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These guidelines refer to classification, diagnostics and treatment of prostatitis syndrome. The aim of these guidelines is the standardization, harmonization and optimization of diagnostics, treatment and monitoring of patients with prostatitis that would lead to improved quality of health care for these patients and promote rational use of antibiotics. The guidelines are primarily intended for general practitioners and specialists working in primary health care and hospitals. The members of the Working Group (WG) for the development of guidelines on diagnostics and treatment of prostatitis were appointed by the Croatian Ministry of Health. The evidence for these guidelines was identified by systematic review of the literature, local antibiotic resistance data, existing clinical protocols for diagnostics and treatment of prostatitis, as well as suggestions and comments from colleagues physicians. Through continuing medical education courses, the guidelines were widely presented to family medicine physicians and specialists working in primary health care and hospitals – urologists, infectious disease specialists, microbiologists and nephrologists. The final version of the guidelines was reviewed and approved by members of the Intersectoral Coordination Mechanism for the Control of Antimicrobial Resistance (ISKRA). These guidelines also present clinical instructions aimed at standardizing the procedures and criteria for diagnosis and treatment of patients with prostatitis in Croatia.

Smjernice se odnose na klasifikaciju, dijagnostiku i liječenje sindroma prostatitisa. Njihov su cilj standardizacija, izjednačavanje i optimalizacija dijagnostike, liječenja i praćenja bolesnika s prostatitisom koji će dovesti do poboljšanja kvalitete zdravstvene zaštite ovih bolesnika te promovirati racionalnu potrošnju antibiotika. Namijenjene su ponajprije liječnicima opće prakse i specijalistima koji rade u primarnoj zdravstvenoj zaštiti i bolnicama. Ministarstvo zdravstva Republike Hrvatske (RH) imenovalo je članove Radne grupe za izradu smjernica namijenjenih dijagnostici i liječenju prostatitisa. Smjernice se temelje na dokazima iz sistematski pregledane literature, na lokalnim podacima o osjetljivosti bakterija na antibiotike, na postojećim kliničkim protokolima za dijagnostiku i liječenje prostatitisa, kao i prijedlozima i komentarima kolega liječnika. One su putem tečajeva trajne edukacije široko predstavljene liječnicima obiteljske medicine te specijalistima koji rade u primarnoj zdravstvenoj zaštiti i bolnicama – urolozima, infektolozima, mikrobiolozima i nefrolozima. Završnu verziju smjernica pregledali su i prihvatili članovi Interdisciplinarne sekcije za kontrolu rezistencije na antibiotike. U smjernicama su predstavljene kliničke upute radi standardizacije postupaka i kriterija za postavljanje dijagnoze i liječenje bolesnika s prostatitisom u RH

Diabetes mellitus je jedna od najčešćih kroničnih bolesti u stanovništvu razvijenih zemalja i zemalja u razvoju. Prema podacima Međunarodne federacije za dijabetes (International Diabetes Federation), u svijetu od dijabetesa boluje oko 383 milijuna osoba, a procjenjuje se da bi broj oboljelih do 2035. god. mogao porasti na 592 milijuna (http://www.idf.org/). Prema podacima Hrvatskog zavoda za javno zdravstvo (Izvješće o umrlim osobama u 2013. godini, http://hzjz.hr), u Republici Hrvatskoj dijabetes se nalazi na 8. mjestu među vodećim uzrocima smrti. Godišnje u svijetu umre oko 5 milijuna osoba od posljedica dijabetesa pa ova bolest postaje glavni rastući zdravstveni i ekonomski problem. Trenutačne terapije inzulinom, metforminom ili sulfonilurejom u svrhu smanjenja razine GUK često su nedjelotvorne ili problematične zbog pojave hipoglikemije i povećanja tjelesne mase, a ponekad dovode do smrtnih slučajeva kao posljedice kardiovaskularnih bolesti. Stoga razvoj nove klase lijekova za terapiju dijabetesa, s potpuno novim mehanizmom djelovanja na razini inhibicije ključnih prijenosnika glukoze, predstavlja suvremeni izazov za farmaceutsku industriju i kliničku farmakologiju. Ciljevi takve terapije su proteini iz obitelji SLC5A (Solute carrier, family 5A), odnosno suprijenosnici natrija i glukoze (Sodium-Glucose Cotransporters) tip 1 i 2, tj. SGLT1 (gen SLC5A1) i SGLT2 (gen SLC5A2). Sukladno hipotezi, inhibicija aktivnosti proteina SGLT smanjit će apsorpciju glukoze u tankom crijevu i/ili reapsorpciju glukoze u bubrezima te time povećati ekskreciju glukoze urinom i sniziti GUK (na tašte i poslije obroka). Prema zakonom propisanim uvjetima pri testiranju potencijalnih lijekova, obavezno se provode pretklinička testiranja na najmanje dvije različite vrste pokusnih životinja, najčešće na glodavcima (miševi i štakori), kako bi se odredila farmakodinamika i farmakokinetika lijeka, njegov učinak na metabolizam, reprodukciju i brojne fiziološke parametre te toksikološki učinci. Takvi eksperimenti utvrđuju specifičnost te poželjne i nepoželjne učinke ispitivanog lijeka, a neophodni su za procjenu učinkovitosti djelovanja i sigurnosti za ljudsko zdravlje pri upotrebi. Naši najnoviji podaci za organe u čovjeka (imunokemijska analiza napravljena je specifičnim nekomercijalnim protutijelima) ukazuju da se protein SGLT1 nalazi u luminalnoj membrani enterocita tankog crijeva, četkastoj membrani odsječaka S3 proksimalnih kanalića, luminalnoj membrani žučnih kanala jetre, alveolarnom epitelu (stanice tipa 2) i Clara stanicama bronhiola pluća te u kapilarama srca. Nasuprot širokoj rasprostranjenosti SGLT1/Sglt1, prijenosnik SGLT2/Sglt2 nađen je isključivo u četkastoj membrani proksimalnih kanalića, glavninom u odsječcima S1/S2, u bubrezima miševa, štakora i čovjeka. Novootkrivene lokalizacije proteina SGLT1/Sglt1 u drugim organima, osim u tankom crijevu i bubrezima, ukazuju na neke nove uloge ovoga prijenosnika, koje su od fiziološkog značaja i biomedicinske važnosti. Potencijalni inhibitori SGLT1, koji se testiraju za liječenje dijabetesa, mogli bi, osim u bubrezima i tankom crijevu, inhibirati SGLT1-ovisan transport glukoze i u drugim organima i tako dovesti do bitnih poremećaja funkcije tih organa pa čak i do smrti čovjeka.

