Percutaneous Nephrostomy as a Procedure in the Treatment of Urinary Tract Obstruction - Experiences in the University Clinic of Urology in Skopje.

INTRODUCTION: Obstructive uropathy encompasses various urinary tract obstructions, leading to changes in urine flow, kidney pressure, and impaired kidney function. Predicting renal recovery from obstructive uropathy, can be challenging and necessitates treatment, as in percutaneous nephrostomy (PNS) drainage. The choice of drainage method depends on patient-specific factors and local expertise. According to the data for the Republic of North Macedonia, in the register of the European Renal Association, in the last few years, there has been an increase in the percentage of patients with obstructive nephropathy from 7.6% to 8.9% who end up on a chronic hemodialysis program. Prompt relief from urinary tract obstruction is essential to preserve renal function and prevent complications. The aim of this study is to present our initial data analysis of recent experience in the use of nephrostomies as a method for temporary or long-term resolution of obstructive nephropathy, in terms of safety and success in preserving kidney function and reducing the number of patients on hemodialysis. MATERIALS AND METHODS: This study analyzed the medical records of 24 patients with obstructive uropathy who underwent PNS placement. Data were collected for the type and degree of obstruction from the ultrasonographic examination. A pig tail nephrostomy was used, with a dilator, guided under ultrasound and controlled with contrast and fluoroscope. Obstructive nephropathy was defined as an elevation of the serum creatinine > 109 µmol/L, before the intervention. Glomerular filtration rate (GFR) was calculated according to the formula CKD epi in ml/min. Each placement of the PNS was considered as an individual procedure and the data of 38 placed nephrostomies were analyzed. We compared the laboratory analyses from the day before (D0) PNS placement and on the seventh day (D7) after PNS placement. The reduction of values for red blood cells (RBC) and hemoglobin (Hb) baseline values from D0 to D7 and the need for transfusion after the procedure were defined as a complication-bleeding. The increase in total counts of the white blood cells (WBC) and C-reactive protein (CRP) from the baseline values from D0 to D7 were defined as a complication-infection. Standard statistical methods were used for data processing. RESULTS: Most patients, 17 (70%), had malignant disease as the cause of obstruction. Unilateral obstruction was more common, detected in 24 (63%) of procedures, with a high degree of hydronephrosis. Obstructive nephropathy, marked by elevated serum creatinine, was observed in 23 (60%) cases before PNS placement. Complications included bleeding and infection but did not result in any fatalities. When comparing the laboratory analysis before PNS placement (D0) and seven days later (D7), a statistically significant decrease in serum creatinine (225±161 vs. 162±145, p=0.005) and an increase in GFR (47±39 vs.59±34, p= 0.005) were observed. CONCLUSION: Percutaneous nephrostomy is a safe and effective treatment option for urinary tract obstruction, especially in patients with malignancies. Continuous monitoring is essential to assess long-term complications and the longevity of PNS functionality. This procedure offers a significant benefit in preserving renal function and minimizing the need for hemodialysis in these patients.

Laparoscopic Donor Nephrectomy in the Republic of North Macedonia.

