Search

ObjectivesTo examine the risk of type 2 diabetes in patients with prostate cancer and its association with androgen deprivation therapy (ADT).Design and participantsWe 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.Results27 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).ConclusionThis 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.

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.

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.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.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).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.

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.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.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).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.

Background: The aim of this study was to determine whether type 2 diabetes mellitus and treatment with metformin is associated with prostate cancer risk. Methods: Male patients with diagnosis of type 2 diabetes during the period of 2000 – 2016 were identified in the National Health Insurance Fund database. The prostate cancer cases were identified by pooling these records from the national Cancer Registry. The calculation of prostate cancer stardardized incidence ratios (SIRs) was composed 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: Overall, 64,000 males diagnosed with diabetes in Lithuania between 2000 and 2016 were included in the final cohort. 2,754 prostate cancers were observed versus 3,111.26 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, there were no differences in prostate cancer risk by time since diagnosis of diabetes. Significantly lower risk of prostate cancer also was found in both 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). Conclusions: In this large population-based study we found a significantly decreased risk of prostate cancer among men with diabetes and metformin users. However, the risk of prostate cancer showed no clear trend with diabetes duration and cumulative metformin dose.

ĮvadasHipertermijos indukuojama apoptozė gali lemti vėžinių ląstelių žūtį ir taip praplėsti radijo dažnio abliacijos saugią gydymoribą net iki 10 milimetrų, taip užkertant kelią ligai atsinaujinti. Hipotezei patvirtinti atlikome eksperimentinį tyrimą, kuriuosiekėme įvertinti radijo dažnio abliacijos poveikį inkstų ląstelėms audinyje aplink susidariusią nekrozės zoną bei apibūdintiankstyvus apoptozinius procesus šioje zonoje.MetodaiSukėlus bendrąją endotrachėjinę nejautrą, operuotos aštuonios eksperimentinės kiaulės. Joms atliktos vidurinės laparotomijosir inkstų parenchimos radijo dažnio abliacija. Abliacijos zona ir ją supantys audiniai buvo tiriami Western bloto bei imunohistochemijosmetodais siekiant nustatyti apoptozę.RezultataiValandą po procedūros aktyvuota trečiosios kaspazės 17-kDa dalis nustatyta tranzitorinėje abliacijos zonoje 7–9 mm atstumunuo nekrozės ribos. Tiriant nekrozės zoną bei aplink nepažeistą inksto parenchimą, apoptozės žymenų aktyvumas nebuvonustatytas.IšvadosMes nustatėme, kad po radijo dažnio abliacijos aštuonių milimetrų atstumu nuo nekrozės zonos daugumoje inksto ląsteliųyra aktyvuojama ląstelių žūtį lemianti apoptozė. Tai patvirtina hipotezę, kad po šios procedūros dėl netiesiogiai plintančioterminio poveikio aplink nekrozės zoną gali susidaryti papildomai saugi 8 mm zona.

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.

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.

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.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.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.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.

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.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.(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.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.

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.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.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.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.

Introduction The aim of study was to establish pretreatment and postoperative factors which could predict the early biochemical recurrence after radical prostatectomy. Materials and method 754 patients had undergone radical prostatectomy since January 2002 to December 2008 in our department and were included in this prospective study. Exclusion criteria were: neoadjuvant or adjuvant treatment (radiation or hormonal treatment) and N+. Following parameters were evaluated: age, PSA at time of biopsy, time period from biopsy to operation, biopsy and postoperative Gleason score, stage, high grade intraepithelial neoplasias, perineural invasion. Biochemical recurrence was detected if PSA value after radical prostatectomy was ≥0.2 ng/ml. All factors likely to be predictive were evaluated by univariate analysis (Log-rank test). Multivariate analysis using Cox model was completed for all factors with p value 10 ng/ml (HR 2.45, p = 0.008), pathological stage ≥pT3 (HR 2.371, p = 0.02), postoperative Gleason score ≥7 (HR 2.149, p = 0.049), positive surgical margins (HR 2.482, p = 0.014) and absence of high grade intraepithelial neoplasia in removed prostate (HR 0.358, p = 0.006) are independent factors influencing biochemical recurrence after radical prostatectomy. Conclusion Patients with higher PSA, locally advanced disease, positive surgical margins, and Gleason score ≥7 are at the highest risk for biochemical recurrence.

