Single-cell transcriptional profiling of clear cell renal cell carcinoma reveals a tumor-associated endothelial tip cell phenotype.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes to late-stage diagnoses and poor survival. Highly vascularized and immune infiltrated microenvironment are prominent features of ccRCC, yet the interplay between vasculature and immune cells, disease progression and response to therapy remains poorly understood. Using droplet-based single-cell RNA sequencing we profile 50,236 transcriptomes from paired tumor and healthy adjacent kidney tissues. Our analysis reveals significant heterogeneity and inter-patient variability of the tumor microenvironment. Notably, we discover a previously uncharacterized vasculature subpopulation associated with epithelial-mesenchymal transition. The cell-cell communication analysis reveals multiple modes of immunosuppressive interactions within the tumor microenvironment, including clinically relevant interactions between tumor vasculature and stromal cells with immune cells. The upregulation of the genes involved in these interactions is associated with worse survival in the TCGA KIRC cohort. Our findings demonstrate the role of tumor vasculature and stromal cell populations in shaping the ccRCC microenvironment and uncover a subpopulation of cells within the tumor vasculature that is associated with an angiogenic phenotype.

Prostate Adenocarcinoma with Signet-Ring Cells and Features of Mucin: A Clinical Case and Literature Review.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively. Primary signet-ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical Case: In June of 2023, a 54-year-old Caucasian male presented with a complaint of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups, including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma stage IV. Unfortunately, due to the advanced stage of the disease, PE, and third-degree thrombocytopenia, the patient was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results, which may contribute to its late diagnosis. Inconsistent immunohistochemical findings and an unpredictable response to hormonal treatment together pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusions: This study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease, which may positively influence the prognosis.

Efficacy of focal high-dose-rate brachytherapy in the treatment of patients diagnosed with low or favourable: intermediate-risk prostate cancer-a protocol for a randomised controlled trial.

INTRODUCTION: Prostate cancer (PCa) is men's second most predominant cancer worldwide. Because the prostate-specific antigen test is used in diagnostics, PCa is more often diagnosed in the early stages, making radical treatment of the disease possible. However, it is estimated that over a million men worldwide suffer from radical treatment-related complications. Thus, focal treatment has been proposed as a solution, which aims to destroy the predominant lesson that determines the progression of the disease. The main objective of our study is to compare the quality of life and efficacy of patients diagnosed with PCa before and after the treatment with focal high-dose-rate brachytherapy and to compare results with focal low-dose-rate brachytherapy and active surveillance. METHODS AND ANALYSIS: 150 patients diagnosed with low-risk or favourable intermediate-risk PCa who meet the inclusion criteria will be enrolled in the study. Patients are going to be randomly assigned to the study groups: focal high-dose-rate brachytherapy (group 1), focal low-dose-rate brachytherapy (group 2) and active surveillance (group 3). The study's primary outcomes are quality of life after the procedure and time without biochemical disease recurrence. The secondary outcomes are early and late genitourinary and gastrointestinal reactions after the focal high-dose and low-dose-rate brachytherapies and evaluation of the importance and significance of in vivo dosimetry used for high-dose-rate brachytherapy. ETHICS AND DISSEMINATION: Bioethics committee approval was obtained before this study. The trial results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: Vilnius regional bioethics committee; approval ID 2022/6-1438-911.

Incidence, mortality and survival trends of penile cancer in Lithuania 1998-2017.