Introduction: Hand-assisted laparoscopic living donor nephrectomy has become the technique of choice for living donor kidney donations. Since 2018, 30 procedures have been performed at our clinic using this technique. The goal of this comparative analysis was to determine how surgical technique, specifically, hand-assisted laparoscopic living donor nephrectomy with hand assistance may affect early graft function when compared to open classical nephrectomy. Material and methods: Retrospective analyses were performed, comparing the two techniques of kidney donation. Kidney transplantation was performed with the open standard technique in both groups. The primary outcome was early graft function, and levels of urine output, and plasma creatinine were analyzed at three time points. A secondary outcome was the quality of the operative technique, which was determined by the time of warm ischemia, blood loss, and duration of surgery. Additionally, we noted all complications, length of hospital stay, and patient satisfaction. Results: In terms of warm ischemia time, there was no statistically significant difference between donors in both groups. It is important to note that in 2 recipients from Group II we did not observe diuresis at the conclusion of the operation. The recipients' diuresis was 515 ml ± 321SD in group I and 444 ml ± 271SD in group II. At 3, 12, and 36 hours postoperatively, there were statistically significant differences in the average serum creatinine values (p 0.05) in favor of group I. Similar results were observed in the second time measurement at 12 h and the third time measurement at 36 h for serum urea levels in recipients. The difference in serum urea values between the recipients in the groups at the first measurement (3h) following surgery was not statistically significant. Conclusion: Hand-assisted laparoscopic donor nephrectomy is recognized as a safe and effective treatment. Donors in this situation have a different profile from other surgical patients; hence, they do not undergo surgery due to their own medical condition but for an altruistic reason, and with hand-assisted living donor nephrectomy. Such patients receive all the advantages of minimally invasive surgery. The two main objectives of a donor nephrectomy are to give the recipient the best possible kidney and to ensure the donor's complete safety.

Obturator Nerve Block for Transurethral Resection of Bladder Tumors.

Background: Bladder tumors are identified and treated using a surgical procedure called as transurethral resection of bladder tumors (TUR-BT). During TUR-BT resection, stimulation of the obturator nerve may cause violent adductor muscle spasms. The "obturator reflex," as this disorder is known, generally causes the legs to move inadvertently (leg jerking). Since this condition can cause several complications, it is preferable to avoid it. Objective: In this study, we investigated the effectiveness of spinal anesthesia combined with obturator nerve block or general anesthetic without muscle relaxant in preventing adductor muscle spasm during TUR-BT procedures. Methods: Forty consecutive patients were enrolled in a prospective observational evaluation and divided into two groups. Patients in Group I underwent spinal anesthesia along with an obturator nerve block, while those in Group II underwent general anesthesia without a neuromuscular relaxant. The following details were recorded: time for obturator block performance, the severity of the motor blockade, the length of the procedure in both groups because a probable adductor spasm might make it more difficult. The level of the surgeon's pleasure was noted throughout the surgery. Additionally, the patient's satisfaction and any issues that may have arisen were documented (the incidence of vascular puncture, hematoma, nerve damage, and visceral injury was noted). Results: Block performance time in Group I was 4.8±0.5 minutes, whereas it was 5.0±0.3 minutes in Group II. The ease of access for the two groups was the same. Group I demonstrated increased patient and surgeon satisfaction with a general anesthesia without neuromuscular relaxants and an obturatorius nerve block. Mean surgical time did not differ between the groups.There were no complications in either group. Conclusion: During such operations, routine use of ONB in combination with spinal anaesthetic or general anesthetic without a neuromuscular blocker can enhance oncological outcomes for patients, reduce complication rates, and extend the period of time spent living without disease.

AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study.

OBJECTIVE: This study aimed to measure the AHNAK2 urinary levels in bladder cancer patients. MATERIAL AND METHODS: This prospective case-control study enrolled 67 participants between January and March 2019 and were categorized into bladder cancer group (n=37), with histologically proven bladder can cer, and control group (n=30), with histologically verified benign lesions or with no bladder cancer indica tion during follow-up. Urine samples of 15 mL were collected in the mid-morning before cystoscopy/surger y and an enzyme-linked immunosorbent assay was performed as per the manufacturer's protocol. Bladder malignancies were classified according to the World Health Organization Tumor Classification. Group's associations were evaluated with the Student t-test, Spearman's rank correlation, and Mann-Whitney U test, while receiver operating curve was plotted for assessing the test's performance. RESULTS: Mean age of the bladder cancer group was 66.41 years (standard deviation=10.04, range=43-82 years) and the control group was 59.67 years (standard deviation=10.44, range=38-77 years). All bladder cancers were of the urothelial histotype, with the following pT distribution: pTa/papillary urothelial neoplasm of low malignant potential (n=19; 28.4%), Primary tumor (pT) in situ (n=4; 6%), pT1 (n=7; 10.4%), and pT≥2 (n=7; 10.48%). Mean AHNAK2 levels were higher in bladder cancer patients 49.08 pg/mL (standard deviation=114.91) compared to controls 5.28 pg/mL (standard devia tion=6.65), P < .05). Significant differences were noted between non-invasive bladder cancer (n=23; mean=7.14 pg/mL; standard deviation=7.26) and invasive bladder cancer (n=14; mean=117.99 pg/mL; standard deviation=168.08) and between non-muscle invasive bladder cancer (mean=23.19 pg/mL; standard deviation=66.93) and muscle-invasive bladder cancer (mean=160.05 pg/mL; standard devia tion=199.65) (P < .001). The result of the assays was given as follows: sensitivity: 64.19%, specificity: 66.67%, positive predictive value: 22.07%, negative predictive value: 92.37%, area under curve: 0.695, and 95% CI: 0.57-0.82. CONCLUSION: AHNAK2 protein could be used as bladder cancer surveillance biomarker. The inclusion of AHNAK2 levels in stratification nomograms might reduce the number of unnecessary cystoscopies.

