Prevalence of Y chromosome microdeletions in infertile men with severe oligozoospermia in Serbia.

AIM: The aim of this study was to determine the prevalence and type of microdeletions of the Y chromosome of men with severe oligozoospermia-ICSI candidates in the Serbian population and to compare our findings with those from other parts of the world. METHODS: In all patients spermiogram has been performed in order to determine the sperm concentration. Patients were subjected to detailed clinical, endocrinological and cytogenetic examinations. Microdeletion analysis was performed by polymerase chain reaction (PCR) on 203 patients with normal cytogenetic findings. The STS markers tested in each case were sY84, sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc). RESULTS: at least one of the STS markers was deleted in 11 of the 203 cases (5.4%). CONCLUSION: AZFc microdeletions were identified with a rather high prevalence in men with severe oligozoospermia ICSI candidates in Serbian population.

Molecular analysis of Y chromosome microdeletions in idiopathic cases of male infertility in Serbia.

The aim of this study was to detect frequency of microdeletions of Y chromosome in idiopathic cases of male infertility in Serbian population. Patients were subjected to detailed clinical, endocrinological and cytogenetic examinations. Ninety patients with normal cytogenetic findings with azoospermia and severe oligozoospermia were included in the study. In these patients microdeletion analysis was performed by multiplex polymerase chain reaction (PCR) method on DNA extracted from peripheral blood. In each case 6 markers in azoospermia factor (AZF) regions were tested: sY84, sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc). Deletions on Y chromosome were detected in 14 of 90 cases (15.6%), 9 with azoospermia and 5 with severe oligozoospermia. Of total number of 17 deletions, 11 (64.7%) were detected in AZFc region, 3 (17.6%) in AZFa region and 3 (17.6%) in AZFb region. Microdeletions in AZF region of Y chromosome, especially AZFc microdeletions, represent common genetic cause of idiopathic azoospermia and severe oligozoospremia in Serbian infertile men. Therefore, testing for Y chromosome microdeletions should be considered as an important element in diagnosis and genetic counseling of infertile men in Serbia and decisions regarding the assisted reproduction should be made based on the presence and type of AZF microdeletions.

Genetic variation in leptin and leptin receptor genes as a risk factor for idiopathic male infertility.

The aim of this study was to examine whether there is an association among genetic variability in leptin (LEP) and leptin receptor (LEPR) genes and male infertility. We performed a case-control study and were searching for an association between polymorphisms of LEP and LEPR genes and male infertility. The study group consisted of 317 patients with idiopathic infertility and a control group of 241 fertile men from Slovenia. Four single nucleotide polymorphisms (SNPs) in LEP gene and four single nucleotide polymorphisms (SNPs) in LEPR gene were chosen and genotyped. Statistically significant SNP was further validated in additional 255 infertile patients and 168 controls from Serbia and Macedonia. In the Slovenian population, we found a statistically significant difference in genotype distribution for rs10244329 polymorphism in LEP gene (recessive genotype model, p value = 0.048). The trend toward statistically significant difference in genotype distribution for rs10244329 polymorphism was confirmed in the Serbian and Macedonian populations (p value = 0.07). Our data suggest that genetic variability in the LEP gene might be associated with male infertility warranting further confirmation and mechanistic investigations.

Detection of gastrointestinal and abdominal infections by 99mTc-ciprofloxacin.

BACKGROUND/AIMS: The aim of the study is detection and evaluation of the abdominal and gastrointestinal infective foci using 99mTc-ciprofloxacin (Laboratory for radioactive isotopes, Vinca). METHODOLOGY: In total 21 patients with clinical suspicion on abdominal or gastrointestinal infection were investigated. In all the patients, planar liver/spleen scintigraphy was performed. Ciprofloxacin chloride (3.5 mg) was mixed with 555 MBq of 99mTc in 3 mL of physiological solution and incubated for 20 min. After slow i.v. injection in a cubital vein, dynamic acquisition (1 f/min) was performed during the first 60 min in the position of interest, followed by static acquisition (500,000 imp) anterior and posterior view, abdomen and pelvis after 1 h and 4 h in all patients. When necessary, additional scintigrams were acquired after 24 h. In all the patients with negative or equivocal findings of planar scintigraphy, emission computerized tomography (SPECT) was performed (60 positions, 6 degrees). Interpretation was made by three independent observers. Additional data were provided using clinical findings, ultrasonography, computed tomography and magnetic resonance imaging, laboratory analyses, and surgical or microbiological confirmation of infection. RESULTS: There were eleven true-positive findings, seven true negative, two were false negative while one was false positive due to intestinal obstruction. Sensitivity was 79%, specificity 91%, positive predictive value 92%, negative predictive value 77%, accuracy 84%. CONCLUSIONS: According to our results, scintigraphy with radiolabeled ciprofloxacin is a useful method for detection and assessment of exact localization of abdominal and gastrointestinal infections.

