IDIOPHATIC ASYNCHRONOUS BILATERAL SEGMENTAL TESTICULAR INFARCTION AND ANTICOAGULANT THERAPY: A CASE REPORT.

We present an unusual case of sudden onset of pain in the left testis in a patient with a previous medical history of right orchiectomy due to hemorrhagic infarction. A partial orchiectomy was performed with complete removal of the lesion and reconstruction of the testicular parenchyma. Histopathological assessment confirmed segmental testicular infarction without the presence of malignancy. The patient subsequently received anticoagulant therapy.

MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia.

Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (p = 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA >10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification.

Association of Triiodothyronine Levels With Prostate Cancer Histopathological Differentiation and Tumor Stage.

BACKGROUND/AIM: The aim of this study was to determine the association between total triiodothyronine (T3), free fraction of thyroxin (FT4), and thyrotropin (TSH) levels with prostate cancer histopathological features. PATIENTS AND METHODS: Blood samples from 140 patients with prostate cancer were analyzed preoperatively and stratified according to postoperative histopathological differentiation. The first group (N=62) included patients with prostate cancer Grade Groups (GG) 1-2, while the second group (N=63) included patients with prostate cancer GG 3-5. RESULTS: T3 levels were significantly higher in patients with prostate cancer GG 3-5 (p=0.047). There was no significant difference in the FT4 and TSH levels between the two groups (p=0.680 and 0.801, respectively). T3 levels were positively correlated with tumor percentage involvement (TPI) (p=0.002), and pT stage (p=0.047) on definitive pathology. CONCLUSION: Higher T3 levels are associated with several indicators of prostate cancer histopathological aggressiveness.

Collecting duct carcinoma and endemic nephropathy - case reportS and literature review.

Although collecting duct carcinoma is a subtype of renal cell carcinoma, several studies implicate association with urothelial carcinoma. The coexistence of collecting duct carcinoma and another renal neoplasm is rare. Endemic nephropathy is a renal disease causing chronic renal failure. It is highly associated with urothelial neoplasm and occurs in endemic villages in Bosnia, Croatia, Bulgaria, Romania and Serbia. Recent studies have confirmed the important role of exposure to aristolochic acid as an etiologic factor. We present three cases of collecting duct carcinoma with literature overview. In one case, we describe collecting duct carcinoma with metachronous urothelial carcinoma of the pyelon and urinary bladder in an endemic nephropathy patient. To our knowledge, this is the first case report describing this coexistence. Certain similarities between collecting duct carcinoma and urothelial carcinoma were found, e.g., higher incidence in female compared to male, higher mean age, and multifocal and multicentric occurrence of the tumor. Our observations support the hypothesis that collecting duct carcinoma and urothelial carcinoma could be connected.

PROSTATE CANCER DIAGNOSIS IN 2019 - CHANGES IN EUROPEAN GUIDELINES AND IMPACT ON DAILY PRACTICE.

Changes in the diagnostic pathway for prostate cancer advised in the most recent Guidelines of the European Association of Urology bring many endeavors for everyday practice. Availability, costs and radiological expertise are still representing a challenge for the adoption of these guidelines in everyday clinical practice. In this article we discuss the current situation regarding these issues and future options.

History of Urology at the Sestre Milosrdnice University Hospital Center.