Urinary Proteomics in Kidney Transplantation.

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.

Radiation Exposure of Surgical Team During Endourological Procedures: International Atomic Energy Agency-South-Eastern European Group for Urolithiasis Research Study.

Introduction: Fluoroscopy-guided endourology procedures require proper radiation protection to minimize radiation risk. This multicenter study aimed at investigating radiation protection practice and related radiation exposure of operating team members. Materials and Methods: Six endourology centers from the South-Eastern European Group for Urolithiasis Research answered questionnaires and collected data of 315 procedures performed within a 3-months period, with simultaneous measurement of dose to staff and dose area product (DAP) to patient. A pair of calibrated personal dosimeters, one for body and one for eye-lens dose, was worn by all key staff members. Dosimeters were centrally calibrated, measured, and analyzed. Results: The annual workload ranged from 173 to 865 procedures per center. Practice of personal dose monitoring and use of radiation protection shielding was found to be inconsistent. Lead aprons and thyroid collars were used by all, whereas protective eyewear was used in only half of centers. Due to the regular use of protective aprons, the whole-body dose of all 44 monitored staff members was safely below the regulatory dose limits. Eye-lens dose of 17 (14 urologists and 3 assisting staff) was above the dosimeter detection level, and dose per procedure varied from <10 to 63 µSv. The highest annual eye-lens dose of 13.5 mSv was found for the surgeon in the busiest department by using an over-the-couch X-ray tube without a ceiling suspended screen. Working closer to patient body with no protection resulted in a six-time higher eye-lens dose per DAP for a surgeon compared with others in the same center. Lower eye-dose per procedure was associated with lower DAP to patient and with the use of an under-the-couch tube, lower fluoroscopy pulse rate, collimation, fluoroscopy time, and acquired images. Conclusions: The study results call for the need to establish standard protocols about use of fluoroscopy during endourology procedures and to increase radiation protection knowledge and awareness of surgical staff.

Management of Multiple Renal Arteries and Unusual Venous Anatomy During Kidney Transplant: From a Simple Technical Problem to a Graft-Saving Procedure.