Diabetes mellitus, one of the most common chronic diseases in population, is becoming a major health and economic problem. Current therapies with insulin and metformin, aimed at reducing blood glucose, are often ineffective and/or problematic due to the induction of hypoglycemia, body weight gain, and occasional death resulting from cardiovascular disease. A novel generation of oral anti-diabetics inhibits sodium-D-glucose cotransporters in the small intestine (SGLT1/SLC5A1), thus diminishing the absorption of glucose from the diet, as well as in the kidneys(SGLT1 and/or SGLT2/SLC5A2), thus decreasing glucose reabsorption along the nephron and enhancing its excretion through urine. Overall, this improves glycemia, reduces body weight, lowers blood pressure, and decreases damage to the cardiovascular system. However, our recent studies showed that in humans, SGLT1 is not expressed only in the intestinal and renal epithelium ; it was also detected in the liver (bile duct epithelium), lungs (bronchiolar Clara cells and alveolar type II cells), and heart (blood capillaries). These places represent possible targets for novel SGLT1 inhibitors. SGLT1 or dual (SGLT1+SGLT2) inhibitors may inhibit various SGLTs-related functions, such as fluid absorption in the lungs, energy supply to Clara cells, and glucose release from the heart capillaries, and may thus cause functional disorders. In addition, our novel unpublished data showed that in mice, Sglt1 is localized in the kidneys, small intestine, liver, pancreas, salivary glands, tongue, prostate, seminal vesicles, and uterus. The newly discovered localizations of SGLT1/Sglt1 suggest certain novel functions for this transporter, which could be of great physiological and biomedical importance.

In human kidneys, endogenous and exogenous organic anions (OA) are removed by organic anion transporters (OAT) that belong to the SLC family of transporters and reside in the basolateral membrane (BLM) of epithelial cells along the nephron, pedominantly in proximal tubules. The active contributors to this process are the primary-active sodium-potassium adenosine triphosphatase (Na/K-ATPase), secondary-active sodium-dicarboxylate cotransporter 3 (NaDC3/SLC13A3) and tertiary-active OA exchangers OAT1/SLC22A6, OAT2/SLC22A7, and OAT3/SLC22A8. Several previous studies showed that the expression of renal OAT1-3 was sex-dependent in rodents (rats and mice), but similar investigations in human kidneys have not been reported. Accordingly, here we studied the expression and distribution of various BLM transporters that contribute to OA secretion along the human nephron by immunofluorescence cytochemistry (IC) in tissue cryosections and by Western blotting (WB) of total cell membranes (TCM) isolated from the kidneys of men (M ; n = 7 ) and women (W ; n = 9). Virtually healthy kidney tissue was obtained following surgical removal of the carcinoma-diseased organs. Specificity of the used polyclonal antibodies for human NaDC3 and OAT1-3 was confirmed in the transporters-transfected HEK293 cells by IC and WB, whereas the proper transfection was validated in uptake experiments with radiolabeled succinate (NaDC3), p-aminohippurate (OAT1), cGMP (OAT2) and estrone-3-sulfate (OAT3). In IC studies, in human kidneys we confirmed colocalization of Na/K-ATPase, NaDC3 and OAT1-3 in the proximal tubule BLM, whereas Na/K-ATPase and NaDC3 were also colocalized in the BLM of collecting ducts. In WB of TCM, the protein bands of ~85, ~80, ~75 and ~110 kDa were detected for OAT1, OAT2, OAT3 and Na/K-ATPase, respectively, whereas two protein bands of 70 and 90 kDa were detected for NaDC3. The density of protein bands in WB studies, and the staining intensity of various transporters in IC studies were similar in M and W kidneys. Therefore, various primary-, secondary- and tertiary-active transporters that contribute to OA secretion along the human nephron exhibit fair colocalization in the proximal tubules, but in more distal nephron segments, the co-expression is restricted to Na/K-ATPase and NaDC3. Sex differences in the expression of tested transporters were not observed, thus indicating that the sex-dependent expression of some renal transporters is species-related.

The aims of this study were to examine content and expression level of proopiomelanocortin (POMC) mRNA variants in human dermal fibroblasts (HDF) as compared to primary keratinocytes and HaCaT cells of keratinocyte origin. Primary fibroblasts and keratinocytes were obtained from normal human foreskin. Full-length and total (i.e. the full-length, truncated and/or alternatively spliced) POMC mRNA in skin cells were determined by qRT-PCR using specific probes. The full-length POMC mRNA in HDF is neither constitutively expressed, nor could be induced by corticotropin releasing hormone (CRH) or cytokines interferon γ (IFN-γ) and transforming growth factor-β1 (TGF-β1). However, the truncated/alternatively spliced POMC mRNA variants are constitutively expressed in HDF and could be moderately increased with CRH and the cytokines. Primary keratinocytes, in addition to truncated/alternatively spliced POMC mRNA variants, also constitutively express full-length POMC mRNA, both being downregulated during in vitro culturing. Unlike primary keratinocytes, HaCaT cells, express only truncated/alternatively spliced POMC mRNA variants. The level of POMC mRNA expression in HaCaT cells was associated with differentiation stage, being higher in more differentiated cells. Thus, in this study we have shown for the first time that HDF do not express the full-length POMC mRNA, either constitutively or upon activation, opposing to primary keratinocytes which constitutively express the full-length POMC mRNA as a minor variant. Although expressing only truncated/alternatively spliced POMC mRNA variant, HDF express POMC peptide, showing that those transcriptional variants are translatable. Truncated/alternatively spliced POMC mRNA variants, expressed both in HDF and keratinocytes are subjected to regulation, implicating their functionality. Furthermore, the IFN-γ-induced up-regulation at transcriptional level was associated with increased level of POMC peptide detected in HDF lysates. Thus, data of this study have shown that HDF express only truncated/alternatively spliced POMC mRNA variants, which are probably biologically relevant as they could be translated to POMC peptide, both constitutively and upon activation.

Micropapillary urothelial carcinoma (MPUC) is a rare aggressive variant of urothelial carcinoma, associated with advanced tumor stage, high tendency to invade lymphovascular spaces, and metastasize to lymph nodes and other organs. Therefore, it has a poor prognosis. One of the most prominent histological features is the presence of small, round empty spaces surrounding infiltrating tumor nests. If detected, even a small focus of micropapillary pattern may be therapeutically significant ; the higher proportion of micropapillary component, the worse the prognosis. Radical nephroureterectomy is the treatment of choice even in the setting of superficially invasive disease. Although, MPUC has been well studied in urinary bladder, only a few cases of MPUC in upper urinary tract have been described. We are describing a case of a 79-year old woman with micropapillary urothelial carcinoma involving ureter and review the literature of this rare entity. Keywords: transitional cell carcinoma - micropapillary carcinoma - ureter - urinary bladder.