Objectives To predict bladder outlet obstruction with parameters of non-invasive investigations for patients with symptomatic benign prostatic hyperplasia. Patients and methods A sample of 122 men with moderate to severe lower urinary tract symptoms suggestive of benign prostatic hyperplasia was selected. Transrectal prostate ultrasound, free flow measurement, and transabdominal ultrasound for residual urine were carried out together with digital rectal examination for all patients. All patients underwent urodynamic pressure/flow test. Two groups of obstructed (91 patient) and equivocal/unobstructed (31 patient) were analyzed. Probabilistic model based on logistic regression was developed for prediction of obstruction. Results Various parameters were compared in obstructed and non-obstructed/equivocal groups, highlighting important parameters for obstruction. Correlation analysis indicates higher obstruction dependence on average and peak flow rates and lower dependence on total prostate and transition zone volumes, transition zone index. Binary logistic regression model suggests that average flow rate combined with total prostate volume is the best predictor of obstruction (83% of correct predictions; PPV = 92%; NPV = 52%) in the analyzed sample. The analyzed model suggests that peak flow rate could also be almost equally important parameter instead of average flow rate. Conclusions The study suggests that average/peak flow rate combined with total prostate volume can be used for prediction of obstruction. The developed probabilistic model helps to determine patients who need invasive urodynamic testing for decision on surgical treatment.

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.

Background/Aims: Warm ischemia to liver with subsequent Kupffer cell-dependent pathology is associated with many clinical conditions. Taurine prevents Kupffer cell activation and improves graft survival after experimental cold ischemia and liver transplantation. Thus this study was designed to assess its effects after warm hepatic ischemia. Methods: The left liver lobe of female Sprague-Dawley rats (170–210 g) underwent 60 min of warm ischemia. Animals were given either intravenous taurine or Ringer’s solution 10 min prior to warm ischemia. Transaminases, histology, in vivo microscopy, intercellular adhesion molecules-1 (ICAM-1) expression, TNF-α and tissue hydroperoxide were compared between groups using analysis of variance (ANOVA) or ANOVA on ranks as appropriate. Results: Taurine significantly decreased transaminases and improved histologic outcome. Phagocytosis of latex beads, serum TNF-α levels and tissue hydroperoxide concentrations were also significantly reduced. Stickers in sinusoids and post-sinusoidal venules significantly decreased. In parallel, both leukocyte infiltration and ICAM-1 expression decreased (p < 0.05), while flow velocity of red blood cells as well as sinusoidal perfusion rate were improved (p < 0.05). Conclusion: This study demonstrates that taurine blunts Kupffer cell-dependent hepatic pathology after warm ischemia in vivo via mechanisms including leukocyte-endothelial interaction, microcirculation disturbances and protection against lipid peroxidation.

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.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.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.The disturbances of kidney mitochondrial energy metabolism in experimental model of severe AP can be ameliorated by MB administration.

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.

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.

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.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.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% (P0.05). Further, necrosis, index of liver damage, and index of leukocyte infiltration significantly decreased after the cocktail (P0.05). 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.This study depicts that multifaceted pharmacological tackling of ischemia/reperfusion injury is feasible and protects rat liver tissue from warm ischemia/reperfusion injury.