[Combined hormono-radiotherapy in treatment of locally advanced prostate cancer].

Numerous questions regarding combined hormono-radiotherapy in the treatment of locally advanced prostate cancer still remain open. We present results of combined treatment in 133 our patients with locally advanced prostate cancer. All patients recieved hormonotherapy as neoadjuvant, concomitant with radiotherapy (tumor dose range 65-72 Gy), and adjuvant. In six months follow-up time, complete regression (CR) was noted in 120 patients (90%), partial regression (PR) in 6 (4.5%), stabile disease (SD) in 2 (1.5%) and progression of disease (PD) in 5 patients (4%). In mean follow up time of 17 months (6-77), 13 patients relapsed. Five-year time to progression was 70%. Five-year disease-free interval for CR patients was 70%. At the date of last control CR was noted in 116 patients (87%), PR in 2 patients (2%), SD in 7 patients (5%), and 8 patients (6%) had progressive disease. Second malignancy was noted in 4 patients. Multidisciplinary studies directed towards the optimisation of combined treatment are ongoing. There are no definitive conclusions.

[Recanalization of uretero-intestinal anastomoses].

The authors present their own experience related to application of the metallic stents in treatment of ureteroenteric strictures. Over the period of approximately 3 years, we have implanted them in 27 patients (28 strictures). Due to the unsatisfactory therapeutic effects of the repeated balloon catheter dilatations and catheter prostheses the further course of treatment included placement of the metallic Strecker stents of 4-8 cm in length and 6-8 mm in diameter. Six months after the procedure, 58% of the procedures were assessed as satisfactory. After one year, 12 out of 28 were clinically efficient at long-term. The achieved effects were significantly better in comparison to older generation interventional radiology methods.

Treatment of emergency surgical complications of kidney transplantations.

Surgical complications subsequent to the kidney transplantation are not infrequent and they are characterized by the high percentage of graft loss (596-18% in standard surgical procedures and up to 37% in atypically performed transplantations). The study included 311 transplanted patients (206 (66.2%) living donors and 105 (33.8%) cadaver donors). Surgical complications developing during the immediate posttransplantation period as well as during the late period (after a year and a half) were classified as: I urinary complications; II vascular complications; III other complications. In majority of the cases urinary complications (urinary fistulas, ureteral obstructions, vesico-ureteral reflux) as well as other complications (cholecystopancreatitis and lymphocele) did not necessitate urgent treatment, unlike most of the vascular complications. All the vascular complications (29/311) developed during the immediate postoperative period, except for occurrence of arterial stenoses which ensued later on, while the development of symptoms was rapid. Severity of both symptoms and clinical picture necessitated urgent surgical re-intervention in order to preserve the graft and patient's life. Vascular complications were classified as: true vascular complications, hemorrhages and kidney ruptures in order to distinguish technical and other factors contributing to development of the complications. Onset of the true vascular complications related to the graft and recipient blood vessel changes was evidenced in 20 patients (69%/29 patients) while the incidence of hemorrhages and ruptures was considerably lower (14%/29 patients and 17%/29 patients). As for the true vascular complications, vascular stem thrombosis subsequent to cadaveric transplantations was the most frequent, and transplantectomy was performed in all the cases in absence of any lethal outcomes. Two cases with iliac artery rupture resulted in graft loss subsequent to urgen exploration. In all cases with hemorrhages the applied therapy resulted in positive responses, except in one case in which massive gastrointestinal hemorrhage led to lethal outcome. The response to the urgent surgical treatment of spontaneous kidney graft ruptures was positive in 60% of the cases, while in the remaining 40% transplantectomy was necessitated due to the extensiveness of the lesion in order to preserve patient's life.

[Percutaneous-retrograde recanalization of ureteral stricture with a curved metal stent].

Our own experience in application of a combined percutaneous-retrograde approach for recanalization of the urethral structures in 4 patients in presented. Metallic guide is placed via the previously created percutaneous nephrostomy while dilatation or insertion of the metallic stent is performed retrogradely. The approach is used in the strictures in which percutaneou's placement of the recanalization balloon catheter into the stricture site was impossible. The method was successfully applied in all 4 cases in absence of any complications.

[Recanalization of urethral strictures using a temporary curved biocompatible new generation metal endoprosthesis]].

