nephrectomy followed by repeted lymphadenectomies after 6, 12 and 24 months. Four years later RCC spreaded to coecum and right hemicolectomy was performed. CONCLUSION: RCC treated with nephrectomy should be carefully followed up with imaging methods as a proper treatment of RCC metastases to distant organs could be important for a patient survival.