OBJECTIVES: Incidence of vascular anomalies in donor kidneys varies from 18% to 30% and presents a challenge for a transplant surgeon in kidney transplant. Here we present our personal experience for man - agement of the complicated and unexpected cases. MATERIALS AND METHODS: A total of 250 kidney transplants (226 living, 24 deceased) were performed in a period of 24 years; mean donor age was 55 years (range, 25-86 years), and mean recipient age was 38.6 years (range, 14-66 years). We analyzed the surgical techniques, complications and outcomes, rejection episodes, kidney function, and graft and patient survival rates. RESULTS: Of 250 nephrectomies, 209 had a single artery (83.6%), 34 had 2 arteries (13.6%), and 7 had 3 arteries (2.8%). Of 34 double arteries, 14 had 2 main arteries, 15 had a main and a polar artery, and 5 had an aortic Carrel patch after deceased donation. According to the size, type, and position, the anastomoses were performed with branches of hypogastric, epigastric inferior, iliac external, and main renal artery, intracorporeally or in bench surgery. Regarding veins, 1 double inferior vena cava, 1 left-side inferior vena cava, 4 retroaortic, 2 circumaortic, 10 large lumbar veins draining into the left renal veins, and 8 cases with 2 or more different size renal veins were managed. In 9 cases with short right renal vein, an extension with vena cava (a "Barry cavoplasty") was performed in deceased donor organs. No serious surgical complications related to vascular anomalies were observed. There were no statistical differences in 1-, 6-, and 12-month graft survival rates between the groups with or without vascular anomalies. CONCLUSIONS: Vascular anomalies should no longer be considered a contraindication for transplant, if careful anastomosis is performed in every case to avoid ischemia and further complications. Therefore, management of vascular anomalies could be a graftsaving procedure.

Radiation exposure of patients during endourological procedures: IAEA-SEGUR study.

Fluoroscopy is increasingly used to guide minimally invasive endourological procedures and optimised protocols are needed to minimise radiation exposure while achieving best treatment results. This multi-center study of radiation exposure of patients was conducted by the South-Eastern European Group for Urolithiasis Research (SEGUR), in cooperation with the International Atomic Energy Agency. Seven clinical centers from the SEGUR group collected data for 325 procedures performed within a three-months period, including standard percutaneous nephrolithotomy (PCNL), mini PCNL, retrograde intrarenal surgery (RIRS), semirigid ureterorenoscopy (URS) and flexible URS. Data included: air kerma area product (PKA), air kerma at the patient entrance reference point (Ka,r), fluoroscopy time (FT), number of radiographic images (N) and fluoroscopy pulse rate, as well as total procedure duration, size and location of stones. Data were centrally analysed and statistically compared. MedianPKAvalues per center varied 2-fold for RIRS (0.80-1.79 Gy cm2), 7.1 fold for mini-PCNL (1.39-9.90 Gy cm2), 7.3 fold for PCNL (2.40-17.50 Gy cm2), 19 fold (0.13-2.51 Gy cm2) for semi-rigid URS and 29-fold for flexible URS (0.10-2.90 Gy cm2). LowerPKAandKa,rwere associated with use of lower FT,Nand lower fluoroscopy pulse rate. FT varied from 0.1 to 14 min, a small fraction of the total procedure time, ranging from 10 to 225 min. HigherNwas associated with higherPKAandKa,r. Higher medianPKAin PCNL was associated with the use of supine compared to prone position. No correlation was found between the concrement size and procedure duration, FT,PKAorKa,r. Dose values for RIRS were significantly lower compared to PCNL. The maximumKa,rvalue of 377 mGy was under the threshold for radiation induced skin erythema. The study demonstrated a potential for patient dose reduction by lowering FT andN, using pulsed fluoroscopy and beam collimation.

Bacterial spectrum and antibiotic resistance of urinary tract infections in patients treated for upper urinary tract calculi: a multicenter analysis.