In the mammalian kidneys, transport of various organic compounds (organic anions and cations, glucose) and water is mediated by specific proteins localized in the luminal and/or contraluminal cell membrane domains along the nephron, largely in proximal tubules. These transporters contribute to reabsorption and/or secretion of endogenous and xenobiotic organic compounds, including various anionic and cationic drugs that are used in human and veterinary medicine. Recent studies have shown that some of these transporters (“drug transporters”) contribute to development of drug resistance, drug-drug interactions, and drug-induced nephrotoxicity, whereas their malfunction due to truncated forms of proteins or point mutations in their genes can cause genetic diseases. In rodents (rats, mice, rabbits), many renal transporters exhibit sex differences in their protein and/or mRNA expression, whereas in pigs and humans, some transporters are absent, some exhibit localization in the cell membrane domains different from that in rodents, but the sex-related expression of thus far tested transporters could not been confirmed. For some transporters common to rodent, pig and human kidneys, species differences were observed in selectivity for substrates, distribution along the nephron, expression of mRNA and/or protein, sensitivity to inhibitors, and regulation of the activity. In addition, recent findings in this field in rodents revealed the species-related discrepancies in the expression of some transporters at the level of protein and their mRNA, e.g., sex differences in the transporter protein can exist with or without equivalent differences in the expression of its mRNA. Moreover, these two parameters can be in an opposite relationship. We, therefore, conclude the following: a) the data on renal transporters in one sex and species can not simply be regarded as relevant for other sex and species, b) posttranscriptional regulation may represent crucial mechanism in controlling the sex- and species-related protein expression of the renal transporters, c) various physiological, pharmacological, and toxicological findings related to the transporter-mediated handling of organic substances and water in the rodent kidneys do not reflect the situation in the pig and human kidneys, and d) the kidneys in pigs, not in rodents, may represent much better model for studying the human-related expression and functions of various renal transporters.

Prijenos različitih organskih spojeva (organski anioni i kationi, glukoza) i vode u bubrezima sisavaca posredovan je posebnim proteinima smještenim u luminalnoj i/ili kontraluminalnoj strani stanične membrane duž nefrona, glavninom u proksimalnim kanalićima. Ovi prijenosnici sudjeluju u reapsorpciji i/ili sekreciji endogenih i ksenobiotskih organskih spojeva, uključujući različite anionske i kationske lijekove koji se rabe u tretmanu bolesti u humanoj i veterinarskoj medicini. Nedavna istraživanja pokazala su da neki od dotičnih prijenosnika igraju ulogu u nastanku otpornosti na lijekove, međudjelovanju lijekova i lijekovima-izazvanu nefrotoksičnost, a njihova poremećena aktivnost zbog strukturne nesavršenosti ili točkastih mutacija može dovesti do genetske bolesti. U glodavaca (štakor, miš, kunić), neki bubrežni prijenosnici tvari iskazuju spolne razlike u ekspresiji proteina i/ili mRNA, a u bubrezima svinja i ljudi, neki prijenosnici su odsutni, neki su smješteni na staničnoj domeni suprotnoj od one u glodavaca, a spolna-ovisnost u njihovoj ekspresiji nije utvrđena. Za neke prijenosnike, koji su zajednički glodavcima i ljudima, primijećene su vrstne razlike u selektivnosti prema supstratima, lokalizaciji duž nefrona, razini ekspresije mRNA i/ili proteina, osjetljivosti na inhibitore, i regulaciji aktivnosti. Prema tome, a) podaci o bubrežnim prijenosnicima tvari u jednom spolu i vrsti na mogu se smatrati relevantnim za drugi spol i vrstu i b) različiti fiziološki, farmakološki i toksikološki rezultati, koji se odnose na prijenosnicima-posredovan tok organskih tvari i vode u bubrezima glodavaca, ne odražava stanje u humanim bubrezima.

Organic cation (OC) transporters mediate the transepithelial transport of various endogenous and xenobiotic cationic compounds, including drugs, in various mammalian organs. These transporters are responsible for absorption, reabsorption, and secretion of relevant metabolites in the kidney, intestine, liver, placenta and brain. Recent studies have demonstrated the involvement of OC transportes in drug-drug interactions, drug resistance, and drug-induced organ toxicity. A number of OC transporters from different protein families and species have been cloned and characterized, and their functional roles have been studied mainly in the kidney and liver (Koepsell et al.: Organic cation transporters. Rev Physiol Biochem Pharmacol 150:103-117, 2003). The most important OC transporters are grupped into the families SLC22 (OCT1, OCT2, OCT3, OCTN1, OCTN2), SLC47 (MATE1, MATE2), and ABCB (MDR1/P-gp). OCT1-3 represent polyspecific bidirectional transporters that mediate electrogenic, sodium- and pH-independent intracellular uptake of OC via facilitated diffusion. In the renal proximal tubule, these transporter are predominantly localized in the basolateral membrane, where they mediate the first step of the renal OC excretion. The second, exit step across the brush-border membrane is mediated by the electroneutral H+-OC exchangers MATE1 and MATE2-K, and by the ATP-driven efflux pump MDR1. Various OC transporters differ in localization, substrate specificity, inhibitor sensitivity, transport mechanism, and regulation (Koepsell et al.: Organic cation transporters. Rev Physiol Biochem Pharmacol 150:103-117, 2003 ; Ciarimboli and Schlatter: Regulation of organic cation transport. Pfluegers Arch Eur J Physiol 449:423-441, 2005). Recent studies have shown that some of the above mentioned OC transporters exhibit sex differences in renal expression in rats, mice and rabbits, which correlate with the renal excretion of relevant substrates (Sabolic et al.: Gender differences in kidney function. Pfluegers Arch Eur J Physiol 455:397-429, 2007). Sex differences in the expression of some OC transporters were observed concerning distribution within the same organ (different localizations along the nephron) and sex hormone-regulated mRNA and/or protein expression in the same localization. Species differences in some OC transporters have also been demonstrated concerning a) substrate selectivity, b) organ and tissue distribution, c) distribution within individual organs, d) levels of mRNA and/or protein expression in the same localization, e) sensitivity to inhibitors, and f) regulation. The examples for each phenomenon collected from the literature or obtained in own experiments, will be presented. Sex and species differences in the expression and localization of OCT1 and OCT2 along the rat, mouse, and human nephron will be elaborated in more detail. In contrast to previous reports, distinct sex differences in expression of these OCTs will be demonstrated in rats and mice, but not in humans. Overall, the data indicate that many physiological, pharmacological, and toxicological findings related to OC transport and transporters, obtained in rodents, do not reflect the situation in humans.