The male urethral stricture treatment is actual clinical issue with its resolution being increasingly frequently based on application of minimum invasive therapeutic interventional uroradiology methods. Since the methodology is applied over the last two decades, the most reasonable therapeutic algorithm has not been defined yet with respect to the correlation with the contemporary surgical treatment. The results of application of the temporary covered self-expandable nitinol Allium stents, which have been applied for the first time ever at our Institution in October 2003. Over the last 3 years, the method was applied in 40 males, averagely aged 54 years with urethral strictures previously treated by urological methods. In four cases, stent placement was performed after endourethral incision. The most common etiology of the stricture was the posttraumatic (55%), post-inflammatory (32%) and iatrogenic (10%). In all the cases, stents were removed 12-14 months after their insertions. The results are evaluated using uroflowmetry and urethrocystography, revealing in 85% of the cases permanent recanalization free of dysuric complaints. Development of a stricture on the anterior stent end was evidenced in 15% of the cases.

Results of application of orthotopic urine diversion according to Studer.

INTRODUCTION: Prolonged survival of patients undergoing radical cystectomy due to the infiltrative carcinoma of the urinary bladder has increased the need for development of the orthotopic bladder enabling preservation of the upper urinary ways for the extended period of time. Orthotopic bladder with tubular afferent segments in which ureters are implanted without antireflux mechanism has been introduced into the practice in 1984 by Studer and collaborates. MATERIAL AND METHODS: In the period 1998-2007 12 patients averagely aged 62 years were subjected to orthotopic derivation from ileum, when low-pressure reservoir was constructed and the ureters were implanted into the afferent non detubularized segment of ileum without antireflux mechanism. The follow-ups included determination of serum creatinine level, ultrasound monitoring of the upper urinary ways condition in three-month intervals and pyeloureterography with intravenously applied contrast medium one year after the surgery. Immediately before the follow-up examinations, the patients were asked to complete voiding and incontinence onset diary. RESULTS: Complete exclusion of the kidney that was in the stasis before surgery was evidenced only in one case, in a patient with tumor infiltration of the ureteral orifice. Significant obstruction of the uretero-ileal anastomosis was found in 4 renal units and it was resolved by antegrade balloon catheter dilatation. Diurnal continence was established in all patients within the initial 6 months after the surgery. Mild form of nocturnal incontinence persisted in 33% of the patients. Stenosis of the urethrovesical anastomosis was a cause of urine retention in 1.8% of patients and it was endoscopically resolved. CONCLUSION: The advantage of implantation into the afferent non detubularized segment of ileum over the antireflux mechanism has been verified in our study based on the low percent of stenoses.

Elevated plasma D-dimer as a predictor of postoperative complications after radical cystectomy.

Detailed preoperative evaluation is essential in prevention of perioperative complications. As thorough anamnesis, physical examination and standard laboratory investigation do not contribute much in prediction of perioperative complications and outcome, and detection of tumor markers is also insufficient in means of prognosis, some molecular marker have emerged lately as prognostic markers in surgery. Recent data on pathophysiological processes stress response, derangements of hemostasis, in sepsis or in thromboembolism as well as in malignancy, indicate that presence or elevation of some molecular markers of fibrinolysis can indicate possibility of perioperative complications and even predict outcome. As it is evident that neoplastic cells enhance thrombin and other procoagulant production, detection of degree of activation of coagulation and fibrinolysis can contribute in prediction of treatment outcome in patients with bladder carcinoma scheduled for radical surgical procedures.

Chemotherapy by M-VAC protocol in progressive bladder carcinoma treatment.

Treatment of invasive bladder carcinoma is complex therapy procedure which means surgical and non-surgical treatment appliance. In spite of radical surgical treatment conduction, the gold standard in invasive bladder tumor therapy, about 30-40% patients spread metastasis in further disease course. The system chemotherapy in invasive bladder tumors treatments is marked with accent. Its fundamental aim is to correct results of surgical treatment. This therapy option very often means the only modality in bladder carcinoma treatment, for instance, in the diseminal disease faze. The adjuvant chemotherapy imposes a task to correct surgical treatments results in case where the high risk of recidive breaking out exists. As risks for recidive breaking out cite are: a) lymphatic and vascular invasion into the primary tumor; b) extravezical tumor extension-T3b; c) tumor invasion neighboring structures-T4; d) positive lgl findings-N+. After radical cystectomy caused by high level malignancy tumors - T3b,T4, is founded frequency of positive IgI of about 40-60%. Patients with positive lgl have badly prognosis. Only 17% they survive longer than two years, and 7% have surviving of five years.

[Morphologic characteristics of the urothelial bladder tumors]. / Morfoloske karakteristike tumora urotelijuma mokracne besike.

