O. Stankov - Academia.edu (original) (raw)

Papers by O. Stankov

PRILOZI, 2021

Although kidney transplantation is the best treatment option for end stage kidney disease, it is ... more Although kidney transplantation is the best treatment option for end stage kidney disease, it is still associated with long-term graft failure. One of the greater challenges for transplant professionals is the ability to identify grafts with a high risk of failure before initial decline of eGFR with irreversible graft changes. Transplantation medicine is facing an emerging need for novel disease end point-specific biomarkers, with practical application in preventive screening, early diagnostic, and improved prognostic and therapeutic utility. The aim of our review was to evaluate the clinical application of urinary proteomics in kidney transplant recipients at risk for any type of future graft failure.

PRILOZI, 2020

Introduction: Prostate carcinoma is the most frequent malign neoplasm among men with an ever-grow... more Introduction: Prostate carcinoma is the most frequent malign neoplasm among men with an ever-growing incidence rate. TMPRSS2-ERG fusion transcript leads to the androgen induction of ERG proto-oncogenes expression, representing a high presence of oncogenes alteration among prostate tumour cells. Aim: The aim of this research was to detect and evaluate theTMPRSS2-ERG fuse transcript in the tissues of patients with prostate cancer, and establish a base of material of these samples for further genetic examination. Materials and methods: The research was a prospective clinical study that involved and focused on random sampling of 101 patients (62 with prostate cancer-study group and 39 with benign changes in the prostate-control group). Real time PCR analysis for detection of the TMPRSS2-ERG fusion transcript in prostate tissue was performed and also data from the histopathology results of tissues were used, as well as data for the level of PSA (prostate-specific antigen) in blood. Resul...

Acta Medica Medianae, 2020

Minimally invasive techniques including robotic-assisted and laparoscopic radical prostatectomy h... more Minimally invasive techniques including robotic-assisted and laparoscopic radical prostatectomy have become the preferred approach for operative treatment of prostate cancer. The aim of this study was to evaluate and compare results of laparoscopic radical prostatectomy (LRP) and open retropubic radical prostatectomy (ORRP) for localised prostate cancer, in terms of safety, eficacy and oncological outcome. A total of 123 radical prostatectomies (RPs) for low-risk localised prostate cancer were performed between January 2016 and June 2019 at the University Clinic of Urology Skopje. Of these, 61 (49.6%) were LRP and 62 (50.4%) ORRP, mean patients age was 54 years (33 to 67) Indications for operative procedure included: pathohistological finding of prostate cancer, age ≤ 70 years, PSA<10ng/ml, Gleson score ≤ 7 (3+3 or 3+4), negative bone scintigraphy, stage ≤T2a, N0, M0. All patients were assessed regarding the demographic data, PSA level, Gleason score, operative time, conversion to open surgery for LRP, blood loss, intra and post operative complications, catheter removal, number blood transfusion, hospital stay and oncological outcomes. LRP proved superior to ORRP, resulting in shorter operating time, less blood loss (p < 0.5), shorter time to resumption of oral intake, shorter postoperative hospital stay (p < 0.5), and less analgesic requirements. In terms of oncological outcomes, we observed less positive margins in the LRP group (p < 0.5). Our results indicate that although both operative techniques represent safe procedures, offering good qualiy of operation, in our series, LRP was superior in terms of safety, eficacy and oncological outcomes.

