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.

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.

Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial–mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes ( IL20RB and WT1 ), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.

Introduction: To evaluate the symptoms, necessity, potential benefits and adverse effects of ureteral stent placement after uncomplicated ureteroscopic lithotripsy. Materials and Methods: This study is retrospective-prospective evaluation a total of 125 patients who underwent ureteroscopic lithotripsy (URSL).Patients were divided into two groups: stented (cases, 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 stone-free 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 mean operative time and mean hospitalization time, mean pain visual analog scale (VAS) score and in use of non-narcotic analgesic. On the day of surgery and until postoperative day (POD) 3 and POD 5, the pain score was much higher among cases 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 treatment.

Objective: Unusual clinical course BACKGROUND: Optviral 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.