Cancer of the urinary bladder is the fourth most common cancer in men and the ninth in women. Approximately 67,000 people (50,000 males and 17,000 females) develop bladder cancer each year in the United States, and 13,750 individuals (9,630 males and 4,120 females) are expected to die from it. In the showing of the morphologic characteristics of the tumors, authors underlining the increasing of the incidence, pathogenesis, premalignant lesions and the risk factors of disease.

Modified Mainz pouch II urinary diversion and quality of life.

The current referential literature describes over 40 surgical techniques of continent urinary derivations. A variation of ureterosigmoidostomy, published by Hadzi Djokic et al. (1996) is a combination of the original Mainz pouch II (sigma rectum pouch) technique (Fish & Hohenfellner, 1991) and modified ureterointestinal anastomosis as described by Camey & LeDuc (1979) with a few new details described by the author himself. In the period 1994-2006, the total of 236 patients were treated by this method. Radical cystectomy in cases of multifocal transitional cell carcinoma of the bladder was the most common indication for this method (91,5%). In the course of follow-up (mean duration 24 months) the quality of life (QL) of these patients was evaluated by physical characteristics, mental status, social aspects and comparative evaluation of quality of life with ileal conduit which is still considered the "gold standard" for urinary derivations. A very good quality of life in all studied dimensions (3/4) patients) suggests the fact that this form of continent urinary derivation provides the patients with the fair quality of life and confirms justifiability of this surgical procedure under certain indications.

Determination of biochemical relapse after radical prostatectomy by biological detection limit (BDL) after cystoprostatectomy using two PSA assays.

The monitoring of PSA values following prostatectomy demands for the use of highly sensitive tests with low detection level. The possibilities to use the EIA Dialab test to monitor the PSA values after radical prostatectomy for early detection of persistent diseases were investigated by determining the biological detection limit (BDL) in serum of patients who unrewent cystoprostatectomy. The obtained values were compared with Abbott Imx test for PSA determination. A good correlation between the two studied methods was establisahed, r = 0.9827 with the regression curve Yx = 0.20463 + 0.96277. Test indicated that there was no significant difference (p < 0.001) between the investigated methods.

Radical radiotherapy for localized prostate cancer in elderly.

BACKGROUND: Prostate cancer is an age related neoplasm, with high incidence in the group of elderly man. The correct management must to be balanced between the benefits of the treatment and its disadvantages. Radiotherapy as definitive treatment is commonly reserved for older patients and patients with high surgical risk and is widely used as a treatment of choice. AIM: The aim of this study was to determine the role of radical radiotherapy for localized prostate carcinoma in patients 70 years age or older concerning treatment morbidity, local control, disease free and overall survival. MATERIAL AND METHODS: A clinical prospective non-randomized study was performed including 103 elderly patients with an age 70 or above, between January 1991 and April 2005, at the Institute for Oncology and Radiology of Serbia. Median age of patients was 74,89 years (range 70- 80 years). Stage distribution was as follows: stage A--3 patients (2.9%), stage B--69 patients (67%) and stage C--31 patients (30.1%). Out of 103 patients, initial PSA value was noted in 87 patients. The mean value of initial PSA was 18,06 ng/ml. Radical radiotherapy was conducted on megavoltage linear accelerators with high energy photons (10, 18 MeV) and total tumor dose of 65 Gy. RESULTS: Low grade acute complications were registered in 70 patients (65%). Mean follow up time was 40, 13 months. The disease outcome at the last follow up show that 79 patients (76.7%) had no evidence of disease and 24 patients (23.3%) relapsed. Overall survival rates were 65, 29% and 44, 52% and disease free survival 66, 59% and 63, 26% at 5 and 10 years. Disease specific survival was at 5 and 10 years 73,32% and 65, 42% respectively. Late sequelas (gradus I and II) are registered in 22 patients (21.36%), out of 103. CONCLUSION: Radical radiotherapy for localized carcinoma of the prostate is effective treatment option in elderly patients with good local control, present treatment tolerance providing good quality of life and long-term cure.

Histopathological evaluation of radical prostatectomy in the treatment of localized prostate cancer.