The purpose of this study is to collect information on the bacterial resistance to antibiotics of bacteria isolated from urine cultures of patients treated for upper urinary tract calculi. Data of patients with urinary tract infection and urolithiasis were retrospectively reviewed to collect information on age, gender, stone size, location, hydronephrosis, procedure of stone removal and antibiotic treatment, identification and susceptibility of pathogens, symptoms, and infectious complications. A total of 912 patients from 11 centers in 7 countries (Bulgaria, Greece, Italy, North Macedonia, Spain, and Turkey) were studied. Mean age was 54 ± 16 years and M/F ratio 322/590. Out of 946 microbial isolates, the most common were E. coli, Gram-positive, KES group (Klebsiella, Enterobacter, Serratia), Proteus spp., and P. aeruginosa. Carbapenems, piperacillin/tazobactam and amikacin showed low resistance rates to E. coli (2.5%, 7%, and 3.6%) and Proteus spp. (7.7%, 16%, and 7.4%), but higher rates were observed with Klebsiella spp., P. aeruginosa, and Gram-positive. Fosfomycin had resistance rates less than 10% to E. coli, 23% to KES group, and 19% to Gram-positive. Amoxicillin/clavulanate, cephalosporins, quinolones, and TMP/SMX showed high resistance rates to most bacterial strains. High rates of antibiotic resistance were observed in patients candidate to stone treatment from South-Eastern Europe. The empirical use of antibiotics with low resistance rates should be reserved to the most serious cases to avoid the increase of multidrug resistant bacteria. Basing on our results, carbapenems, piperacillin/tazobactam, and amikacin may be a possible option for empiric treatment of urinary stone patients showing systemic symptoms.

Detection of TMPRSS2-ERG Fusion Transcript in Biopsy Specimen of Prostate Cancer Patients: A Single Centre Experience.

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. RESULTS: TMPRSS2-ERG fusion transcript was detected in 20 out of 62 (32.2%) patients with prostate carcinoma and among no patients with benign changes whatsoever. There were no significant differences between patients with/without detected TMPRSS2-ERG fusion related to Gleason score. Among 50%, in the study group this score was greater than 7 per/for Median IQR=7 (6-8). Significant difference was recognized, related to the average value of PSA in favour of significantly higher value of PSA in the study group with prostate cancer, but there was also no significant difference between samples with prostate cancer who were with/without detected TMPRSS2-ERG fusion transcript related to PSA level. DISCUSSION: The results from this research are in accordance with the values and results from analyses done in several research centres and oncological institutes. CONCLUSION: The positive findings in small scale studies encourage the implementation of larger scale studies that will be enriched with results of genetic transcript in blood and urine and will define the positive diagnostic meaning of the TMPRSS-ERG fusion transcript.

Comparative Proteomics Analysis of Urine Reveals Down-Regulation of Acute Phase Response Signaling and LXR/RXR Activation Pathways in Prostate Cancer.

Detecting prostate cancer (PCa) using non-invasive diagnostic markers still remains a challenge. The aim of this study was the identification of urine proteins that are sufficiently sensitive and specific to detect PCa in the early stages. Comparative proteomics profiling of urine from patients with PCa, benign prostate hyperplasia, bladder cancer, and renal cancer, coupled with bioinformatics analysis, were performed. Statistically significant difference in abundance showed 20 and 85 proteins in the 2-D DIGE/MS and label-free LC-MS/MS experiments, respectively. In silico analysis indicated activation, binding, and cell movement of subset of immune cells as the top affected cellular functions in PCa, together with the down-regulation of Acute Phase Response Signaling and Liver X Receptor/ Retinoid X Receptor (LXR/RXR) activation pathways. The most promising biomarkers were 35, altered in PCa when compared to more than one group. Half of these have confirmed localization in normal or PCa tissues. Twenty proteins (CD14, AHSG, ENO1, ANXA1, CLU, COL6A1, C3, FGA, FGG, HPX, PTGDS, S100A9, LMAN2, ITIH4, ACTA2, GRN, HBB, PEBP1, CTSB, SPP1) are oncogenes, tumor suppressors, and multifunctional proteins with highly confirmed involvement in PCa, while 9 (AZU1, IGHG1, RNASE2, PZP, REG1A, AMY1A, AMY2A, ACTG2, COL18A1) have been associated with different cancers, but not with PCa so far, and may represent novel findings. LC-MS/MS data are available via ProteomeXchange with identifier PXD008407.

Effects of Serenoa repens Alcohol Extract on Benign Prostate Hyperplasia.