Background and objectives: The aim of this study was to analyse trends in penile cancer incidence, mortality, and relative survival in Lithuania during the period of 1998-2017. Materials and methods: The study was based on all cases of penile cancer reported to the Lithuanian Cancer Registry between 1998 and 2017. Age-specific rates standardized rates were calculated, using the direct method (World standard population). The Joinpoint regression model was used to provide estimated average annual percentage change (AAPC). One-year and five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. Results: During the study period, the age-standardized incidence rate of penile cancer varied between 0.72 and 1.64 per 100 000, with AAPC 0.9% (95% CI -0.8-2.7). The mortality rate of penile cancer in Lithuania during this period varied from 0.18 to 0.69 per 100 000, with AAPC of -2.6% (95% CI -5.3-0.3). Relative one-year survival of patients, diagnosed with penile cancer improved over the time from 75.84% in period 1998-2001 to 89.33% in period 2014-2017. Relative five-year survival rate of patients, diagnosed with penile cancer changed from 55.44% in period 1998-2001 to 72.90% in period 2014-2017. Conclusions: The incidence rates of penile cancer showed an increasing trend, while mortality rates were decreasing in Lithuania during 1998-2017. One-year and five-year relative survival increased, however, it does not reach the highest scores of Northern European countries.

Androgen-deprivation therapy and risk of death from cardio-vascular disease in prostate cancer patients: a nationwide lithuanian population-based cohort study.

Purpose: The main purpose of this study was to evaluate the risk of CVD mortality in the national cohort of patients diagnosed with prostate cancer and treated with ADT compared with the ADT non-users.Materials and methods: We performed a retrospective cohort study of patients aged 40-79 years and diagnosed with prostate cancer between 1 January 2012 and 31 December 2016 using the Lithuanian Cancer registry data. In total, 13 343 prostate cancer patients were included in the final study cohort who exclusively used gonadotropin-releasing hormone agonists. The primary outcomes that were registered during the follow-up of this study were overall CVD death.Results: There was a higher risk of CVD death in the cohort of patients treated with ADT than in ADT non-users (HR 2.14, 95% CI [1.86-2.45], p < 0.001). Moreover, there was an increased risk of death from ischemic heart disease and stroke (HR 1.42, 95% CI [1.16-1.73] and 1.70, 95% CI [1.18-2.45], respectively) among ADT users. Finally, the risk of CVD-related mortality was highest in the 70-79 age group of ADT users (HR 4.78, 95% CI [3.79-6.04]).Conclusions: This study shows that ADT usage is associated with increased CVD-related mortality risk for patients diagnosed with prostate cancer compared with ADT non-users. The highest mortality risk was found for ischemic heart disease and stroke. CVD-related mortality was increased in the elder group of patients also.

A Case Report and Review of the Literature of Penile Metastasis From Rectal Cancer.

Background: Metastatic involvement of the penis in cases of rectal cancer is exceptionally rare condition. Our clinical case report and review of the literature will contribute in complementing currently limited data on penile metastasis from rectal cancer. Case report: We report a case of a 64-year-old male diagnosed with penile metastasis from rectal cancer. The patient was treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME). However, penile metastasis developed 3 years later, clinically presenting as penile pain and solid formations along the entire length of the penis with visible tumor in the head of the penis. The amputation of penis was performed, and adjuvant chemotherapy was prescribed. The patient survived only 6 months. Conclusion: Penile metastasis from rectal cancer in most cases is a lethal pathology that indicates wide dissemination of oncological disease and has a very poor prognosis. Aggressive surgical treatment is doubtful in metastatic disease as this will negatively affect the quality of life.

Retrospective cohort study of androgen deprivation therapy and the risk of diabetes in men with prostate cancer in Lithuania.

OBJECTIVES: To examine the risk of type 2 diabetes in patients with prostate cancer and its association with androgen deprivation therapy (ADT). DESIGN AND PARTICIPANTS: We performed a retrospective cohort study of patients diagnosed with prostate cancer in the Lithuanian male population between 1 January 2003 and 31 December 2012 who were identified through the Lithuanian Cancer registry. All prostate cancer cases were linked to the National Health Insurance Fund database to obtain information regarding the diagnosis of diabetes mellitus and information on prescriptions of antiandrogens and gonadotropin-releasing hormone (GnRH) agonists. Patients with prostate cancer were followed up until the diagnosis of type 2 diabetes, or 31 December 2017, or date of death, whichever came first. Cox proportional hazard models were used to estimate the risk of type 2 diabetes in patients with prostate cancer with or without ADT exposure. RESULTS: 27 580 men were diagnosed with prostate cancer, out of whom 14 502 (52.6%) did not receive ADT and 13 078 (47.4%) were treated with ADT. The incidence of type 2 diabetes for all patients with prostate cancer was 7.4/1000 person-years, for men on GnRH agonists 9.0/1000 person-years and 5.8/1000 person-years for men on antiandrogens. There was an increased risk of developing type 2 diabetes comparing ADT users and non-users (HR=1.49, 95% CI 1.34 to 1.66). CONCLUSION: This study showed an increased risk of diabetes in patients with prostate cancer treated with ADT in comparison to ADT-free patient cohort. GnRH agonist users showed higher susceptibility, while the group on antiandrogen monotherapy showed no such increase.