Sex and species differences in the mammalian organic cation transporters. Organic cation (OC) transporters mediate the transepithelial transport of various endogenous cationic compounds, xenobiotic and drugs in the kidney, intestine, liver, placenta and brain. These transporters are also responsible for (re)absorption or elimination of relevant metabolites. Recent studies have indicated the involvement of OC transportes in drug-drug interactions, drug resistance, and drug-induced organ toxicity. A number of OC transporters from different protein families and species have been cloned and characterized, and their functional roles in kidney and liver have been studied (1). The most important transporters for OC have been grupped into the families SLC22 (OCT1, OCT2, OCT3, OCT6, OCTN1, OCTN2), SLC47 (MATE1, MATE2), and ABCB (MDR1). OCT1, OCT2 and OCT3 represent polyspecific bidirectional transporters that mediate electrogenic, Na+- and pH-independent uptake of OC into cells via facilitated diffusion. In the kidney, these transporter (often sumarized as OCTs) are predominantly localized in basolateral membranes of proximal tubules, where they mediate the first step of the renal OC excretion. The second, exit step across the brush-border membrane is mediated by the electroneutral H+-OC exchangers MATE1 and MATE2-K, and by the ATP-driven efflux pump MDR1. In addition to substrate specificity, transport mechanism and turnover, the OC transporters differ in regulation and localization (1, 2). Recent studies have shown that some of the above mentioned OC transporters exhibit sex differences in renal expression in rat, mouse and rabbit, which correlate with the renal excretion of relevant substrates (3). Sex differences in the expression of some OC transporters were observed concerning distribution within the same organ (different localizations along the nephron) and sex hormone-regulated mRNA and/or protein expression in the same localization. Species differences in some OC transporters have also been demonstrated concerning a) substrate selectivity, b) organ and tissue distribution, c) distribution within individual organs, d) levels of mRNA and/or protein expression in the same localizations, and e) regulation. In the present contribution, examples for each phenomenon collected from the literature or generated in own experiments, will be presented. The presence of sex and species differences of OCT1 and OCT2 will be elaborated in more detail in rat, mouse and human kidneys by showing their expression and different localizations along the nephron. At variance to previous reports, distinct sex differences in expression of both, OCT1 and OCT2 will be demonstrated in rats and mice, but not in humans. Together, the summarized and newly presented data emphasize that the use of rodents in studying (re)absorption, excretion, interaction and toxicity of OC does not reflect the situation in humans. References: 1) Koepsell H et al. (2003) Organic cation transporters. Rev Physiol Biochem Pharmacol 150:103-117 ; 2) Ciarimboli G and Schlatter E (2005) Regulation of organic cation transport. Pfluegers Arch – Eur J Physiol 449:423-441 ; 3) Sabolic I et al. (2007) Gender differences in kidney function. Pfluegers Arch – Eur J Physiol 455:397-429.

Invertirani papilom mokraćnog mjehura i urotelni karcinom invertiranog načina rasta često je teško razlikovati isključivo na temelju morfoloških kriterija. U radu su prikazana 4 bolesnika s urotelnim karcinomom invertiranog načina rasta i te se diskutira o diferenciranju istog od papiloma na temelju konvencionalne histologije i dodatnih pretraga.

Introduction. In the mammalian nephron, a high affinity/low capacity SGLT1 (SLC5A1) and a low affinity/high capacity SGLT2 (SLC5A2) have been identified as the major mediators of Na+-dependent hexose reabsorption. Our immunochemical studies in rats have shown the presence of both transporters in various organs and strong female-dominant sex differences in their expression in proximal tubules (PT) (Balen et al.: Am. J. Physiol. Cell. Physiol, 295:475-489, 2008 ; and unpublished data). Both SGLTs exhibit 59% homology and some functional and localizational differences. Functional studies in renal tubules and in isolated membranes have shown that SGLT1 transports equally well galactose and glucose, and has been localized to the brush-border membrane (BBM) of PT and small intestine (SI), while SGLT2 transports glucose much better, and has been detected in the BBM of PT. Due to lack of specific antibodies, a detailed immunolocalization of SGLT1 and SGLT2 in the human kidneys (K) and other organs has not been performed. Materials and Methods. A novel, highly specific rabbit-raised polyclonal antibodies against the human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) proteins were used to study their expression in kidneys (K), SI (jejunum), and liver (L) in humans of both sexes by Western blotting (WB) in isolated total cell membranes (TCM) and by immunocytochemistry (IC) in tissue cryosections. Results. In WB of the K and SI membranes, the hSGLT1 protein was identified as the 75 (K)-80 (SI) kDa band, while the hSGLT2 protein appeared as the 75 kDa band in the K membranes, which was not detected in the SI membranes. The WB studies in TCM from the K cortex (CO) and outer stripe (OS) revealed the presence of zonal (hSGLT1: CO < OS ; hSGLT2: CO > OS) but absence of sex differences in the expression of both hSGLTs. By IC in K, hSGLT1 was restricted to the BBM of PT S3 segments in the OS and medullary rays. In SI, hSGLT1 was detected in: a) BBM and subapical vesicles of absorptive cells, b) apical membrane of crypt epithelium, and c) sporadic individual cells in villous epithelium. A significant hSGLT1-positive staining was also observed in the apical domain of bile ducts in L. Prominent hSGLT2-specific staining was localized to the BBM of PT S1/S2 segments in the K CO, and to the apical domain and/or intracellular organelles in individual, enteroendocrine-type cells scattered among absorptive and crypt cells. In L, no hSGLT2-staining was detected. Conclusion. Our data confirm that hSGLT1 is critically involved in glucose and galactose absorption in SI, and for reabsorption of these monosaccharides in the renal PT S3 segments and liver bile ducts, while hSGLT2 is mainly engaged in glucose reabsorption in the renal PT S1/S2 segments. Both hSGLTs may contribute to regulation of glucose absorption via the enteroendocrine-type cells in SI.

