The role of cytoreductive nephrectomy in the treatment of patients with metastatic kidney cancer - review article.

The role of cytoreductive nephrectomy (CN), i.e. the removal of a kidney involved by cancer in patients with advanced kidney cancer with distant metastases, is the subject of intense debate among urologists and oncologists. For many years, CN has been considered the gold standard in the treatment of patients at this stage of the disease, especially in patients in good general health with no significant contraindications to surgical treatment. The starting point for questioning the validity of CN was the publication of the results of the cancer du rein metastatique nephrectomie et antiangiogéniques and SURTIME clinical trials (2018 and 2019, respectively), which questioned the validity of surgery in some patients with late-stage cancer. Given the complexity of the disease, the role of removing the involved kidney is the subject of much controversy. In recent years, several studies have been conducted to evaluate the efficacy and safety of nephrectomy in patients with metastatic kidney cancer, resulting in conflicting information regarding the eligibility criteria for patients in different risk groups. The aim of this article is to analyse the available data, provide an up-to-date review of the literature, and discuss the controversies and challenges related to CN in patients with metastatic kidney cancer. The present literature review aims to organize and systematize the current state of knowledge, which may help in making clinical decisions regarding qualification for CN in patients with advanced kidney cancer.

Preoperative cell-free DNA concentration in plasma as a diagnostic and prognostic biomarker of clear cell renal cell carcinoma.

Introduction: Assessment of renal tumour masses is based on conventional imaging studies (computer tomography or magnetic resonance), which does not allow characterisation of the histopathological type. Moreover, the prediction of prognosis in localised and metastatic renal cell carcinoma requires improvement as well. Analysis of circulating free DNA (cfDNA) in blood is one of the variants of liquid biopsy that may improve diagnostics and prognosis issues of patients with renal tumour masses suspected to be renal cell carcinoma. The aim of the study was to assess the diagnostic and prognostic role of preoperative cfDNA concentration in the plasma samples of clear cell renal cell carcinoma (ccRCC) patients. Material and methods: The preoperative plasma cfDNA concentration was assessed in ccRCC patients (n = 46) and healthy individuals (control group) (n = 17). The circulating free DNA concentration was reflected by the 90 bp DNA fragments determined by real-time polymerase chain reaction. Results: The median cfDNA concentration was significantly higher in ccRCC patients (n = 46) compared to the control g roup (n = 17) (2588 ±2554 copies/ml vs. 960 ±490 copies/ml, p < 0.01). In multivariate analysis, the preoperative plasma cfDNA concentration was the significant factor increasing the probability of ccRCC detection (OR: 1.003; 95% CI: 1.001-1.005). The median cfDNA concentration depended on the stage of ccRCC; it was higher in metastatic ccRCC patients (n = 11) compared to non-metastatic ccRCC patients (n = 35) (3619 ±4059 copies/ml vs. 2473 ±1378 copies/ml, p < 0.03). Kaplan-Meier survival analysis demon-strated that patients with high cfDNA values (above 2913 copies/ml) had significantly worse cancer-specific survival (HR: 4.5; 95% CI: 1.3-16.9, log-rank Mantel-Cox test p = 0.015). Conclusions: Preoperative plasma cfDNA concentration has diagnostic and prognostic potential in ccRCC pa-tients.

Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney.

AIMS: Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. METHODS AND RESULTS: We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. CONCLUSION: Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics.

Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype-Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.

PHYTOALEXIN DEFICIENT 4 affects reactive oxygen species metabolism, cell wall and wood properties in hybrid aspen (Populus tremula L. × tremuloides).

The phytoalexin deficient 4 (PAD4) gene in Arabidopsis thaliana (AtPAD4) is involved in the regulation of plant--pathogen interactions. The role of PAD4 in woody plants is not known; therefore, we characterized its function in hybrid aspen and its role in reactive oxygen species (ROS)-dependent signalling and wood development. Three independent transgenic lines with different suppression levels of poplar PAD expression were generated. All these lines displayed deregulated ROS metabolism, which was manifested by an increased H2O2 level in the leaves and shoots, and higher activities of manganese superoxide dismutase (MnSOD) and catalase (CAT) in the leaves in comparison to the wild-type plants. However, no changes in non-photochemical quenching (NPQ) between the transgenic lines and wild type were observed in the leaves. Moreover, changes in the ROS metabolism in the pad4 transgenic lines positively correlated with wood formation. A higher rate of cell division, decreased tracheid average size and numbers, and increased cell wall thickness were observed. The results presented here suggest that the Populus tremula × tremuloides PAD gene might be involved in the regulation of cellular ROS homeostasis and in the cell division--cell death balance that is associated with wood development.