Transplantation, 2020

Introduction: After the first year following kidney transplantation approximately 3-5% of grafts ... more Introduction: After the first year following kidney transplantation approximately 3-5% of grafts fail each consecutive year. Many factors have impact on the graft function and only a few may be modifiable. Monitoring of the graft function by serum creatinine concentrations and estimated glomerular filtration rate (eGFR) are recommended methods for evaluation. The aim of the study was to assess the decline of graft function defined by change in the annual eGFR slope and factors that might affect it. Methods: A total number of 55 adult patients with living donor kidney transplant (LDKT) were included in the study. The inclusion criteria were: first transplantation of one organ kidney, use of living donor related or unrelated (emotionally related spouses) donor. Clinical and biochemical variables, serum creatinine, BUN, protein status, 24 hours proteinuria and body weight were analyzed at 12, 24, 36 and 48 months after transplantation. The Nankivell equation for estimating glomerular filtration rate was used to calculate the slope of renal function over time (1 to 4 years post-transplantayion) by linear regression analysis. Results: Out of 55 kidney transplant recipients 18 (33.3%) were female. The majority of transplants had good function (eGFRNankivell ≥ 60 ml/min) at 1 year. The average GFR at 12 months was 67.81±16.7 mL/min/1.73 m2 with majority of patients at stage 2 of chronic kidney disease classification. Thirty eight patients had eGFR slope <5ml/min/year and 12 patients had a higher slope (>5ml/min/year). Only 5 patients (9%) have graft failure during the period of follow up of 48 months. The average slope decline calculated with linear regression analysis was -3.42 ± 3.2 mL/min/year (range -12.38 – 3.29) (slope ± standard error). Proteinuria was predictive for worsening of the graft function. Rapid progressors have been associated with a higher proteinuria at 24 and 48 months: 0.35 ± 0.39 g/24h, median 0.24 (range 0.11 – 0.43 g/24h) and 0.49 ± 0.59 g/24h, median 0.31 (range 0.14 – 0.48 g/24h), (p=0.044 and p=0.021, respectively). Younger patients have more rapid eGFR slope decline (slope (-7.81 ± 2.12 vs. -2.40 ± 1.3, mL/min/year, p=0,0001). The mean recipient age in the group with stabile eGFR slope was 37.59± 8.7, and in the group with rapid progression was 29.1 ± 8.6 years (p=0.0046). Conclusion: Proteinuria after kidney transplantation has been identified as a risk factor associated with poor graft survival. Younger renal transplant recipients are associated with more rapid decline of the graft function that could be partially explained with their more potent immune response.

European Urology Supplements, 2018

The importance of pathological stage and grade review of primary pT1 bladder cancers after second... more The importance of pathological stage and grade review of primary pT1 bladder cancers after second transurethral resection

European Urology Supplements, 2011

Elocalcitol, a vitamin D3 agonist with Rho-kinase inhibitory effects, prevents functional changes... more Elocalcitol, a vitamin D3 agonist with Rho-kinase inhibitory effects, prevents functional changes of partial urethral obstruction (PUO) in rat detrusor. In patients with BPH, treatment with elocalcitol reduced prostate growth. The aim of the current study was to evaluate the combination of elocalcitol and tolterodine on urodynamic parameters in rats with PUO. Materials & Methods: After Ethical Approval, twenty female Sprague Dawley rats were subjected to PUO and treated (gavage) for 14 days (o.d.) with elocalcitol (75 µg/kg) or vehicle (controls). Cystometries were performed day 15 in awake rats before and after intravenous tolterodine (1, 10, and 100 µg/kg). Statistical methods were t-test, ANOVA, ANCOVA, F-test. results: No differences in body or bladder weights were noted between groups. Tolterodine similarly increased micturition interval, micturition volume and bladder capacity in all rats. Residual volume was increased at 100 µg/kg of tolterodine in controls (p<0.05) but not in elocalcitol-treated rats. Tolterodine had no relevant effect on basal or threshold pressures in any rats. Flow pressure (FP) was unaffected by tolterodine in controls (range 30.3-32.0 cmH2O) but was reduced from 32±2 to 28±2 cmH2O (12 ± 7%) and 25±2 cmH2O (20 ± 7%) at tolterodine 10 and 100 µg/ kg (p<0.05 vs. controls) in elocalcitol-treated rats. Analysis of FP at baseline vs. tolterodine revealed a dose-dependent effect by tolterodine in elocalcitol-treated rats (r=0.25) but not controls (r=0.79; p<0.05). No differences in maximal pressures were noted between groups. Compliance at start of flow (FC) amounted to 0.063±0.009 and 0.081±0.180 ml/cmH2O for vehicle and elocalcitol-treated rats at baseline. Tolterodine 1, 10, and 100 µg/kg increased FC by 21±8%, 23±8%, and 54±15% for controls and by 47±12%, 66±21%, and 131±39% for elocalcitol-treated rats (p<0.05 vs. controls). Maximum tension (MT) amounted to 198±41 (controls) and 317±51 mN/cm (elocalcitol; ns). Irrespective of dose of tolterodine when correlated to bladder weight, elocalcitol-treated rats exhibit higher MT in large bladders (r=0.20) as compared to controls (r =-0.21; p<0.05). The number of non-voiding contractions were similarly reduced by tolterodine in both groups. At baseline, the area under curve (AUC) amounted to 13±2 and 12±1 cmH2O/sec for controls and elocalcitoltreated rats (n.s.). Tolterodine dose-dependently reduced the AUC by 11-16% in controls and 23-30% in elocalctiol-treated rats (p<0.05 vs. controls). Conclusions: Treatment with elocalcitol appears to have additional beneficial effects to tolterodine on flow-related parameters and functional changes during the filling phase in rats with PUO, supporting the use of Rho-kinase inhibitors in treatment of bladder dysfunction associated with outflow obstruction. In addition, elocalcitol-treatment improved effects by tolterodine on bladder compliance.