Karcinom prostate je jedan od vodećih zdravstvenih problema muškaraca druge i tre¬ će životne dobi. Na njega otpada značajan udio od ukupnog broja svih malignih bolesti u muškaraca starijih od 50 godina, a incidencija se povećava svakim desetljećem, te je on na Zapadu najčešća maligna bolest muške populacije i drugi uzrok smrti. Nagli porast incidencije rezultat je starenja populacije, stoga i po¬ rasta udjela muškaraca u rizičnoj dobi. Sve bolja informiranost, šira primjena dijagnostičkih testova kao što je prostata specifični antigen (PSA) i transrektalna biopsija prostate doveli su do porasta broja bolesnika u kojih je dijagno¬ sticiran lokalizirani karcinom. Do sada su potvrđeni faktori rizika: dob, rasa, karcinom prostate u obitelji, dijeta i hormoni. Odavna je poznato da prostatitis, benigna hi¬ perplazija prostate i karcinom mogu koegzistirati u prostati, no još nije jasna povezanost između karcinoma i upale u prostati. Ipak, u novijim publikacijama sve je više dokaza o direktnoj ili indirektnoj povezanosti kronične upale i/ili infekcije i karcinoma prostate. Kritičkim pregledom važnijih recentnih epidemioloških stu¬ dija i metaanaliza vidi se da muškarci koji su preboljeli prostatitis ili spolno prenosive bolesti imaju povišen rizik od karcinoma prostate. Kronična upala povezuje se s razvojem mnogih malignih bolesti, uključu¬ jući tumore jednjaka, želuca, jetre, mokraćnog mjehura, debelog crijeva. Gotovo svi ti tumori pove¬ zuju se sa specifičnim infektivnim agensom ili okolišnim faktorima. Neovisno o etiologiji, smatra se da kronična upala u prostati kao reakcija na patogen inducira karcinogenezu oštećenjem stanica i/ili genoma, te stvaranjem tkivnog mikrookoliša bogatog citoki¬ nima i faktorima rasta koji izazivaju replikaciju stanica, angiogenezu i reparaciju tkiva. Za molekularnu patogenezu karcinoma prostate vezane su i somatske alteracije gena koji su angažirani u obrani protiv upalnog oštećenja stanica te u proce¬ su regeneracije stanica. Novija saznanja iz područja epidemiologije, genetike, molekular¬ ne patologije i upalne toksikologije sugeriraju da su kronični upalni procesi u prostati direktno upleteni u patogenezu karcino¬ ma prostate. S druge strane, potvrđeno je da upala u prostati svojim učinkom na porast vrijednosti serumskog PSA biokemijski imitira karcinom, na taj način smanjuje njegovu osjetljivost i specifičnost u ranoj detekciji, te se znatan udio bolesnika nepotrebno podvrgava ponavljanim biopsijama prostate. Međutim, nedostaju jasne preporuke za primjenu ovih saznanja u kliničkoj praksi. U literaturi još nisu jasno definirane indikacije za ponavljanje biopsije prostate niti koliko puta biopsiju treba ponavljati. Nije jasno treba li prisutnost upalnog infiltrata u nalazu biopsije prostate bez karcinoma interpretirati kao bezazleni nalaz ili ga treba smatrati induktorom karcinogeneze i indikacijom za pomnije praćenje bolesnika i ranije ponavljanje biopsije. Prepoznavanje i procjena upalnog infiltrata može pomoći u procjeni i daljnjem odlučivanju nakon negativne biopsije prostate u bolesnika povišenog rizika, te u razumijevanju uzroka abnormalnog porasta ukupnog PSA i pada slobodnog PSA. Veliku nadu u budućim planovima prevencije karcinoma prosta¬ te pružaju upravo strategije u smislu prevencije i liječenja upalnih bolesti prostate i spolno prenosivih bolesti. Buduće strategije u kemoprevenciji i ranoj detekciji raka prostate koje proistječu iz ovih saznanja uključuju: 1/ antioksidanse ; 2/ protuupalne lijekove (antiflo¬ gistike) ; 3/ sprečavanje, otkrivanje i antimikrobno liječenje prostatitisa. Kritički je prikazana recentna literatura.

In the mammalian kidney, transport of endogenous and xenobiotic organic compounds is mediated by multispecific organic anion and cation transporters localized in the apical and basolateral cell membrane domains of the specific nephron segments. These transporters are also responsible for drug resistance, drug-drug interactions, and drug-induced nephrotoxicity. In rat and mouse proximal tubules, a number of these transporters exhibit sex differences in their expression. In comparison with those in rodents, in pig and human proximal tubules some transporters are absent, some exhibit different localization in the cell membrane domains, and none exhibits the sex-dependent expression. These differences indicate that: a) the data on renal transporters in one species can not simply be regarded as relevant for other species, and b) pigs may be better model then rodents for drug-related studies relevant to humans.

Benigna hiperplazija prostate (BHP) jedna je od najčešćih dijagnosticiranih oboljenja u odraslih muškaraca, vezana je uz starenje i karakterizirana je porastom broja epitelnih i stromalnih stanica u periuretralnom području prostate. Klinička manifestacija BHP i smetnje donjeg utrotrakta koje izaziva znatno smanjuju kvalitetu života bolesnika. Oboljenje se javlja u više od trećine muškaraca starijih od 60 godina. U predavanju su prikazani epidemiologija, etiologija, patogeneza, dijagnostika, te aktualne preporuke za medikamentoznu i kiruršku terapiju.

Naknadno upisati

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A high affinity/low capacity SGLT1 (SLC5A1) and a low affinity/high capacity SGLT2 (SLC5A2) have been identified as the major mediators of Na+-dependent hexose reabsorption in the mammalian nephron. The human transporters exhibit 59% homology and some functional and localizational differences. hSGLT1 transports equally galactose and glucose, and has been localized to the brush-border membrane (BBM) of renal proximal tubules (PT) and small intestine (SI), while hSGLT2 transports glucose much better, and has been detected only in PT. Due to lack of specific antibodies, a detailed immunolocalization of hSGLT1 and hSGLT2 in the human kidney (K) and other organs has not been performed. In this work we used novel polyclonal antibodies against both transporters, and studied their expression in K, SI (jejunum), and liver (L) in humans of both sexes by Western blotting (WB) in isolated total cell membranes (TCM) and by immunocytochemistry (IC) in tissue cryosections. In WB, the hSGLT1-protein band (Mr ~75 kDa) was detected in both K and SI, whereas the hSGLT2-protein band with similar Mr was detected only in K. The studies in TCM from the K cortex (C) and outer stripe (OS) revealed strong zonal (hSGLT1: COS) but no gender differences in their expression. By IC in K, hSGLT1 was restricted to the BBM of S3, while hSGLT2 was localized to the BBM of S1 and S2 segments of PT. In SI, hSGLT1-antibody labeled the ~80 kDa protein band, and stained: a) BBM and subapical vesicles in absorptive cells, and b) apical domain in crypts, with similar intensity in both sexes. In L, hSGLT1-positive was the apical domain of bile ducts. hSGLT2 was absent from both SI and L. Our data indicate that in humans, SGLT2 may serve the Na+-gradient-driven sugar reabsorption exclusively in the convoluted segments of PT in K, whereas SGLT1 may mediate sugar absorption in SI and reabsorption in the straight segment of PT in K and in bile ducts in L.