Systematic and MRI-Cognitive Targeted Transperineal Prostate Biopsy Accuracy in Detecting Clinically Significant Prostate Cancer after Previous Negative Biopsy and Persisting Suspicion of Malignancy.

Background and objectives: Overdiagnosis, overtreatment, and the need for repeated procedures caused by transrectal ultrasound guided prostate biopsies and their related complications places a heavy burden on healthcare systems. This was a prospective cohort validating study to access the clinical accuracy of systematic and MRI-cognitive targeted transperineal prostate biopsies in detecting clinically significant prostate cancer after a previous negative biopsy and persistent suspicion of malignancy. The primary goal was to assess the ability of multiparametric magnetic resonance imaging (mpMRI) to detect clinically significant prostate cancer with an additional goal to assess the diagnostic value of systematic and MRI-cognitive transperineal biopsies. Materials and Methods: In total, 200 patients were enrolled who had rising serum prostate specific antigen (PSA) levels for at least 4 months after a previous negative transrectal ultrasound (TRUS) biopsy. All eligible men underwent 1.5T prostate mpMRI, reported using the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), followed by a 20-region transperineal prostate systematic biopsy and additional targeted biopsies. Results: Systematic 20-core transperineal prostate biopsies (TPBs) were performed for 38 (19%) patients. Systemic 20-core TPB with additional cognitive targeted biopsies were performed for 162 (81%) patients. Clinically significant prostate cancer (csPC) was detected for 31 (15.5%) patients, of which 20 (64.5%) cases of csPC were detected by systematic biopsy, eight (25.8%) cases were detected by targeted biopsy, and three (9.7%) both by systematic and targeted biopsies. Conclusions: Cognitive mpMRI guided transperineal target biopsies increase the detection rate of clinically significant prostate cancer after a previously negative biopsy. However, in a repeat prostate biopsy setting, we recommend applying a cognitive targeted biopsy with the addition of a systematic biopsy.

LMTK2 as Potential Biomarker for Stratification between Clinically Insignificant and Clinically Significant Prostate Cancer.

A set of prostate tumors tend to grow slowly and do not require active treatment. Therefore, stratification between patients with clinically significant and clinically insignificant prostate cancer (PC) remains a vital issue to avoid overtreatment. Fast development of genetic technologies accelerated development of next-generation molecular tools for reliable PC diagnosis. The aim of this study is to evaluate the diagnostic value of molecular biomarkers (CRISP3, LMTK2, and MSMB) for separation of PC cases from benign prostatic changes and more specifically for identification of clinically significant PC from all pool of PC cases in patients with rising PSA levels. Patients (n = 200) who had rising PSA (PSA II) after negative transrectal systematic prostate biopsy due to elevated PSA (PSA I) were eligible to the study. In addition to PSA concentration, PSA density was calculated for each patient. Gene expression level was measured in peripheral blood samples of cases applying RT-PCR, while MSMB (-57 C/T) polymorphism was identified by pyrosequencing. LMTK2 and MSMB significantly differentiated control group from both BPD and PC groups. MSMB expression tended to increase from the major alleles of the CC genotype to the minor alleles of the TT genotype. PSA density was the only clinical characteristic that significantly differentiated clinically significant PC from clinically insignificant PC. Therefore, LMTK2 expression and PSA density were significantly distinguished between clinically significant PC and clinically insignificant PC. PSA density rather than PSA can differentiate PC from the benign prostate disease and, in combination with LMTK2, assist in stratification between clinically insignificant and clinically significant PC.