Mildronate (3-(2,2,2-trimethylhydrazinium) propionate), which is mostly used in cardiological practice and is considered an anti-ischemic drug, was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation. Recently it was shown that the mitochondrial respiratory chain may also be a target for mildronate action. In this study, we aimed to investigate whether mildronate can protect the liver against a 90-min normothermic ischemia/30-min reperfusion-induced mitochondrial dysfunction. Rats were pre-treated for one or two weeks with mildronate (100 mg/kg/day or 200 mg/kg/day) or Ringer solution and subjected to ischemia/reperfusion.We found that ischemia/reperfusion caused a decrease in mitochondrial State 3 respiration rate and in the respiratory control index (RCI), and an increase in State 2 respiration rate with succinate, glutamate + malate and palmitoyl-L-carnitine + malate. One or two weeks of pre-treatment of rats with different doses of mildronate did not reduce the ischemia/reperfusion-induced decrease in the State 3 respiration rate or RCI; however, a one week pre-treatment slightly diminished the increase in the State 2 respiration rate with glutamate + malate substrates. The leakage of the liver enzymes, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase, was similar in both the untreated and pre-treated with mildronate groups. No steatotic livers were observed in any experimental groups after mildronate pre-treatment. In conclusion, 90 min of liver ischemia followed by a 30 min reperfusion has a deleterious effect on rat liver mitochondrial function. Mildronate pre-treatment of rats at doses of 100 or 200 mg/kg/day for one or two weeks did not prevent ischemia/reperfusion-induced mitochondrial dysfunction and liver injury.

Relevant mechanisms of reperfusion injury after liver transplantation are most likely mediated by activated Kupffer cells. Recently, it has been demonstrated that taurine prevents Kupffer cell-activation in vitro. Thus, this study was designed to assess the effects of taurine after liver transplantation. Female Sprague-Dawley rats (210-240 g) were infused with taurine dissolved in normal saline, before organ harvest. Controls were infused with the same volume of normal saline without taurine. Following 4 hours of cold ischemia, liver transplantation was performed. Graft and animal survival, serum transaminases, liver histology, perfusion data of intravital microscopy, blood distribution at reperfusion, and both phagocytosis of Kupffer cells and expression of tumor necrosis factor α (TNF-α) to index cellular activation were investigated. For comparison, both, analysis of variance (ANOVA) and Fisher's exact test were used as appropriate. Results are presented as mean ± SEM. Controls survived in 60% of cases. Taurine improved survival in a dose-dependent manner to 100% (P < 0.05). In controls, mean aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) serum levels increased to 3,260 ± 814; 1,703 ± 432; and 14,071 ± 3,177 U/L, respectively, after transplantation. In contrast, these values were between 20 and 45% of control values after taurine (P < 0.05). Histology taken after transplantation confirmed the significant protective effects of taurine, including the reduction of TNF-α expression. Time until homogeneous reperfusion of the graft improved to 50% of control values (P < 0.05). Further, taurine significantly decreased both phagocytosis of latex beads by Kupffer cells and leukocyte–endothelial cell interaction. In parallel, flow velocity of red blood cells as well as acinar and sinusoidal perfusion improved (P < 0.05). In conclusion, these data show for the first time in vivo that taurine minimizes reperfusion injury after liver transplantation. Decreased leukocyte–endothelial cell interaction and improved microcirculation are the proposed mechanisms, which are most likely Kupffer cell–dependent. (Liver Transpl 2005;11:950–959.)

Currently controversy exists whether bile infection following preoperative biliary drainage has an impact on postoperative complications and mortality rate. The objective of the study was to determine etiology of preoperative bile infection and to evaluate its influence on postoperative complications and mortality after pancreatoduodenectomy.Data on 64 patients, undergoing pancreatoduodenectomy at Kaunas University of Medicine Hospital between 2002 and 2004 were collected prospectively. We evaluated etiology and the impact of bile infection on development of post-operative complications. Patients were divided into groups according to results of intraoperative bile culture.In 31 patients (48.4%) intraoperative bile cultures were negative, while in remaining 33 patients (51.6%) infected bile was documented. Both patient groups were homogenous according to demographic data, preoperative and intraoperative variables. Pancreaticoduodenectomy was performed in 21 patients after preoperative biliary drainage (endoscopic stenting, bilidigestive anastomosis or percutaneous bile drainage), others (n=43) had primary operation. Infected bile was found more often in patients who underwent biliary drainage (p0.0001). Among 43 patients with primary pancreaticoduodenectomy 22 patients underwent endoscopic retrograde cholangiopancreatography without stenting, while remaining 21 had no preoperative endoscopic manipulation. Infected bile was present in 9 patients after endoscopic retrograde cholangiopancreatography (40.9%) and in 4 without preoperative endoscopy (19%). Enterococcus and Escherichia coli dominated in bile cultures of patients with primary pancreaticoduodenectomy, while multiple species (3 and more microorganisms) dominated following drainage procedures. Septic postoperative complications were identified in 26.6% of cases. Infected bile did not influence both overall and septic postoperative complications. Bacteria causing abdominal cavity and wound infections matched bile cultures in 7.7% of cases only.Our data show that infected bile is found more often after preoperative biliary drainage procedures. However, bile infection did not increase statistically significantly the number of postoperative septic complication.