Hormone therapy in combination with radiotherapy in the treatment of prostate cancer: why and in which group of patients?

In recent years, significant development in the treatment of prostate cancer has taken place. One of the most documented methods of treatment in patients characterised by a high risk of progression is a combination of radiotherapy (RT) with long-term hormone therapy (HT). In this group of patients, neither RT alone nor HT alone allows satisfactory outcomes to be achieved, and therefore as monotherapy they are not recommended as optimal methods of treatment. In this review, we summarise arguments for combining radiotherapy with hormonal therapy in high-risk prostate cancer, with an emphasis on the results of phase III trials.

The presence of prostate cancer at biopsy is predicted by a number of genetic variants.

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low-risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.

The use of luteinizing hormone-releasing hormone analogues is still an indispensable element of therapy in castrate-resistant prostate cancer.

Metastatic prostate cancer, which shows progression despite castration testosterone levels, was previously defined as hormone-refractory. This definition has recently been changed to the one presently used - castrate-resistant prostate cancer. Numerous fundamental studies have provided evidence that the development of hormone-refractory prostate cancer is constantly dependent on the concentration of androgens. The aim of the metastatic castrate-resistant prostate cancer (mCRPC) treatment is currently to obtain the lowest possible androgen concentration. The effectiveness of such management has been proven by the results of clinical studies on the latest hormonal and chemotherapeutic medications. In the last two decades, new effective chemotherapeutics have become available on the market: abiraterone, enzalutamide, docetaxel, cabazitaxel, zoldronic acid, denosumab and alpharadin They significantly contribute to extending patients' survival and to improving their quality of life. Therefore, the question arises whether using luteinizing hormone-releasing hormone (LHRH) analogues is still a necessary element of the therapy. A detailed analysis of study regimens involving the above-mentioned medications and of available publications supports the view that LHRH analogues are the basic strategy in the treatment of patients with mCRPC. All clinical trials evaluating new therapies still followed the principle of obtaining castration testosterone levels as a result of using LHRH analogues simultaneously with the new medications.

Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland.

BACKGROUND: The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20-fold). The geographical and ethnic extent of this recurrent allele has not yet been determined. METHODS: We assayed for the presence of the G84E mutation in 3,515 prostate cancer patients and 2,604 controls from Poland and estimated the odds ratio for prostate cancer associated with the allele. RESULTS: The G84E mutation was detected in 3 of 2,604 (0.1%) individuals from the general population in Poland and in 20 of 3,515 (0.6%) men with prostate cancer (Odds ratio [OR] = 5.0; 95% CI: 1.5-16.7; P = 0.008). The allele was present in 4 of 416 (1.0%) men with familial prostate cancer (OR = 8.4, 95% CI: 1.9-37.7; P = 0.005). CONCLUSIONS: The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases. We expect that the G84E founder mutation might be present in other Slavic populations.

Interleukin-6 (IL-6) and C-reactive protein (CRP) concentration prior to total nephrectomy are prognostic factors in localized renal cell carcinoma (RCC).

BACKGROUND: Radical nephrectomy is the gold standard for treatment of renal cell carcinoma (RCC), but even for localized disease the survival rates are still unsatisfactory. Identification of prognostic factorsl is the basis for future treatment strategies for an individual patient. AIM: The aim of our study was to assess the usefulness of the concentration of IL-6 and CRP as prognostic factors in patients after nephrectomy due to localized RCC. MATERIALS AND METHODS: Our prospective study included 89 patients (55 men and 34 women) who had been surgically treated for RCC. The examined group included patients with localized advanced disease (from T1 to T3) with no metastases in lymph nodes (N0), and with no distant metastases (M0). All patients had blood samples drawn three times during the study (one day before surgery, six days after surgery and 6 months after surgery) to evaluate the concentration of CRP and IL-6. In each patient RCC of the kidney was removed during radical nephrectomy. Statistical analysis was conducted using statistica v.7.0. RESULTS: Statistically significant relationships were found between the concentration of CRP before the operation and OS (p = 0.0001). CRP concentration at baseline was statistically significantly correlated with CSS (p = 0.0004). The level of IL-6 assessed before the surgery was significantly correlated with survival times such as OS (p = 0.0096) and CSS (p = 0.0002). The concentration of IL-6 and CRP measured 6 days after surgery and 6 months after surgery were not statistically significantly correlated with survival times. CONCLUSIONS: Results of our study showed that elevated levels of IL-6 and CRP in peripheral blood before surgery of RCC were correlated with worse OS and CSS.

Reasons behind the Delayed Diagnosis of Testicular Cancer: A Retrospective Analysis.