Preexisting diabetes, metformin use and long-term survival in patients with prostate cancer.

OBJECTIVE: To assess prostate cancer-specific and overall survival in prostate cancer patients with or without preexisting type 2 diabetes mellitus (T2DM) with regards to metformin use. METHODS: Patients diagnosed with prostate cancer in the Lithuanian population between 2001 and 2005 were identified through the Lithuanian Cancer Registry and followed until 2016, date of death, loss to follow-up or whichever came first. Information regarding the diagnosis of T2DM and antihyperglycemic medications were obtained from the National Health Insurance Fund database. Prostate cancer-specific and overall survival outcomes were analysed using univariate and multivariate Cox proportional hazard models. RESULTS: Out of 6689 men included, 254 (3.8%) had preexisting T2DM. There were 4807 deaths during follow-up, including 2084 from prostate cancer. No differences were found in prostate cancer-specific survival between men with or without T2DM. The risk of overall mortality was higher (HR = 1.24, 95% CI = 1.07-1.43) in diabetic men. Univariate analysis showed cancer stage at diagnosis and age to be significant predictors of survival. After adjustment for age and stage at diagnosis, there was no difference in prostate-specific survival between non-diabetic patients compared to metformin users or metformin non-users. However, overall survival was lower in T2DM patients, with a higher mortality risk for metformin non-users (HR = 1.63, 95% CI = 1.27-2.10). Prostate cancer-specific mortality risk was insignificantly lower in diabetic men on metformin (HR = 0.74, 95% CI = 0.54-1.02). CONCLUSION: There was no difference in long-term prostate cancer-specific survival in patients with or without T2DM. Overall survival was lower in T2DM patients not treated with metformin.

Reduced risk of prostate cancer in a cohort of Lithuanian diabetes mellitus patients.

BACKGROUND: During the past decade, a huge interest was devoted to the type-2 diabetes mellitus and their associations with prostate cancer development. OBJECTIVES: The aim of this study was to determine whether type 2 diabetes mellitus and treatment with metformin is associated with prostate cancer risk. MATERIALS AND METHODS: The cohort was composed of diabetic male patients identified in the National Health Insurance Fund database during 2000-2016 and cancer cases in national Cancer Registry. We calculated standardized incidence ratios (SIR) for prostate cancers as a ratio of observed number of cancer case in people with diagnosis of diabetes to the expected number of cancer cases in the underlying general population. RESULTS: 2754 prostate cancers were observed versus 3111.26 expected within the period of observation entailing an SIR of 0.89 (95% CI: 0.85-0.92). Significantly lower risk of prostate cancer was found in diabetes patients in all age groups, also was in metformin-users and never-users' groups, with higher risk reduction in metformin-users (SIR 0.71, 95% CI: 0.68-0.75) than in diabetes patients never-users (SIR 0.88, 95% CI: 0.80-0.96). CONCLUSION: In this large population-based study, we found a significantly decreased risk of prostate cancer among men with diabetes and metformin-users.

Prostate 3D ultrasound-guided imaging device (HistoScanning) performance detecting clinically significant prostate cancer.