Marius Kincius, Aivaras Matjosaitis Kauno medicinos universiteto Urologijos klinika, Eivenių g. 2, LT-50009 Kaunas El pastas: aivaras.mat@gmail.com Tikslas Perkutaninė nefrostomija siuo metu yra alternatyva atvirajai nefrostomijai ir pirmo pasirinkimo operacija drenuojant virsutinius slapimo takus dėl jų obstrukcijos. Siuo darbu siekta apžvelgti dažniausias priežastis, sukeliancias obstrukcine uropatiją, ir įvertinti perkutaninės nefrostomijos veiksmingumą ir saugumą. Ligoniai ir metodai Retrospektyviai istirti 126 ligoniai, kuriems Kauno medicinos universiteto klinikų Urologijos klinikoje per trejus metus buvo atliktos perkutaninės nefrostomijos. Issiaiskintos dažniausios ligos, kurios komplikavosi vieno ar abiejų inkstų blokada, o slapimo nutekėjimui atkurti buvo atliktos perkutaninės nefrostomijos, taip pat nustatytos dažniausios komplikacijos po sių operacijų. Rezultatai Nuo 2002 m. rugsėjo iki 2005 m. rugsėjo Kauno medicinos universiteto klinikų Urologijos klinikoje is viso buvo atliktos 156 perkutaninės nefrostomijos. Slapimo nutekėjimas 47 ligoniams (37,3%) sutriko dėl nenavikinės slapimo takų obstrukcijos, kitiems 79 (62,7%) – dėl piktybinių navikų. Dažniausios nenavikinės obstrukcijos priežastys buvo inkstų akmenligė, pieloureterinio segmento striktūra ir prostatos nepiktybinė hiperplazija. Pažengusios slapimo pūslės, prostatos ir gimdos kaklelio karcinomos buvo dažniausios navikinės kilmės obstrukcinės uropatijos priežastys. Bendras komplikacijų skaicius siekė 19 (12,2%). Isvada Perkutaninė nefrostomija yra mažai traumuojanti ir visiskai saugi operacija, kurią atlikti turėtų mokėti kiekvienas urologas. Reiksminiai žodžiai: perkutaninė nefrostomija, obstrukcinė uropatija Percutaneous nephrostomy in the treatment of obstructive uropathies at Urology Department of Kaunas University of Medicine Hospital Marius Kincius, Aivaras Matjosaitis Clinic of Urology, Kaunas University of Medicine, Eivenių g. 2, LT-50009 Kaunas, Lithuania E-mail: aivaras.mat@gmail.com Background Percutaneous nephrostomy is an alternative for open surgery and nowadays is the first choice operation for draining the upper urinary tract complicated with obstruction. Patients and methods Between September 2002 – September 2005 at Urology Department of Kaunas University of Medicine Hospital 126 patients underwent percutaneous nephrostomy. Percutaneous nephrostomy was used as a preparatory step towards radical elimination of obstruction and as a palliative treatment for draining the upper urinary tract complicated with obstruction. Results Percutaneous nephrostomy was done to 75 men and 51 women. The reasons for urine flow disorders were removable obstruction of the urinary tract in 47 patients (37.3%) and malignant tumors in 79 patients (62.7%). Bilateral percutaneous nephrostomies were performed for 14 patients. Haematuria appeared in almost all the patients in the early postoperative period. Four patients developed medium or great intensity bleeding (2.6%). In one case segmental renal artery obstruction was performed. The overall complication rate didn’t exceed 13%. Conclusion Percutaneous nephrostomy is a low traumatizing and safe operation which all urologists should be able to perform. Keywords: percutaneous nephrostomy, obstructive uropathy