European Urology Supplements, 2015

European Urology Supplements, 2014

European Urology Supplements, 2013

Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences, 2013

Kidney transplantation (KTx) is the best treatment option in patients with chronic kidney disease... more Kidney transplantation (KTx) is the best treatment option in patients with chronic kidney disease (CKD). Health-economics data favour the KTx in comparison with any type of dialysis procedure, but the multidisciplinary approach and required high level of organisational infrastructure are frequent impediments for its availability in the majority of developing countries. A living donor kidney transplant (LDKTx) programme has been developed in the Republic of Macedonia since 1977 but without a real continuum in the following years. There was a great success with 15 cadaveric kidneys transplanted (1987-1989) followed by an average of 13.5 KTx per year in the period 1996-2011. Because of the scarce organ donation and transplant activities in the majority of Balkan countries the question remains what could be done in order to enable organ transplantation as the basic human right for the best treatment option in patients with CKD. In addition to the possible increase in the number of LDKTx...

The objective of this study is to identify the nuclear expression of the p53 protein in prostate ... more The objective of this study is to identify the nuclear expression of the p53 protein in prostate cancer and to determine its relationship with clinico-pathological variables. Material & methods: The research included 83 patients, 43 of whom are patients with prostate cancer who underwent radical prostatectomy and a control group of 40 patients with benign hyperplasia of the prostate in whom a transurethral resection or a transvesical prostatectomy was undertaken. In all cases the nuclear expression of p53 protein was evaluated. A hystopatological evaluation of the tumour characteristics and the data of the local progression of the cancer were undertaken in the research group. Results: The results show that the expression of the p53 protein does not have an important correlation with the preoperative PSA, but that it is in direct correlation with the malign potential of the cancer (Gleason score, Gleason sum, primary tumour) and with the features of the disease (metastatic lymph nodes, stage of the disease). Conclusion: p53 protein could be used as a valid biomarker in determining the malignant potential of the tumour and the prognosis of the disease. There is no practical use in predicting the extraprostatic extension.

The occurrence of an isolated malignant peripheral nerve sheath tumor (MPNST) of the kidney capsu... more The occurrence of an isolated malignant peripheral nerve sheath tumor (MPNST) of the kidney capsule is extremely rare and its presence may only be expressed by an insidious onset of non-specific and misleading symptoms with a predominance of lower back pain. A computer tomography (CT) scan (as the imaging procedure of choice) will demonstrate the tumor location and its relation to the surrounding structures. Tumor excision in toto is considered the treatment of choice, but it can be hazardous, especially if the tumor is adhering to the surrounding structures. Severe bleeding complications due to the damage of venous structures have to be considered, and establishing hemostasis may pose considerable difficulties. Therefore surgery should be attempted with full precautions and the patient must receive preoperative counseling. If malignancy can safely be excluded, a laparoscopic excision should be considered as an alternative treatment as recurrence is unlikely. Definition of the origi...

International Journal of Proteomics, 2014

Proteome analysis of the urine has shown that urine contains disease-specific information for a v... more Proteome analysis of the urine has shown that urine contains disease-specific information for a variety of urogenital system disorders, including prostate cancer (PCa). The aim of this study was to determine the protein components of urine from PCa patients. Urine from 8 patients with clinically and histologically confirmed PCa was analyzed by conventional 2D PAGE. The MS identification of the most prominent 125 spots from the urine map revealed 45 distinct proteins. According to Gene Ontology, the identified proteins are involved in a variety of biological processes, majority of them are secreted (71%), and half of them are enzymes or transporters. Comparison with the normal urine proteome revealed 11 proteins distinctive for PCa. Using Ingenuity Pathways Analysis, we have found 3 proteins (E3 ubiquitin-protein ligase rififylin, tumor protein D52, and thymidine phosphorylase) associated with cellular growth and proliferation (p=8.35×10-4-3.41×10-2). The top network of functional as...

