Risk of bladder cancer in patients with type 2 diabetes mellitus: a retrospective population-based cohort study in Lithuania.

PURPOSE: The objective of our study was to evaluate bladder cancer risk among Lithuanian type 2 diabetes mellitus (T2DM) patients and the effect of antihyperglycemic therapy on bladder cancer risk. METHODS: We analyzed bladder cancer risk in a cohort of patients who were diagnosed with T2DM between 2001 and 2012 in Lithuania. Bladder cancer risk in four groups of antihyperglycemic medication users (insulin-only, metformin-only, sulfonylurea-only, and pioglitazone ± any other drug) was also assessed. Standardized incidence ratios for bladder cancer were calculated. RESULTS: A total of 76,818 patients (28,762 males and 48,056 females) with T2DM were included in the final cohort. In the whole cohort of diabetic patients, 277 bladder cancer cases were observed, compared to 232.75 expected cases, according to bladder cancer rates in the general population (Standardized Incidence Ratio 1.19; 95% Confidence Interval: 1.06-1.34). Higher risk of bladder cancer was found in both men and women; however, in women the risk increase was not statistically significant. We found higher risk of bladder cancer in patients of both sexes diagnosed with T2DM at the age of 50-79 years and also in all groups of different antihyperglycemic medication users. CONCLUSION: T2DM was associated with increased risk of bladder cancer.

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.

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.

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.

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.

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.

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.

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.

Experimental acute pancreatitis induces mitochondrial dysfunction in rat pancreas, kidney and lungs but not in liver.

BACKGROUND/AIMS: Excessive systemic inflammatory response syndrome during severe acute pancreatitis (AP) leads to multiple organ dysfunction syndrome, which is the main cause of death and may be associated with primary mitochondrial disturbances. The aim of our study was to evaluate the role of mitochondria during experimental AP in pancreas and vital organs like kidney, lungs and liver within the first 48 h. METHODS: AP was induced in 39 male Wistar rats by intraductal application of sodium taurocholate (5%, 1.75 ml/kg). Animals were divided into groups reflecting the time from induction of the AP till collection of tissues (control and 1, 3, 6, 12, 24, 48 h). Mitochondria were isolated by differential centrifugation and mitochondrial respiration rates were measured oxygraphically. RESULTS: (1) Mitochondria in pancreas are affected within the first 6 h after onset of AP, (2) kidney mitochondria are affected 24 h after onset of AP, (3) lungs mitochondria are affected within 48 h after onset of AP whereas (4) liver mitochondria remain well preserved within the first 48 h. Severe AP-induced decrease in the oxidative phosphorylation of pancreas, kidney and lungs mitochondria was more pronounced with Complex I-linked (glutamate/malate) than with Complex II-linked (succinate) substrates and was associated with inhibition of Complex I. CONCLUSION: Our data show that the disturbances of mitochondrial energy metabolism in pancreas, kidney and lungs may play an important role in the development and progression of AP as a systemic disease.

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.

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.

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.

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.

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.

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.

Fundamental efforts toward the development of a therapeutic cocktail with a manifold ameliorative effect on hepatic ischemia/reperfusion injury.

OBJECTIVE: Ischemia/reperfusion injury is mediated by various mechanisms. The present study was designed to evaluate the effect of a multiple pharmacological approach toward ischemia/reperfusion injury reduction. METHODS: The left liver lobe of Sprague-Dawley rats underwent normothermic ischemia for 90 minutes after a cocktail (glycine, taurine, alanine, arginine, and prednisolon) intravenous administration. Controls received normal saline. Liver injury (transaminases, histology) and cellular activation [Kupffer cell phagocytosis, production of tumor necrosis factor-alpha (TNFalpha), and prostaglandin E-2 (PGE(2))], as well as microcirculation and leukocyte-endothelial interaction (in vivo microscopy), were assessed. RESULTS: Whereas in controls a substantial increase of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase to 2,341+/-477, 1,442+/-262, and 1,973+/-73 U/L, respectively, was measured eight hours after reperfusion, the cocktail significantly reduced the increase of enzymes by 33-80% (P<0.05). Further, necrosis, index of liver damage, and index of leukocyte infiltration significantly decreased after the cocktail (P<0.05). Moreover, the cocktail improved acinar and sinusoidal perfusion, while the sinusoidal diameters, leukocyte-endothelial interaction, Kupffer cell phagocytic activity, and TNFalpha/PGE(2) serum levels were significantly reduced, the latter by 86% and to 1.64-fold, respectively. CONCLUSIONS: This study depicts that multifaceted pharmacological tackling of ischemia/reperfusion injury is feasible and protects rat liver tissue from warm ischemia/reperfusion injury.

Danshen protects liver grafts from ischemia/reperfusion injury in experimental liver transplantation in rats.

Reperfusion injury remains one of the major problems in transplantation. Free radicals and disturbance of microcirculation are the supposed main contributors. Recent evidence shows that Danshen, a traditional Chinese drug used in vascular diseases, can scavenge radicals and improve microcirculation. This study investigates its effect on liver transplantation (LTx). Before organ recovery, female Sprague-Dawley rats (210-240 g) received intravenous Danshen or the same volume of Ringer solution as control. LTx was performed after 1 h of cold storage. Microperfusion, leukocyte-endothelium interaction and latex-bead phagocytosis were evaluated with in vivo microscopy. Survival, transaminases and histology were assessed. Immunohistology was used for TNF-alpha levels. anova and Fisher's exact test were employed for statistical analyses as appropriate. Survival increased from 60% in controls to 100% (P < 0.05). AST and LDH decreased from 3969 +/- 1255 U/l and 15444 +/- 5148 U/l in controls to 1236 +/- 410 U/l and 5039 +/- 1594 U/l, respectively (P < 0.05). In vivo microscopy revealed decreased leukocyte-adherence and increased blood flow velocity in sinusoidal zones after administration of Danshen (P < 0.05), while latex-bead phagocytosis was found in 60% of controls (P < 0.05). The TNF-alpha index decreased from 2.08 +/- 0.09 in controls to 1.09 +/- 0.09 (P < 0.05). This study clearly demonstrates hepatoprotective effects after experimental LTx, which can be explained via anti-oxidative effects, improved microcirculation and decreased Kupffer cell activation.