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.

Proteomics Profiling of Bladder Cancer Tissues from Early to Advanced Stages Reveals NNMT and GALK1 as Biomarkers for Early Detection and Prognosis of BCa.

The high recurrence rate and invasive diagnostic and monitoring methods in bladder cancer (BCa) clinical management require the development of new non-invasive molecular tools for early detection, particularly for low-grade and low-stage BCa as well as for risk stratification. By using an in-solution digestion method and label-free data-independent LC-MS/MS coupled with ion mobility, we profiled the BCa tissues from initiation to advanced stages and confidently identified and quantified 1619 proteins (≥2 peptides). A statistically significant difference in abundance (Anova ≤ 0.05) showed 494 proteins. Significant correlation with stage with steady up or down with BCa stages showed 15 proteins. Testing of NNMT, GALK1, and HTRA1 in urine samples showed excellent diagnostic potential for NNMT and GALK1 with AUC of 1.000 (95% CI: 1.000-1.000; p < 0.0001) and 0.801 (95% CI: 0.655-0.947; p < 0.0001), respectively. NNMT and GALK1 also showed very good potential in discriminating non-invasive low-grade from invasive high-grade BCa with AUC of 0.763 (95% CI: 0.606-0.921; p = 0.001) and 0.801 (95% CI: 0.653-0.950; p < 0.0001), respectively. The combination of NNMT and GALK1 increased prognostic accuracy (AUC = 0.813). Our results broaden the range of potential novel candidates for non-invasive BCa diagnosis and prognosis.

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.

Penile cancer after a tick bite: A possible association.

Penile cancer is a rare cancer in Western countries, but is more common in parts of the developing world. Usually, it is associated with older uncircumcised men who have a long-term phymotic preputium. Here, we report a case of penile cancer in a circumcised patient, occurring 3 months after a tick bite on the head of the penis. To the best of our knowledge, this is the first report that suggests a possible association between Lyme disease and occurrence of "de novo" penile cancer. Further studies are needed to confirm this hypothesis.

Effect of bladder cancer variant histology on survival outcome in patients treated with radical cystectomy: A single-centre experience.

CONTEXT: Bladder cancer (BC) is the sixth most common malignant neoplasm in men. Recently, great effort has been devoted to the study of BC variant histology (VH). Yet, the results from these studies have shown conflicting data and remain unclear whether their presence alters recurrence and survival rates after radical cystectomy (RC). AIMS: We undertook this study aiming to test the effect on VH on recurrence-free survival (RFS) and overall survival (OS) in single-center RC patients. SETTINGS AND DESIGN: We have retrospectively analyzed medical records and pathology reports from 331 patients who underwent RC with or without pelvic lymphadenectomy at University Urology Clinic-Skopje, North Macedonia, in the period between 2010 and 2018. SUBJECTS AND METHODS: Microscopic analysis of the specimens involved the evaluation of histological tumor type, tumor grade, pathological tumor node metastasis stage, presence of lymphovascular invasion, and resection margin status. STATISTICAL ANALYSIS USED: Univariable and multivariable Cox regression models were applied to test the effect of VH on RFS and OS. RESULTS: We found 185 patients who matched our inclusion criteria. At multivariable analyses, lymphovascular invasion and positive resection margins were associated with shorter RFS. Similarly, patients diagnosed with lymphovascular invasion, positive resection margins, and a pelvic lymph node metastasis had poorer OS. VH was not found to be an independent predictor of both RFS and OS (P > 0.05). CONCLUSIONS: The present study did not reveal prognostic effect of VH on RFS and OS. In our series, histomorphologic parameters including lymphovascular invasion, resection margins, and pelvic lymph node metastasis were the most relevant predictors on survival outcome after RC.

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.

Solitary Fibrous Tumor of Adrenal Gland and Review of the Literature.

Solitary fibrous tumor (SFT) is a rare and still controversial entity. This type of tumor first appeared in the literature as a pleural lesion, but, over the last decades, it has been reported in many extrathoracic sites. As a tumor of the adrenal gland, SFT is still rare and very uncommon, thus extensive research among the English language literature has been performed. We present here a case report of an adrenal SFT which is compared to 11 other known cases. Our case report is from a patient with SFT on the left adrenal gland, followed by mild symptoms of abdominal discomfort and hypertension. Physical examination, laboratory, and radiological tests were performed. The patient underwent surgery and the material was sent for histopathologic analysis for a definite diagnosis. Regular follow up appointments were performed over the course of two years. No recurrence of the tumor has been detected. We explain the symptoms, diagnosis, treatment, and additionally we describe the results and implications of the findings reported in the literature. Correct diagnosis is mandatory for optimal management of solitary fibrous tumor patients.

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.

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.

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.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer.

INTRODUCTION: Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). OBJECTIVE: The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients' clinical outcome. MATERIALS AND METHODS: In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. RESULTS: UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. CONCLUSIONS: The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

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.