European Urology Supplements, 2012

Transplantation Proceedings, 2007

The occurrence of malignancies is a well-known serious complication after organ transplantation. ... more The occurrence of malignancies is a well-known serious complication after organ transplantation. Despite the fact that many factors may be involved, the pathogenesis is still unclear. The aim of the present study was to examine the incidence and clinical characteristics of de novo malignancies that arise after renal transplantation over a 13-year experience in a single center in the Balkan Peninsula. During this period, 185 renal transplantations (139 living related and 46 cadaveric) were followed in our department. Overall, 19 malignancies (9.78%) were observed in 15 patients (7.8%). The mean age of these patients was 45 years (range, 21-53 years). Ten patients (55%) developed skin cancers: 8 squamous and 2 basal cell. Kaposi's sarcomas were found in 3 patients (16.6%, 1 visceral form). We also detected 1 breast cancer, 1 seminoma, 1 colon cancer, 1 urogenital-transitional cell-like cancer, 1 renal cell carcinoma, 1 plasmacytoma, and 1 retroperitoneal sarcoma after an ABO incompatible transplantation. All cancers were de novo malignancies that presented at a mean time of 21 months (range, 2-52 months) after surgery. In conclusion, the incidence of malignancy in the present series was similar to that reported elsewhere. The predominance of skin cancers was understandable bearing in mind the sunshine. The appearance of skin malignancies in our group of patients was earlier, more severe, and multiple sites. No cases of posttransplantation lymphoproliferative disorders were observed. Careful clinical examination and long-term screening protocols are needed for early detection and treatment of this life-threatening complication among the transplant population.

Transplantation, 2008

minimizing tissue damages to the hand without interfering with rehabilitation program. Routine bi... more minimizing tissue damages to the hand without interfering with rehabilitation program. Routine biopsies can be taken from the distal sentinel skin graft without disturbing the transplanted hand, minimizing aesthetic sequelae due to visible multiple scars.

Nephrology Dialysis Transplantation, 2013

Introduction and Aims: Renal allograft recipients with thrombophilia are at higher risk for early... more Introduction and Aims: Renal allograft recipients with thrombophilia are at higher risk for early allograft loss, microvascular occlusion and acute rejection with major consequences for allograft survival. The aim of the present study was to evaluate the prevalence of prothrombotic risk factors in patients awaiting renal transplantation and its contribution to patient and transplant outcomes. Methods: All patients with a history of a thromboembolic event, early or recurrent vascular access thrombosis, family history of thrombosis, or multiple miscarriages underwent laboratory screening for thrombophilia. Results: Since the introduction of the screening for hypercoagulable risk factors, 156 candidates for renal transplantation underwent laboratory evaluation. Eighty-eight patients (56%) exhibited at least one prothrombotic laboratory parameter, besides of isolated hyperhomocysteinemia, which confirmed a thrombophilic state. Lupus anticoagulant, anticardiolipin and beta-2-glycoprotein was present in 30%, 18% and 13%, and antithrombin III, protein C and protein S deficiencies in 11%, 8% and 10%, respectively. Factor V Leiden mutation was present in only one patient and prothrombin gene G20210 mutation was not found. Among the 156 patients, 30 underwent renal transplantation and were followed for a median of 199 days (range, 9-418). All patients were on triple immunosuppressive regimen compromising mycophenolate, tacrolimus and prednisone. Thrombophilia was identified in 16 (53%). Seventeen (57%) received perioperative anticoagulation with unfractionated heparin (9 patients with thrombophilia and 8 without laboratory confirmed thrombophilia). Five (30%) of these patients developed perinephric hematomas. Three patients with thrombophilia developed thrombotic complications (2 upper limbs deep-vein thrombosis and 1 allograft artery thrombosis) and 1 patient without thrombophilia developed allograft vein thrombosis, p=0.35. Nine patients developed acute rejection (5 in the group with thrombophilia and 4 in the group without thrombophilia, p=0.87). Mean glomerular filtration rate was similar between thrombophilic and non-thrombophilic patients in the last follow-up (54±27 vs. 47±22 mL/min/1.73m², p=0.35). One graft loss and 1 patient death were observed in each group. Conclusions: Prothrombotic risk factors, especially antiphospholipid antibodies, are highly prevalent in patients awaiting renal transplantation with a clinical or familial history suggestive of thrombophilia, including early and recurrent vascular access failure. Despite pre-transplant screening and perioperative treatment and/or monitoring, thrombotic and bleeding complications are still frequent and severe.

Current Drug Safety, 2013