The aim of the present study was to identify the reasons behind the delayed diagnosis of testicular cancer in a group of Polish males diagnosed with this malignancy in 2015-2016. The study included data from 72 patients aged between 18 and 69 years. Based on the median time elapsed to the testicular cancer diagnosis, the study patients were divided into the timely diagnosis group (diagnosis within 10 weeks from initial manifestation, n = 40) and the delayed diagnosis group (diagnosis > 10 weeks from initial manifestation, n = 32). Diagnosis of testicular cancer > 10 weeks after its initial manifestation was associated with less favorable survival (5-year overall survival: 78.1% [95% CI: 59.5-88.9%] vs. 92.5% [95% CI: 78.5-97.5%], p = 0.087). Multivariate logistic regression analysis identified two independent predictors of the delayed diagnosis, age > 33 years (OR = 6.65, p = 0.020) and residence in the countryside (OR = 7.21, p = 0.012), with another two parameters, the lack of a regular intimate partner (OR = 3.32, p = 0.098) and the feeling of shame (OR = 8.13, p = 0.056), being at the verge of statistical significance. All the factors mentioned above should be considered during planning social campaigns aimed at the early detection of testicular malignancies, along with improving the quality and trustfulness of Internet-based information resources.

Baseline CTC Count as a Predictor of Long-Term Outcomes in High-Risk Prostate Cancer.

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at least 5 years. CTCs were enumerated using three different assay formats in 104 patients: the CellSearch® system, EPISPOT assay and GILUPI CellCollector. A total of 57 (55%) patients survived until the end of the follow-up period, with a 5 year OS of 66% (95% CI: 56-74%). The analysis of univariate Cox proportional hazard models identified a baseline CTC count ≥ 1, which was determined with the CellSearch® system, a Gleason sum ≥ 8, cT ≥ 2c and metastases at initial diagnosis as significant predictors of a worse OS in the entire cohort. The CTC count ≥ 1 was also the only significant predictor of a worse OS in a subset of 85 patients who presented with localized PCa at the baseline. The baseline CTC number did not affect the MFS. In conclusion, the baseline CTC count can be considered a determinant of survival in high-risk PCa and also in patients with a localized disease. However, determining the prognostic value of the CTC count in patients with localized PCa would optimally require longitudinal monitoring of this parameter.

Biotechnological Potential of the Stress Response and Plant Cell Death Regulators Proteins in the Biofuel Industry.

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmentally unfriendly. Assuming that the green transformation is inevitable and that new sources of raw materials for biofuels are needed, we decided to study cell death-a natural process occurring in plants in the context of reducing the recalcitrance of lignocellulose for the production of second-generation bioethanol. "Members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field, the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

[Penile cancer--case report and literature review]. / Rak praia--opis przypadku i przeglad literatury.

Penile cancer occurs quite seldom, mostly in men around 60 years of age. However penile squamous cell carcinoma is also observed in younger men. Etiology remains unclear but we can recognize some risk factors such as poor hygiene for example. The authors report a case of a patient who refused treatment in early stages of the disease and was treated only after disease progression. Applied surgical treatment, unfortunately proved to be insufficient and the patient was transferred to complete therapy at the oncology department. This case inspired us to recall the basic diagnostic and therapeutic methods used at the time of diagnosis of the penile tumor

Predictions of cancer incidence in Wielkopolska in 2018.

AIM OF THE STUDY: The cancer incidence in Wielkopolska in 2008 was one of the highest in the country and was higher than in Poland by 21% in men and by 14% in women. We can quantify the future burden of cancer from two different perspectives: the number of new cancer cases due to population change and new cases due to risk change. Making predictions of number of new cancer cases in Wielkopolska in 2018. MATERIAL AND METHODS: These projections of number of cancer cases, age specific rates and age-standardized rates for 2018 (all cancers and the most frequent cancers for men and women) has been based on the historical trends of cancer incidence in Wielkopolska in 1999-2008 and demographical prognosis of Central Statistical Office using the method of Hakulinen and Dyba. RESULTS: There will be over 8000 new cancer cases in men in Wielkopolska in 2018 and over 7000 in women. Compare to the period 2004-2008 the number of cancer cases will increase by 45% for men and by nearly 30% for women. About 2/3 of the increase in Wielkopolska is predicted to be connected with demography change, 1/3 with risk change. CONCLUSIONS: The predicted increase of number of cancer cases in Wielkopolska in 2018 will be the result of: changes in the population (bigger impact of the older age groups), an influence of the risk factors (mainly smoking) and a participation in the screening programs.