MIkropapilarni urotelni karcinom (MUK) je rijetka varijanta urotelnog karcinoma mokraćnog mjehura (UK) koja ima veoma agresivno ponašanje. U ovoj studiji analizirali smo kliničkopatološka obilježja MUK, posebno odnos između patohistološkog stupnja u trenutku otkrivanja bolesti i udjela mikropapilarne komponente (MPK) u pregledanom materijalu za 10 bolesnika koji su liječeni zbog urotelnog karcinoma mjehura u razdoblju od 1.1.2004.-30.6.2007. u KB Sestre Milosrdnice. U promatranom razdoblju bilo je 610 bolesnika s UK mjehura (M:F=456:154) od kojih je 10 imalo MUK. Svi mikropapilarni urotelni karcinomi bili su u invazivnom stadiju bolesti u vrijeme postavljanja dijagnoze. Raspodjela po stadijima bila je 4T1 (40%) i 6 T2 (60%), a udio MPK bio je: u 3 od 4 (75%) T1 tumora manje od 10% MPK, dok je u 5 od 6 (83, 2%) T2 tumora bilo više od 50% MPK. MUK je agresivni tumor, obično u uznapredovalom stadiju u vrijeme otkrivanja bolesti, kod kojeg je patološki stadij povezan s udjelom MPK u tumoru.

Karcinom prostate je u novije vrijeme prepoznat kao jedan od vodećih zdravstvenih problema muškaraca druge i treće životne dobi. Maligni je tumor na koji otpada značajan udio od ukupnog broja svih malignih bolesti u muškaraca starijih od 50 godina, a incidencija se povećava sa svakim desetljećem, te on predstavlja najčešću malignu bolest muške populacije i drugi uzročnik smrti, odmah iza karcinoma pluća. Iako etiologija karcinoma prostate još uvijek nije poznata, verificirano je više faktora koji povećavaju rizik za nastanak bolesti. Do sada su poznati faktori: dob, rasa, karcinom prostate u obitelji, dijeta i hormoni. Za sada ima malo dokaza da benigna hiperplazija prostate, pretilost, smanjena tjelesna aktivnost, pušenje, izlaganje zračenju ili seksualno prenosivi virusi povećavaju rizik od razvoja karcinoma prostate. U recentnim publikacijama sve je više dokaza od direktnoj ili indirektnoj povezanosti kronične upale i/ili infekcije i karcinoma prostate. Prikazano je nekoliko važnih epidemioloških studija koje su dokazale da postoji povišeni relativni rizik od razvoja karcinoma prostate u muškaraca s preboljelim spolno prenosivim bolestima ili prostatitisom. Odavna je poznato da prostatitis, benigna prostatična hiperplazija i karcinom mogu koegzistirati u prostati, no još nije jasna povezanost između karcinoma prostate i histološki definirane upale u prostati. Novija istraživanja sugeriraju da imunološki i upalni modulatori mogu imati ulogu u hiperplastičnom rastu i proliferaciji prostatičnih epitelnih stanica muduliranjem djelovanja citokina. Sugerira se da je glavni mehanizam karcinogeneze oksidativno oštećenje genoma stanice prostate izazvano upalnim stanicama i lokalnim imunološkim mehanizmima. Zapravo je upala u prostati povezana s oksidativnim oštećenjem genoma uzrokovanim oslobađanjem slobodnih radikala. Za molekularnu patogenezu karcinoma prostate vezane su i somatske alteracije gena koji su angažirani u obrani protiv upalnog oštećenja stanica, te procesu regeneracije stanica. Uz prostatičnu intraepitelnu neoplaziju, atipičnu proliferaciju malih stanica, kao prekursore karcinoma prostate, sve više se spominje termin proliferativna inflamatorna atrofija. Ova lezija pokazuje karakteristike stanica koje su oštećene od strane imunološkog sistema i pokazuju regenerativnu proliferaciju. Sve tri promjene sadržavaju gentičke i epigenetičke promjene slične karcinomu prostate. Sada se navodi da je ova, zapravo upalna lezija, gotovo sigurno prekursor karcinoma prostate. Prikazani su molekularni modeli upalne karcinogeneze prostate. Kritičkim pregledom važnijih recentnih metaanaliza koje su analizirale povezanost upale i karcinoma prostate vidi se da muškarci koji su preboljeli prostatitis ili spolno prenosive bolesti imaju znatno povišen rizik od karcinoma prostate. Veliki napredak u molekularnoj patologiji i naše bolje razumijevanje upale toksikologije i njenog učinka na oštećenje, regeneraciju, proliferaciju i karcinogenezu stanica još više podupire hipotezu o direktnoj povezanosti kronične upale i karcinoma prostate. Veliku nadu u budućim planovima prevencije karcinoma prostate pružaju upravo strategije u smislu prevencije i liječenja upalnih bolesti prostate i spolno prenosivih bolesti. Novije strategije u prevenciji koje proistjeću iz ovih saznanja uključuju: 1/ antioksidanse ; 2/ konzumiranje hrane bogate antioksidansima ; 3/ protuupalne lijekove (antiflogistike) ; 4/ sprečavanje, otkrivanje i liječenje spolno prenosivih bolesti koji mogu uzrokovati kroničnu upalu prostate.

Prikazujemo bolesnika s karcinomom bubrežnih stanica i urotelnim karcinomom nakapnice i mokraćovoda lijevog bubrega. Bolesniku je prije devet godina odstranjen desni bubreg zbog karcinoma bubrežnih stanica. Do sada je u engleskoj literaturi opisano 25 slučajeva istovremene pojave karcinoma bubrežnih stanica i urotelnog karcinoma istostranog bubrega. Srednja dob u vrijeme postavljanja dijagnoze je oko 65 godina, najčešći klinički simptom je hematurija, a 24% pacijenata ima metastaze pri prvom pregledu. Otprilike četvrtina je pušača, te se smatra da je pušenje zajednički etiološki čimbenik za te dvije vrste tumora. Nema dokaza da se pri zajedničkom pojavljivanju ta dva tumora nalazi viši gradus malignosti, niti specifičan histološki obrazac. Prema podacima iz literature do sada nije opisana istovremena pojava karcinoma bubrežnih stanica i istostranog urotelnog karcinoma nakapnice i mokraćovoda.