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.

The improvement in kidney transplant program in R. Macedonia--what are the clues?

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, prerequisites for a deceased donor (DD) programme would be the creation of an official waiting list of candidates for DD transplantation, organizational and infrastructural networking and raising public awareness on the number of potential deceased donors through permanent media presentation. Our involvement in the South-eastern Europe Health Network (SEEHN) initiative and the support from the newly created Regional Health Development Centre (RHDC) on Organ Donation and Transplant Medicine established in Croatia (Zagreb) was shown as successful for improvement of the KTx programme. At the very first professional meeting (27-28 May, 2011 in Skopje, Macedonia), the organ donation and transplantation needs of each country within the SEE geographical region were addressed and action plans for further steps on how to proceed were established. Hence, the number of professionals (including vascular surgeons) involved in KTx was increased along with the substantial increase in the reimbursement per transplant procedure at the Urology Department. Nowadays, we are pleased to report 24 successfully performed LDKTx in 2012, and in 2013 for 7 months 28 transplantations, awaiting 40 KTx at the end of the year. Prospectively, we should initiate the deceased donor programme, even in order to sustain the already established high number of transplantation per month/year, since the potential for LDKTx may be exhausted. We also hope to be supportive for regional collaboration and transplantation of CKD patients from the neighbouring countries (Albania and Kosovo), and eventually to establish regional networking in deceased donor procurement, exchange and allocation practice.

Acute fulminant hepatatis in kidney transplant recipient after repeated sevoflurane anesthesia--a case report and literature review.

INTRODUCTION: A liver dysfunction induced by halogenated volatile anaesthetics is considered as a significant diagnostic problem. The aim of our report was to describe the first case of lethal hepatic failure in a female patient undergoing kidney transplantation (KTx) from a living donor after repeated sevoflurane anaesthesia. CASE PRESENTATION: A 47-year-old hypertensive and diabetic female patient received kidney from her 70-year-old mother. There was an immediate graft function and around 800 ml of blood loss on the abdominal drains, which gradually decreased after the erythrocyte and fresh frozen plasma (FFP) substitution. On the first postoperative (p.o.) day she gradually became anuric and overweighed at the next day undergoing dialysis. Because of prolonged hypotension and somnolence she required reintubation. The second day transaminases increased (AST&ALT>700, LDH>1200 U/L). On the third p.o. day she was urgently reoperated because of a sudden excessive bleeding. However, there was a rather slow flow of tears from the whole operative field that was even more excessive after the operation with signs of a consumptive coagulopathy. She was adequately substituted until the bleeding stopped more than 24 hrs after its onset. The new laboratory results showed further increase in transaminazes (3300 U/L-ALT, 5100-AST, 8900-LDH) and ultrasound investigation confirmed an extensive toxic hepatic lesion. On the fourth p.o. night the patient was stable, diuresis rate was at 100 ml/hour, but in the morning she became hyposaturated because of an increased bronchial secretion. The dialysis could not improve the cardio-respiratory insufficiency and she died 30min later. CONCLUSIONS: This case report suggests that sevoflurane can lead to a severe hepatotoxicity in at-risk individuals with repeated sevoflurane anaesthesia, having renal failure, in those with a preoperative known history of cardiovascular disorders, as well as in those with excessive extracellular volume. A particular precaution should be considered in cases of an elective surgery including organ transplantation.

Penile strangulation: two case reports and review of the literature.

INTRODUCTION: Entrapment or strangulation of the penis is a rare emergency situation that can lead to a wide range of vascular and mechanical injuries. AIM: The aim of this article is to present our experience dealing with penile strangulation. A review of the literature is also summarized in this report. Current treatment options and outcomes are also evaluated. METHODS: We performed a computerized MEDLINE search followed by a manual bibliographic review of cross-references. These reports were analyzed and the important findings summarized. RESULTS: Penile strangulation has been first time reported in 1755. Since that time, sporadic reports have appeared in the literature describing a variety of foreign bodies on the penis that have in common only the property of circularity. We noted motives, types of objects, types of strangulation, symptomatology, trauma grades, diagnoses, including psychological involvement, as well as possible treatment options. Furthermore, two cases of penile strangulation from our clinical practice are presented involving different degrees of vascular insult leading to different pathogenesis, clinical presentation, and surgical approach. CONCLUSION: Penile strangulation is an unusual clinical condition and the consequences can be severe. Penile strangulation could lead to different degrees of vascular obstruction. Consequently, several clinical syndromes can occur: from mild nonsignificant vascular obstruction that resolves after decompression to severe gangrene of the penis accompanied with impaired renal function. The most common motive associated with foreign bodies on the penis is sexual or erotic in nature. The choice of method for removal depends upon type, size, incarceration time, trauma grade, and availability of the equipment. Prompt diagnosis and early treatment are essential to avoid the potential complications of ischemic necrosis and autoamputation.