An increasing tendency has recently emerged for the use of phytotherapeutic agents as alternative to commercial pharmacological agents for the treatment of benign prostate hyperplasia (BPH). The purpose of this study is to evaluate the effects of Serenoa repens alcohol extract treatment on BPH patients' symptoms and major parameters during one-year follow-up. The study was performed on 70 men aged 40 - 79 years (mean 60.58) with symptomatic BPH that were divided into a group of 40 patients treated with Serenoa repens extract (SRT) and a control group of 30 patients that received no treatment and were observed only. The following parameters were determined at the time of diagnosis (baseline), and after 6 and 12 months: prostate size, serum prostate-specific antigen (PSA) and uroflowmetry parameters including maximum flow rate (MFR), average flow rate (AFR) and post-voiding residual volume (PVRV). In addition, the relevant patient symptoms were evaluated using the International Prostate Symptom Score (IPSS) system. The patients in the SRT group showed a statistically significant increment of the average MFR and AFR values and reduction of PV relative to the control group (p<0.05). The significant differences between the proportion of patients with prostate volume >40 ml in the SRE treated group vs. control group was observed (p<0.05). The mean IPSS score was highly significantly reduced in the SRT group (p<0.01). The mild improvements of the urine flow, prostate size and IPSS score during 12 months treatment with the Serenoa repens extract indicate possible efficiency of this phytotherapeutic agent in patients with BPH.

Epidemiologic study of urolithiasis in seven countries of South-Eastern Europe: S.E.G.U.R. 1 study.

OBJECTIVE: To investigate some epidemiological aspects of kidney stones in the South- Eastern European area. MATERIALS AND METHODS: From September 2015 to December 2015, 538 consecutive patients were treated and evaluated for reno-ureteral stones in eight departments in Bulgaria, Greece, Italy, FYR Macedonia, Romania, Serbia and Turkey. RESULTS: The age of onset was lower in Turkey and higher in Italy. The rate of recurrent patients was higher in Romania and Serbia, while first renal stone formers were more frequent in Italy. The previous history of kidney stones, the characteristics of the stones and the dietary habits of the patients were different in different countries. In Bulgaria, Greece and Romania larger calculi from recurrent patients were more frequent. In Italy and Turkey smaller calculi from first renal stone formers were more frequent. CONCLUSIONS: The previous history of kidney stones, the characteristics of the stones and the dietary habits of the patients were different in different countries. A common dietary pattern associated with the formation of kidney stones was not observed, but each country showed different risk factors.

Successful Kidney Transplantation in a Patient with Multiple Perioperative Renal Transplant Complications. Case Report.

Kidney transplantations have become common surgical procedures that are associated with high success rates. Nevertheless, the detection, accurate diagnosis and timely management of the perioperative surgical complications sometimes require multidisciplinary team approach for some of the complications may result in significant morbidity, risk of graft loss and/or mortality of the recipient. A case of a 24-year old male patient that developed a number of different surgical complications is reported. The complications included venous graft thrombosis, urinary fistula, wound infection, wound dehiscence and a completely exteriorized transplanted kidney. Despite the various complications and, accordingly, a couple of revisions, finally the patient was discharged with a regular kidney function.

Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer.

BACKGROUND: The key to a more effective diagnosis, prognosis, and therapeutic management of prostate cancer (PCa) could lie in the direct analysis of cancer tissue. In this study, by comparative proteomics analysis of PCa and benign prostate hyperplasia (BPH) tissues we attempted to elucidate the proteins and regulatory pathways involved in this disease. METHODS: The samples used in this study were fresh surgical tissues with clinically and histologically confirmed PCa (n = 19) and BPH (n = 33). We used two dimensional difference in gel electrophoresis (2D DIGE) coupled with mass spectrometry (MS) and bioinformatics analysis. RESULTS: Thirty-nine spots with statistically significant 1.8-fold variation or more in abundance, corresponding to 28 proteins were identified. The IPA analysis pointed out to 3 possible networks regulated within MAPK, ERK, TGFB1, and ubiquitin pathways. Thirteen of the identified proteins, namely, constituents of the intermediate filaments (KRT8, KRT18, DES), potential tumor suppressors (ARHGAP1, AZGP1, GSTM2, and MFAP4), transport and membrane organization proteins (FABP5, GC, and EHD2), chaperons (FKBP4 and HSPD1) and known cancer marker (NME1) have been associated with prostate and other cancers by numerous proteomics, genomics or functional studies. We evidenced for the first time the dysregulation of 9 proteins (CSNK1A1, ARID5B, LYPLA1, PSMB6, RABEP1, TALDO1, UBE2N, PPP1CB, and SERPINB1) that may have role in PCa. The UBE2N, PSMB6, and PPP1CB, involved in cell cycle regulation and progression were evaluated by Western blot analysis which confirmed significantly higher abundances of UBE2N and PSMB6 and significantly lower abundance of PPP1CB in PCa. CONCLUSION: In addition to the identification of substantial number of proteins with known association with PCa, the proteomic approach in this study revealed proteins not previously clearly related to PCa, providing a starting point for further elucidation of their function in disease initiation and progression.