PURPOSE: This is a prospective pair cohort validating study to assess the clinical performance of a 3D ultrasound-guided imaging device (HistoScanning) to detect clinically significant prostate cancer. METHODS: Data was collected prospectively from April 2016 to September 2018 from 200 patients who had their serum PSA levels rising for at least 4 months after previous negative trans rectal ultrasound-guided TRUS biopsy in a single center. All eligible men underwent prostate HistoScanning (PHS) and transperineal template prostate mapping biopsy as our reference standard and additional single targeted biopsy, when PHS device tested positive with a suspicious lesion of ≥0.5 cm3. Our primary goal was to obtain the results of PHS ability to detect clinically significant prostate cancer. Our secondary goal was to acquire data on PHS targeted biopsies. RESULTS: In our study 200 men were enrolled and their mean age was 62 ±5.9 years. The mean number of previous biopsies was 1.51±0.65. The mean volume for PHS index lesion in any one prostate was 1.56 ±2.01 ml. Clinically significant prostate cancer (csPCa) was detected in 41 (20.5%) patients on biopsy. Sensitivity of PHS for detecting csPCa was 61.9% (95% CI 45.64-76.43) with specificity 27.85% (95% CI 21-35.53). Positive predictive value (PPV) and negative predictive value (NPV) for PHS were 18.57% (95% CI 15-22.76) and 73.33% (95% CI 63.45-81.33), respectively. Overall accuracy calculated by AUROC curve was 0.39 (95% CI 0.3-0.47). CONCLUSION: PHS performance results of our study on detecting clinically significant prostate cancer were insufficient to include this ultrasound-guided diagnostic test as standard diagnostic tool.

A Population-Based Analysis of Incidence, Mortality, and Survival in Testicular Cancer Patients in Lithuania.

Background and objectives: The aim of this study was to analyze trends in testicular cancer incidence, mortality, and survival in Lithuania during the period 1998-2013. Materials and Methods: The study was based on all cases of testicular cancer reported to the Lithuanian Cancer Registry between 1998 and 2013. Age group-specific rates and standardized rates were calculated using the direct method (European standard population). The Joinpoint regression model was used to provide the annual percentage change (APC). Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. Results: During the study period, the age-standardized incidence rate of testicular cancer increased from 1.97 to 3.45 per 100,000, with APC of 2.97% (95% CI 0.9 to 5.1). Incidence rate of seminomas changed from 0.71 to 1.54 per 100,000, with APC of 2.61% (95% CI -0.4 to 5.7), and the incidence rate of non-seminomas increased from 0.84 to 1.83 per 100,000, with APC of 4.16% (95% CI 1.6 to 6.8). The mortality rate of testicular cancer in Lithuania during this period declined from 0.78 to 0.51 per 100,000, with APC of -2.91% (95% CI -5.5 to -0.3). Relative five-year survival ratio for the period 2009-2013 was 89.39% (95% CI 82.2 to 94.4). In our study, the overall five-year relative survival increased slightly (10.1%) from 2004-2008 to 2009-2013 (from 79.3% to 89.4%). Conclusions: A moderate increase of testicular cancer incidence has been observed in Lithuania between the years 1998 and 2013, while the mortality rate decreased. The five-year relative survival increased according to different period estimates; however, the results could have been higher if a multidisciplinary approach to diagnostics and management in the concerned centers had been implemented in Lithuania as in other countries.

Sternal resection of a solitary renal cell carcinoma metastasis: a case report and a literature review.

BACKGROUND: Renal cell carcinoma (RCC) may be metastatic, although solitary sternal metastasis of RCC is a rare medical condition. Here we report an unusual case of a 63-year-old male with a solitary sternal metastasis as an initial presentation of clear-cell renal cell carcinoma. MATERIALS AND METHODS: A 63-year-old male presented with a small sternal mass. Chest computer tomography (CT) and a biopsy from the sternal tumour were performed. Histopathological examination revealed the diagnosis of renal clear cell carcinoma metastasis to the sternal bone. On the basis of a subsequently performed abdominal CT the patient was confirmed with a suspicion of a left renal lower pole tumour. Treatment with sunitinib was initiated. Due to the limited response and a growing sternal mass, the patient was admitted to the National Cancer Institute after two cycles of sunitinib therapy. Open left partial nephrectomy was performed followed by the resection of the sternal metastasis two months later. The chest wall was reconstructed with polypropylene mesh combined with transversal rectus abdominis musculocutaneous flap. RESULTS: The postoperative course after the partial nephrectomy was uneventful. The postoperative course of metastasectomy complicated with the right pneumothorax which was successfully treated by insertion of a chest tube. Bleeding from the upper digestive tract also occurred on the seventh postoperative day but was successfully controlled by haemostasis with three 20 ml endoscopic injections of 1:10,000 solution of epinephrine. The patient had been followed up after the surgery for 30 months with biannual chest and abdominal CT scans that showed neither local nor distant recurrence of the disease. CONCLUSIONS: Radical surgical treatment of a solitary renal clear cell carcinoma metastasis may offer the best cancer-specific outcomes and improve the quality of life in some patients.