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Introduction & Objectives: Methylentetrahydrofolate reductase (MTHFR) is the most important enzyme involved in DNA methylation process and converts 5, 10-methyltetrahydrofolate to 5-methyltetrahydrofolate. The C677T polymorphism of the MTHFR gene is associated with 70% lower enzyme activity and hypomethylation. many studies investigated the role of MTHFR polymorphism in cancer susceptibility and though most authors report lower frequency of mutated T allele in cancer patients, results are still inconclusive. The aim of this studa was to asses the frequency distribution of mutated T allele in the patients with prostatic cancer (PC) and benign prostatic hyperplasia (BPH). material & methods: The case control study comprised of 45 patients with BPH and 95 patients with prostatic cancer. For the patients with carcinoma, Gleason score was determined as an index of degree of malignancy. PCR-RFLP method was used to determine MTHFR C677T polymorphism. Results: Genotypes in both groups were in Hardy-Weinberg equilibrium. Proportions of genotypes in PC group were C/C=0.40, C/T=0.51 and T/T=0.09 and in the BPH group C/C=0.47, C/T=0.42 and T/T=0.11. There was no statistically significant difference in genotype distribution between groups (P=0.6558). Odds ratio and 95% confidence interval for the C/T genotype was 1.3961(0.658-2.963) and for the T/T genotype 0.9947(0.295-3-357). Proportions in the group of patients with prostatic cancer of lower malignancy (Gleason score 4-6) were C/C=0.39, C/T=0.47 and T/T=0.14 ; and in the group with more malignant prostatic cancer (Gleason score 7-9) C/C=0.40, C/T=0.53 and T/T=0.07. Proportions between groups with higher and lower malignancy were not different (P=0.8693). Conclusions: results of our research didn't provide any evidence for the association of MTHFR C677T polymorphism with prostate cancer risk.

Serum levels of total prostate specific antigen (t-PSA) and PSA complexed to antichymotrypsin (PSA-ACT), as well as their corresponding density parameters were measured in prostate cancer (PC) candidates for radical prostatectomy. In these patients blood Chromogranin A (CgA) values were also recorded. The PSA-ACT recordings in presurgically characterized organ-confined disease were assumed to predict post-surgical staging better than t-PSA. If this proved correct the novel approach might contribute to the positive predictive value of Partin nomograms. In this prospective study 50 patients with clinically localized PC underwent staging pelvic lymphadenectomy and radical prostatectomy. The numerical values of the tPSA and PSA-ACT parameters were presurgically measured. The PSA and PSA-ACT densities (PSAD and ACTD) of the whole prostate were calculated by using transurethral ultrasound (TRUS) data. These preoperative results together with the CgA values were correlated with post-surgical pathological staging data. The relationships between serum tPSA, PSA-ACT, PSAD, ACTD, CgA and the final stage of prostatectomy specimens derived from the pathological data were analyzed. This preliminary study was performed on a relatively small number of patients who were characterized by a serum PSA

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We report a patient with ipsilateral synchronous renal cell carcinoma and urothelial carcinoma of the left renal pelvis and ureter. The patient underwent nephrectomy 9 years earlier due to renal cell cancer of the right kidney. Only 25 cases of ipsilateral synchronous renal cell carcinoma and urothelial carcinoma have been reported in the literature. The median age at diagnosis was 65 years, hematuria was the most common presentation and 24% of patients had metastases at first examination. Approximately one fourth of the patients had a history of cigarette smoking. There is no proof about higher histopathological grade of malignancy or specific histological pattern of these tumors when they occur synchronously. In the literature there is no report on the synchronous occurrence of renal cell carcinoma and urothelial carcinoma of both the renal pelvis and ipsilateral ureter.

Based on our experience at this institution, transvesical reinplantation by Cohen and Gil-Vernet tehiques is a reilable procedure and our results are comparable to those reported from other institutions. We demonstrated the surgical treatment of VUR to be both safe and successful, with a low postoperative compications.

Recommendations for antimicrobial treatment and prophylaxis of urinary tract infections (UTI) have been made according to study results on the resistance of the most frequent causative agents of UTI to antimicrobial drugs. The Committee for monitoring bacterial resistance to antibiotics in the Republic of Croatia has been conducting this study since 1997. Uncomplicated cystitis is treated for 1, 3 or 7 days, complicated cystitis for 7 days, pyelonephritis 10-14 days, and complicated UTI7 to 14 days, rarely longer. For the treatment of cystitis the following drugs are used: fluoroquinolones, nitrofurantoin, betalactam antibiotics, and in cases of lower resistance trimethoprim- sulfamethoxazole. A single therapy with fluoroquinolones is administered to otherwise healthy young women with normal urinary tract in whom cystitis symptoms have been present for less than 7 days. Empirical antimicrobial therapy of pyelonephritis, recurrent and all complicated UTIs must be reviewed after urine culture finding is obtained. In the treatment of bacterial prostatitis and febrile UTIs in males, the drug of first choice is ciprofloxacin. Asymptomatic bacteriuria is treated in pregnant women, newborns, preschool children with urinary tract abnormalities, before invasive urological and gynecological procedures, in kidney transplant recipients, and in the first days of short-term urinary bladder catheterization. Antimicrobial prophylaxis is administered primarily one hour prior to diagnostic or therapeutic invasive urological procedures, using selected antimicrobial agents.

Our study demonstrated that prostate biopsy is an intervention relatively well tolerated by patients with the complications that are neither dangerous nor too frequent. In most cases they included hematuria , however, manifesting at a significantly lower rate than reported elsewhere, and resolved spontaneously. In case of infections , they responded well to antibiotic teraphy, so that hospitalization was required in les than 1% of patients. the level of pain during and after prostate biopsy wasassessed by the patients as low, although it is an unppleasant invasive diagnostic examination. If the benefits are weighed against complications, the performance of prostate biopsy will certainly prove justifiable on the outpatient basis and without the need of local or regional anesthesia.