Laparoscopic Adrenalectomy: First Single-Center Experience in the Balkans.

INTRODUCTION: Laparoscopic adrenalectomy has become the preferred approach for removal of the adrenal gland for the management of benign or malignant functioning or nonfunctioning adrenal masses. We aimed to present our initial experience with this procedure. In addition, we compare the clinical outcomes of laparoscopic (LA) vs. the open adrenalectomies (OA) performed at our institutions. Also we report a case of successful laparoscopic treatment of splenic artery aneurism involving laparoscopic splenectomy. PATIENTS AND METHODS: A retrospective analysis of the data of all patients who underwent adrenalectomy at three institutions, over the last 12-year period, since the laparoscopic adrenal surgery was introduced in our country. All patients were assessed regarding the demographic data, hormonal status, operative time, estimated blood loss, complications, size of the tumor, number of patients requiring blood transfusion, hospital stay and conversion to open surgery for LA. RESULTS: Thirty five consecutive patients, aged from 33 to 67 (average age 54 years) underwent unilateral LA adrenalectomy during the study period including 14 right and 21 left sided. The laparoscopic procedure was successfully completed in all except 4 cases, which were converted to open surgery to control bleeding from the avulsed adrenal veins. LA proved superior to OA, resulting in less estimated blood loss, shorter operating time, shorter time to resumption of oral intake, shorter postoperative hospital stay and less analgesic requirements. During the follow-up of 3 to 36 months no tumor recurrence and/or metastasis developed. CONCLUSIONS: Our results concur with other retrospective reviews comparing laparoscopic and open adrenalectomy, demonstrating unequivocal advantages in terms of reduced length of hospital stay, blood loss, return of bowel function, functional recovery and post-operative morbidity.

Insulin Resistance, Glycemia and Cortisol Levels in Surgical Patients who Had Preoperative Caloric Load with Amino Acids.

INTRODUCTION: Surgical stress response, results in elevated levels of anti-insulin hormones and reduced insulin secretion. This hormonal state may be detrimental for surgical patients due to the presence of insulin resistance and hyperglycemia. Additionally, pre-operative fasting favors this conditions. The aim of this study is to analyze the impact of pre-operative caloric load, with 440kJ from amino acid infusions on the levels of glucose, cortisol and insulin resistance in surgical patients. MATERIAL AND METHODS: The study included 20 female patients scheduled for mastectomy, aged 30-60 years without diabetes and BMI < 30 m(2), divided into two groups. The study group A, the evening before the surgery, received 1000 ml amino acid infusions, while the control group B didn't receive any infusion. In both groups glucose, C-peptide and cortisol levels were determinate preoperatively and postoperatively. From the obtained C-peptide and glucose values, with the help of computer model (HOMA2*), the insulin resistance (IR), functionality of beta cells (BETA) and insulin sensitivity (IS) were calculated. RESULTS: Postoperative values of insulin resistance (0.94 ± 0.12 vs 1.13 ± 0.2; p = 0.02) and glucose (4.79 ± 0.5 vs 5.77 ± 0.6; p = 0.002) were lower in the study group compared to control group. Postoperative cortisol levels in both groups were higher than the preoperative, but no significant difference was found. The study group showed higher values for BETA and IS. Percentage changes between the groups were significant for all parameters. CONCLUSION: Pre-operative caloric load (amino acids) reduces the level of insulin resistance and glucose in the presence of elevated cortisol levels.