Evaluation of LRINEC Scale Feasibility for Predicting Outcomes of Fournier Gangrene.

BACKGROUND: Fournier gangrene (FG) is a fulminant necrotizing infection of the perineal, perianal, and periurethral tissues. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scale is used for diagnosis of necrotizing fasciitis. However, data on its relevance and usefulness in FG are lacking. The aim of this study was to evaluate the utility of the LRINEC scale in predicting the outcome of FG. METHODS: This retrospective case study included 41 patents with FG treated at our institution from 2000 to 2013. The patients were divided into survivors and non-survivors. RESULTS: The mortality rate was 22%. The median age (75 vs. 62.5 y; p = 0.013), rate of co-existing diabetes mellitus (66.7% vs. 3.1%; p < 0.001), and median affected skin surface (4% vs. 1%; p < 0.001) were greater in the non-survivors. Seven of nine patients (77.8%) who did not survive (compared with 37.5% who survived) had a polymicrobial infection (p = 0.032). Of all the causative pathogens isolated, Proteus mirabilis was more common in non-survivors (55.6% vs. 6.3%; p = 0.001). The median calculated LRINEC score for survivors was 5 compared with 10 for the non-survivors (p < 0.001). Regression analysis showed that all the aforementioned variables, except for polymicrobial culture, were significant risk factors for predicting death. The area under the receiver operating characteristic curve for the LRINEC score was the highest, 0.976 (95% confidence interval 0.872-0.999; p < 0.0001), and the cut-off value was ≥9 with 93.7% specificity and 100% susceptibility for the prediction of a lethal outcome. CONCLUSIONS: The LRINEC score could be used for prediction of disease severity and outcomes. A threshold of 9 could be a high-value predictor of death during the initial evaluation of patients with FG.

Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis.

OBJECTIVE: The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats. METHODS: AP was induced by administrating sodium taurocholate into the pancreatic duct of male Wistar rats. The rats were divided into three groups: the MB group, MB (5 mg/kg) was injected intravenously 10 min prior to AP induction; the AP group, saline solution was injected intravenously 10 min prior to AP induction; and the sham operation group, isotonic sodium chlorine was used instead of sodium taurocholate. The animals were sacrificed after 24 h. The pancreas and kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods. RESULTS: Intravenous injection of MB did not prevent AP-induced inhibition of pancreatic mitochondrial respiration; however, MB significantly improved kidney mitochondrial respiratory functions with complex I-dependent substrates glutamate and malate. The activity of complex I of mitochondria isolated from AP-damaged kidney was increased after pretreatment with MB. However, MB did not affect AP-inhibited kidney mitochondrial respiration with succinate. MB had no protective effects on amylase activity or on urea content in serum in AP. CONCLUSION: The disturbances of kidney mitochondrial energy metabolism in experimental model of severe AP can be ameliorated by MB administration.

Short ischemia induces rat kidney mitochondria dysfunction.

Renal artery clamping itself induces renal ischemia which subsequently causes renal cell injury and can lead to renal failure. The duration of warm ischemia that would be safe for postoperative kidney function during partial nephrectomy remains under investigations. Mitochondria play an important role in pathophysiology of ischemia-reperfusion induced kidney injury, however relation between ischemia time and mitochondrial dysfunction are not fully elucidated. Thus, the effects of renal ischemia (20 min, 40 min and 60 min) on mitochondrial functions were investigated by using in vitro rat ischemia model. Thus, electronmicroscopy showed that at short (20 min) ischemia mitochondria start to swell and the damage increases with the duration of ischemia. In accordance with this, a significant decrease in mitochondrial oxidative phosphorylation capacity was observed already after 20 min of ischemia with both, complex I dependent substrate glutamate/malate (52%) and complex II dependent substrate succinate (44%) which further decreased with the prolonged time of ischemia. The diminished state 3 respiration rate was associated with the decrease in mitochondrial Complex I activity and the release of cytochrome c. Mitochondrial Ca(2+) uptake was diminished by 37-49% after 20-60 min of ischemia and caspase-3 activation increased by 1.15-2.32-fold as compared to control. LDH activity changed closely with increasing time of renal ischemia. In conclusion, even short time (20 min) of warm ischemia in vitro leads to renal mitochondrial injury which increases progressively with the duration of ischemia.