Evaluation of the Hydrolysis Efficiency of Bacterial Cellulose Gel Film after the Liquid Hot Water and Steam Explosion Pretreatments.

The influence of bacterial cellulose gel film pretreatment methods on the efficiency of enzymatic hydrolysis was investigated. An increase in the efficiency of enzymatic hydrolysis due to liquid hot water pretreatment or steam explosion was shown. The glucose yield of 88% was obtained from raw, non-purified, bacterial cellulose treated at 130 °C. The results confirm the potential of bacterial cellulose gel film as a source for liquid biofuel production.

Comparison of dose volume histograms for supine and prone position in patients irradiated for prostate cancer-A preliminary study.

AIM: To compare DVHs for OARs in two different positions - prone and supine - for prostate cancer patients irradiated with a Tomotherapy unit. BACKGROUND: In the era of dose escalation, the choice of optimal patient immobilization plays an essential role in radiotherapy of prostate cancer. MATERIALS AND METHODS: The study included 24 patients who were allocated to 3 risk groups based on D'Amico criteria; 12 patients represented a low or intermediate and 12 a high risk group. FOR EACH PATIENT TWO TREATMENT PLANS WERE PERFORMED: one in the supine and one in the prone position. PTV included the prostate, seminal vesicles and lymph nodes for the high risk group and the prostate and seminal vesicles for the intermediate or low risk groups. DVHs for the two positions were compared according to parameters: Dmean, D70, D50 and D20 for the bladder and rectum and Dmean, D10 for the intestine. The position accuracy was verified using daily MVCT. RESULTS: Prone position was associated with lower doses in OARs, especially in the rectum. Despite the fact that in the entire group the differences between tested parameters were not large, the Dmean and D10 for the intestine were statistically significant. In the case of irradiation only to the prostate and seminal vesicles, the prone position allowed for substantial reduction of all tested DVH parameters in the bladder and rectum, except D20 for bladder. Moreover, the Dmean and D50 parameter differences for the bladder were statistically significant. No significant differences between positions reproducibility were demonstrated. CONCLUSION: In patients irradiated to prostate and seminal vesicles, the prone position may support sparing of the rectum and bladder. The reproducibility of position arrangement in both positions is comparable.

Attitudes about Testicular Self-Examination among Polish Males.

INTRODUCTION: Epidemiological data indicate an increased incidence of testicular cancer (TC), making it the most common malignant tumor in men from aged 15-45. Oncological and urological associations recommend that men with specific TC risk factors should regularly perform a testicular self-exam (TSE). The aim of the study was to discover the attitudes among Polish males regarding TSE and factors (environmental, social, educational) that affect intention to perform TSE. METHODS: An original survey containing 21 questions was used to conduct a study among the Polish branch of VW (Volkswagen Poland) employees. RESULTS: A total of 522 fully completed questionnaires were collected. The mean age of the surveyed respondents was 32 years. Information about TC and how to perform TSE was obtained by 34.4% (n = 185) of the men. It was shown that the following factors increase men's intention to perform TSE: TC in their family member (p < 0.05; HR = 5.9; 95% CI: 1.5-23.0), GP's(General Practitioner) recommendations (p < 0.001; HR = 6.8; 95% CI: 3.2-14.3), concern expressed by their partner (p < 0.001; HR = 3.3; 95% CI: 2.1-5.3), and social campaigns (p < 0.001; HR = 2.6; 95% CI: 1.5-4.6). CONCLUSIONS: Approximately half of young polish males do not perform TSE. Access to information on TC prevention is limited. Further action is needed to improve men's awareness of TC and TSE.

Clinical Relevance of Circulating Tumor Cells in Prostate Cancer Management.

Given the low specificity of the routinely used biomarker prostate-specific antigen, circulating tumor cell (CTC) enumeration seems to be particularly useful in the monitoring of prostate cancer. In this review, we focused on a few aspects of CTC enumeration in prostate malignancies: prognostic value in metastatic and non-metastatic tumors, role in the monitoring of treatment outcomes, use as a surrogate marker for survival, and other applications, mostly for research purposes. CTC enumeration, without a doubt, offers an attractive perspective in the management of prostate cancer. However, the vast majority of available data about the role of CTC in this malignancy originate from randomized studies of anticancer agents and do not necessarily translate into real-world clinical practice. Further, most studies on the application of CTC in prostate cancer patients were limited to advanced stages of this malignancy. Meanwhile, the role of CTC in the early stages of prostate cancer, in which some patients may present with occult disseminated disease, is still relatively poorly understood, and should thus be studied extensively. Other obstacles in the widespread application of CTC enumeration in routine clinical practice include considerable discrepancies in the number of cells determined with various commercially available systems.