Mapping and Identification of the Urine Proteome of Prostate Cancer Patients by 2D PAGE/MS.

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 associations between 11 proteins was Cell Death and Survival, Cell-To-Cell Signaling and Interaction, and System Development and Function (p = 10(-30)). In summary, we have created an initial proteomic map of PCa patient's urine. The results from this study provide some leads to understand the molecular bases of prostate cancer.

Incidence of urinary tract tumours in a two-year period (2010-2011) at the Institute of Pathology, Faculty of Medicine, Skopje, Macedonia.

We performed a retrospective analysis of tumours of the kidneys and the lower urinary tract diagnosed at the Institute of Pathology, Faculty of Medicine, Ss. Cyril and Methodius University, Skopje, Macedonia, in a two-year period (2010-2011), with the aim of highlighting the main morphological characteristics and to present the statistical features of these tumours. All the cases were diagnosed on paraffin sections from surgical specimens routinely stained with H&E, and immunohistochemically with a panel of monoclonal antibodies. The analysis revealed a total of 755 cases, of which 166 (14%) were located in the kidney including the renal pelvis, and 649 (86%) were tumours of the urinary bladder. Twelve of the renal tumours (11.3%) were benign, and the rest were malignant tumours. Most of them were adenocarcinomas (n=77; 72.6%) and 17 cases (16%) were transitional cell carcinomas originating from the renal pelvis. The analysis of the lower urinary tract tumours showed a strong prevalence of malignant urothelial tumours (96%), with a male to female ratio of almost 4:1. Low grade morphology was a predominant feature (71.7%) and 51 cases (22.9%) were of high grade. The percentage of urothelial tumours of the kidney in our series is higher than in most of the reported series, which should lead to an expanded analysis.

Can an increased nitric oxide level be accepted as non-invasive marker for sub/acute rejection of the kidney allograft?

BACKGROUND: Subclinical and acute rejections (SAR/AR) continue to have a negative impact on graft survival. The aim of our study was to analyze allograft rejection and nitric oxide (NO) levels in patients with protocol- and clinically-indicated biopsies in relationship with other causes of allograft dysfunction, and to evaluate the clinical impact of NO measurement as non-invasive marker for early diagnosis of SAR/AR. METHODS: In 45 living-related kidney transplants, serum NO levels were measured at: 20 min after reperfusion (NO1); on days 1 (NO2), 5 (NO3), and 14 (NO4); and at the first (NO5) and sixth (NO6) months after transplantation (Tx). Protocol biopsies (Bx) were performed at the first and sixth months after Tx. RESULTS: 38 (42.2%) Bx showed histological features of (SAR), 4 (4.5%) Bx showed mild tubulointerstitial rejection, while 48 (53.3%) Bx had no histological signs of SAR/AR. Significantly higher (NO3) levels were found in patients with AR and (NO5)/(NO6) in SAR as compared to other causes of allograft dysfunction occurred within the first posttransplant month (delayed graft function, urinary tract infection, and cyclosporine toxicity). Sensitivity/specificity for cut-off NO level of 70 µmol/l were 69.2% and 88.4% in AR, and 78.9% and 75.4% for the level of 50 µmol/l in SAR patients, respectively. CONCLUSIONS: Our study reports significantly higher serum NO levels at day 5 and a gradual decrease at day 14 (prior to and at the time of clinically manifested AR), and at 1- and 6-month protocol biopsies in SAR patients as compared to all other causes of renal dysfunction. NO measurement may have a satisfactorily diagnostic performance as a useful non-invasive marker not only for AR, but also for SAR patients.