Evaluation of D'Amico criteria for low-risk prostate cancer.

OBJECTIVE: The aim of the study was to identify the risk of unfavourable disease (≥ pT3 and/or Gleason score ≥ 7) in radical prostatectomy (RP) specimens and biochemical progression-free survival (BPFS) after RP in patients with low-risk prostate cancer detected by D'Amico criteria before surgery. MATERIAL AND METHODS: Between 2004 and 2007, 690 men underwent prostate biopsy and RP at a single university hospital. Of those, 248 patients (35.9%) had low-risk prostate cancer criteria. The endpoints of the study were detection of low-risk (pT2 and Gleason score ≤ 6) or unfavourable (≥ pT3 and/or Gleason score ≥ 7) prostate cancer, and BPFS. The risk of progression was analysed using multivariate Cox regression model and BPFS was established using Kaplan-Meier analysis. RESULTS: The median follow-up was 60 months (1-112 months). pT3 was detected in 14.1%, and Gleason score ≥ 7 in 32.7% of patients. Unfavourable prostate cancer was detected in 37.5% of patients. Overall biochemical relapse rate was 13.6%. The estimated probability of 3-, 5- and 8-year BPFS for all study patients was 90.6%, 88.1% and 77.9%, respectively. Eight-year BPFS was 83.3% for low-risk prostate cancer and 68.2% for unfavourable prostate cancer (p = 0.007). Positive surgical margins (p = 0.0001) and postoperative Gleason score (p = 0.023) were the most significant predictors of biochemical relapse in Cox regression analysis. CONCLUSIONS: The D'Amico criteria may underestimate potentially aggressive prostate cancer in up to 37.5% of patients. Consequently, caution is recommended when the decision concerning the treatment modality is based on D'Amico criteria alone.

Comparison of long-term results after nephron-sparing surgery and radical nephrectomy in treating 4- to 7-cm renal cell carcinoma.

OBJECTIVE: The aim of our study was to compare long-term oncological outcomes following nephron-sparing surgery (NSS) and radical nephrectomy (RN) for renal cell carcinoma (RCC) 4 to 7 cm in diameter. MATERIAL AND METHODS: The study included patients who underwent RN or NSS for RCC 4 to 7 cm in diameter between 1998 and 2009. The studied groups were compared with respect to the patients' age, sex, physical status according to the American Society of Anesthesiologists Physical classification, histological type, stage, tumor size, grade, duration of the operation, and complications. Survival was established using the Kaplan-Meier method. The risk factors for survival were analyzed using a multivariate Cox regression model. RESULTS: During the study, 351 patients underwent surgery: 317 patients (90.3%) underwent RN, and 34 (9.7%), NSS. The compared groups differed with respect to tumor size (P=0.001) and stage (P=0.006). The overall estimated 12-year survival was 53.7% after RN and 55.2% after NSS (log-rank test P=0.437). The 12-year cancer-specific survival in the RN and NSS groups was 69.6% and 80.6%, respectively (log-rank test P=0.198). Pathological stage and patients' age were the major factors affecting both overall and cancer-specific survival. The type of surgery (NSS or RN) had no effect on survival. CONCLUSIONS: Our study showed that nephron-sparing surgery is a safe technique compared with radical nephrectomy that ensures good oncological control in the treatment of renal cell carcinoma measuring 4 to 7 cm and may be proposed as the treatment of choice for renal tumors not only up to 4 cm, but also 4 to 7 cm in size.