Radical prostatectomy is a treatment of choice for localized prostatic adenocarcinoma. In most cases, radical prostatectomy is combined with pelvic lymph node dissection. During the last decade, the necessity to perform lymphadenectomy in all patients has been questioned. Lymph node dissection adds the risk of complications, and increases operation time and medical costs. Data of patients with pros- tatic adenocarcinoma who underwent radical prostatectomy at Department of Urology, Sestre milosrdnice University Hospital, Zagreb during the period from January 1, 1998 till December 31, 2002, were analyzed. There were 110 patients who had complete preoperative data including prostate-specific antigen (PSA) value, Gleason score, T stage and lymph node status on frozen section analysis. Using predictive nomo- grams the patients were divided into different risk groups. Positive lymph node(s) were found in one patient with T2 and in five patients with T3, whereby three, two and one of these patients had Gleason score 6, 7 and 8, respectively. There was a correlation between increasing PSA value and positive lymph nodes (p

True hermaphroditism represents a heterogeneous condition in terms of its phenotypic presentation and genetic background. There is a wide spectrum ranging from frankly male to frankly female external genitalia, however, with a predominance of ambiguity. The most frequently observed cerotype is 46, XX, followed by various types of chromosome mosaicism, whereas the rarest one is 46, XY. Simultaneous presence of testicular and ovarian tissue either in separate gonads or in one named ovotestis is required for the diagnosis. In neonatal period our patient was noted to have isolated clitorimegaly (15 mm) with otherwise normal female external genitalia and no palpable gonads either in labia or in inguinal areas. The levels of electrolytes, 17-hydroxyprogesterone (17 OH P), androstendione and renin were within the reference values. Baseline plasma level of testosterone was elevated as well as its response in the human chorionic gonadotropin (hCG) stimulation test. The presence of uterus was discovered by imaging techniques but gonadal localization was not possible. Karyotype was 46, WY. According to clinical and laboratory findings, the diagnosis of 46, XY partial gonadal dysgenesis was made. During surgery, reduction of clitoris was performed while laparotomy revealed a right ovotestis (confirmed by histology), which was removed. The left gonad was not identified and biopsy of suspected tissue revealed fallopian tube. Considering obvious female appearance of external genitalia and its potential function, it was suggested that the baby should be reared as a girl. As there is no clinical, laboratory or imaging finding which could differ true hermaphroditism from some other types of intersex, definitive diagnosis depends on gonadal histology.

Due to the rarity of multiple primary synchronous malignancies, the correct and concurring data on their incidence are extremely difficult to find. Recent studies point to renal cell carcinoma as a tumor showing most prominent association with other types of simultaneous or metachronous primary carcinoma. To our knowledge, this is the first case of multiple primary adenocarcinomas of the kidney, prostate, and urothelial carcinoma of the urinary bladder associated with primary sigmoid adenocarcinoma and colostomic metastasis analyzed for p53 loss of heterozygosity., Višestruki primarni sinkroni maligniteti su vrlo rijetki, pa je iznimno teško naći točne i sukladne podatke o njihovoj incidenciji. Novija ispitivanja ukazuju na karcinom bubrežnih stanica kao na tumor koji pokazuje najizrazitiju udruženost s drugim vrstama istodobnih ili metakronih primarnih karcinoma. Prema našim saznanjima, ovo je prvi slučaj višestrukih primarnih adenokarcinoma bubrega, prostate i urotelnog karcinoma mokraćnog mjehura udruženih s primarnim sigmoidnim adenokarcinomom i kolostomnim metastazama analiziranih na p53 gubitak heterozigotnosti.

Base on our data and recent literature review, it is concluded that the prevalence of false-negative TRUS guided biopsies is significa. In our series, 32% of patients had carcinoma ond repeat biopsy.Also, more than 20% of these cancers were decetdet in transition zone of tprostatic neoplasms, pathology, biopsyrostate gland, so transition zone biopsy is strongly recommended.We recommend repeat TRUS guided biopsy including transition zone assessment in all patients who meet the criteria for such biopsy and in whom lnitial biopsy was negative. The procedure is wel toleratedo be suitpatient setting and is associated with a minimal complication rate.

During the last 20 years, the occurrence of some diseases has changed due to a different way of living and new diagnostic and treatment possibilities. Diagnostic imaging (CT, MR and especially ultrasound) has increased the rate of identification of renal tumors, while there has not been any systematic screening for urologic diseases. Department of Urology is a referral center for prostate diseases since 1994. The procedure of needle core biopsy was introduced two years later and its utilization has increased significantly over the last few years. In the present study, the occurrence of some urologic diseases was compared at 20 years apart using the histopathologic database for 2 two-year periods. Data on all patients who underwent biopsies at Department of Urology during the 1980-1981 and 2000-2001 periods were included in the study. In the 1980/81 period, tissue samples of 25, 117 patients were analyzed at Department of Pathology, 1070 (4.3%) samples being obtained from urologic patients. In the 2000/01 period, there were 27, 720 patients, 2, 233 (8%) of them from Department of Urology. Urogenital tract tuberculosis was found in 13 (1.2%) patients during the 1980/81 period, and in only two (0.1%) patients in the 2000/01 period. In the 1980/81 and 2000/01 periods, there were 13 (1.2%) and 102 (4.6%) renal cell carcinomas, respectively. Of all urologic biopsies in the first period there was only one (0.1%) case, and in the 2000/01 period there were 17 (0.8%) cases of urothelial carcinoma of the pyelon. In the 1980/81 period there was not a single case of oncocytoma, whereas in the 2000/01 period 3 cases of oncocytoma were recorded. There were 106 (10%) and 64 (0.2%) testicular biopsies in the total number of urologic patients in the 1980/81 and 2000/01 periods, respectively. Of all testicular biopsies there were 13 (12%) and 29 (45%) tumors of the testis in the 1980/01 and 2000/01 periods, respectively. Seminoma accounted for 30% (n=4) and 55% (n=16) of all germ cell tumors in the 1980/81 and 2000/01 periods, respectively. Of the total number of urology biopsies performed in 1980/81 and 2000/01, there were 416 (38.8%) and 963 (43%) prostate biopsies, respectively, 59 (14 %) of them carcinomas in 1980/81 and 222 (23 %) carcinomas in 2000/01. An increasing number of prostate biopsies was recorded in the 2000/01 period, mainly due to the large proportion of needle core biopsies (304 of 966 prostatic biopsies). Prostatic biopsies accounted for 40% of all urologic biopsies in 2000 and for 46% in 2001. On the basis of this study it is concluded that the total number of urologic biopsies increased 1.9-fold comparing the first (1980-1981) and second (2000-2001) period. There was a significant increase in the number of renal cell carcinoma (3.8-fold) and urothelial carcinoma of the pyelon (8.4-fold). The total number of testicular biopsies decreased, whereas the number of testicular tumors and seminomas increased. Tuberculosis of the urogenital system decreased 13-fold.