Incidence of prostate cancer has risen dramatically in the past decade. Radical prostatectomy is indicated in patients who have disease localized to the prostate. The aim of the study is to make histopathological evaluation of radical prostatectomy in the treatment local prostate cancer. Authors analyzed 49 cases of radical prostatectomy due to cancer localized to the prostate in period 1996-2000 in Clinic of Urology in Clinical Center of Serbia, Belgrade. The average age of the patients was 65, 6 years (range 44-76, pick 61-70). The most cases 25 (51%, p < 0.001) we found in pT2a N0M0, in pT2b N1M0 9 (18.36%), in pT3bN0M0 10 (20.4%), in pT3bN1M0 3 (6.12%), in pT4aN0M0 2 (4.08%). Nodal status positive was in 12 cases: 9 (18%) in pT2bN1M0- iliac 3 (right 2, left 1), obturatory 6 (right 1, left 5) and 3 cases in pT3bN1M0-iliac left 1 and obturatory 2 (1 right and 1 left). We found Gleason score 8 in 9 cases (18.36%) in pT2bN1M0 versus 7 cases (14.5%) without nodal metastases. Gleason score 9 we found in 3 cases (6.1%) in pT3bN1M0 versus one case without nodal metastases (difference is not significant). Gleason score 3 was in 6.1%, 4 in 12.2%, 5 in 8.1%, 6 in 16, 3%, 7 in 24.5%. Grade 1 of tumors we found in 9 cases (18%), grade 2 in 11 (22%), grade 3 in 29 (60%). HG PIN was in 18 cases (36.7%), LG PIN in 10 (20.4%). In all cases was elevated PSA: 4-10 mmol/L in 24 pts, 11-20 in 15 pts and > 20 in 10 pts. Radical prostatectomy is most adequate method in surgical treatment cancer localized in the prostate. Pelvic lymphadenectomy is necessary for staging purposes in adenocarcinoma of the prostate. Early detection adenocarcinoma of the prostate is important factor in decreasing rate of death.

Anesthesia for radical prostatectomy.

Radical prostatectomy is one of most common treatment options currently recommended for clinically localized prostate cancer. Evaluation of intraoperative and postoperative complications is important in evaluation of relative morbidity of this treatment option. Furthermore, investigation of complications of surgical treatment in correlation with not only surgical technique, but comorbidity, ASA stage and anesthetic technique enables improvements in complete perioperative treatment and decrease of incidence of complications resulting from the procedure. Improvement of anesthetic techniques and use of new anesthetic agents contributes to better outcome of surgical treatment. For radical surgery, combined epidural analgesia and general anesthesia reduces postoperative complications and mortality. Benefits can be conferred most likely by altered coagulation activation in surgery, increased blood flow, reduction of operative stress response. Modalities for reduction of intraoperative blood loss during radical prostatectomy are normovolemic haemodilution, preoperative donation of blood for autologus transfusion and use of erythropoietin for increasing red cell mass.

Standardization of transrectal ultrasound-guided biopsy.

Ultrasound-guided biopsy is more sensitive to biopsy performed under the digital control, because 29% of prostatic cancers are not palpable. On the other hand, at least 30% of cancers are isoechogenic, so they cannot be viewed by transrectal ultrasound examination. It means that target biopsy is not sufficient for diagnosis of localized prostatic cancer, i.e., randomized samples are needed as well. More than ten years ago, the technique of sampling the six specimens became a standard procedure to which previously harvested target specimens from suspected growths were added. Today, the expansion of biopsy protocol is recommended, by obtaining the additional specimens from peripheral lateral area, four plus two samples if the prostate has volume over 50 ml. Larger number of biopsies requires anesthesia. In order to reduce complication, the cleaning of rectal ampulla and prophylactic use of quinolone are suggested.

The possibilities of age reference values of PSA density in prostatic cancer screening.

INTRODUCTION: The possibilities of PSA (prostate specific antigen) test in screening of prostatic cancer may be evaluated by measuring its sensitivity, specificity and positive predictive value. The majority of reference articles in this field has evaluated the possibility of detection of prostatic cancer by radioimmunoassay (RIA). MATERIAL AND METHODS: Prospective study included 2000 male patients over 50 years of age. The objective of the study was to examine the possibility of enzyme PSA test for differentiation of benign prostatic hyperplasia (BPH) and localized prostatic cancer (PC). The possibility of enzyme PSA assay for detection of prostatic cancer was compared with RIA method, by digital rectal examination and echotomography. The effect of PSA density and age reference values for differentiation of PC from BPH was also examined. DISCUSSION: The results of enzyme immunoassay test (EIA) were compatible with radioimmunoassay results (RIA). Diagnostic algorithm of prostatic cancer detection should be corrected with PSA density values according to aged-specific groups (49 years - 0.09 ng/ml/cm3; 59 years - 0.13 ng/ml/cm3; 69 years - 0.17 ng/ml/cm3; 79 years - 0.19 ng/ml/cm3) in order to reduce the number of false positive results in PSAD grey zone (0.10 - 0.20).