The history of Croatian urology clearly shows its affiliation to the medical and civilizational circle of the Western world. The Department of Urology at the Sestre milosrdnice University Hospital Center is the oldest urology institution in the Republic of Croatia. The Department was established in 1894, when the new Sestre milosrdnice Hospital was open in Vinogradska cesta in Zagreb. It was then that doctor Dragutin Masek founded the so-called III Department, which, in addition to treating urology patients, also treated patients with conditions of the ear, nose and throat, eye diseases and dermatologic conditions. Dragutin Masek had already realized that medicine would soon be divided into fields and had assigned younger doctors joining the III Department to specific fields. As a result, urology was given to Aleksandar Blaskovic, who founded the first independent department of urology in Croatia in 1926. In 1927, he was appointed Professor of urology at the Zagreb School of Medicine, where he established the first department of urology and was giving lectures and practicals. Under his leadership, the Department of Urology was given the status of a Clinic, a teach-ing department, the first of its kind in Croatia. Owing to all his activities in the field of urology, the history remembers him as the "father of modern Croatian urology". Over the course of the following years, department chairs had changed, but luckily for the patients, approach to work had not. Conscientiousness, trust, competence and charity. After all, charity is the idea that the hospital carries even in its name, after the Sisters of Charity who had founded it. In all the decades, the Department of Urology has been following global development paths, objectively legging behind top facilities in the world by only a few years. Overall professional and scientific urology activities culminated in 1998, when the Clinic became the Reference Center of the Ministry of Health of the Republic of Croatia for prostate cancer, and in 2011, when it became the European Board of Urology Certified Center. All that has been achieved could not have been done without wholehearted help and cooperation of the nurses, as well as every other department employee from the beginnings of urology until today. Despite its rich history, the Department does not rest on laurels. Today, it is a modern urology department together with its European role models.

20 Years of the Reference Center for Prostate Tumors of the Ministry Of Health at the Department of Urology in Sestre Milosrdnice University Hospital Center.

The Department of Urology at the Sestre milosrdnice University Hospital Center is the oldest urological institution in the Republic of Croatia and this part of Europe. Today, the Department is a modern tertiary healthcare institution, where the most complex methods of urological practice are performed using modern medical devices and highly sophisticated technology. In 2011, our urology specialist education program was certified by the European Board of Urology (EBU) as the only one of its kind in Croatia. The program was recertified in 2017. The Department runs a program for the early detection of prostate cancer and performs more than 240 radical prostatectomies annually, which is the highest number of such interventions in Croatia. The aim of this study is to present the work and the activities of the Reference Center for Prostate Tumors of the Ministry of Health at the Department of Urology in Sestre milosrdnice University Hospital Center over the last 20 years. The database of the Reference Center for Prostate Tumors of the Ministry of Health at the Department of Urology in Sestre milosrdnice University Hospital Center was reviewed. During the twenty-year period, approximately 15,000 prostate interventions were performed due to benign and malignant diseases. Of this, 7,374 transrectal ultrasound guided prostate biopsies, 2,632 radical prostatectomies with open retropubic access, 3,988 transurethral prostate resections and 1,097 open suprapubic adenomectomies were performed. With the achieved scientific and professional results in monitoring, studying and improving the prevention, diagnosis and therapy of prostate tumors, as well as with the professional conditions and personnel, the Department of Urology in Sestre milosrdnice University Hospital Center truly justifies the title of the Reference Center for Prostate Tumors of the Ministry of Health of the Republic of Croatia awarded to it in 1998.

Epidemiology of Prostate Cancer in Croatia - Situation and Perspectives.

Prostate cancer represents a significant public health burden in Croatia, as well as in other developed countries. The aim of this paper was to present the current epidemiological situation in Croatia in comparison to other similar countries, using basic indicators such as incidence, mortality, prevalence and survival, and to discuss future possibilities in this field. The incidence of prostate cancer in Croatia has been rapidly increasing since the mid-nineties; recent data indicates that the trend is levelling off. Mortality data show constant increase since the 1960s, but mortality trends seem to be stabilizing in the recent period; however, Croatia is still in the top ten countries regarding prostate cancer mortality in Europe. Five-year prevalence in 2012 was estimated at 7,592 cases (426.7/100,000), ranking Croatia in the middle of European countries in the GLOBOCAN 2012 database. According to the CONCORD-2 study, five-year net survival in Croatia in the 2005-2009 period was 75.1%, which is lower than in similar European countries. The epidemiological pattern of prostate cancer in Croatia indicates a relatively low incidence, with significant room for improvement in mortality and survival data. Given the recent discussions regarding prostate cancer screening modalities, a debate is warranted and should be encouraged regarding the role of PSA testing in Croatia.

Role of Multiparametric Magnetic Resonance Imaging in Prostate Cancer Assessment.

Multiparametric magnetic resonance is assuming an increasingly important role in the diagnosis, initial assessment and monitoring of patients with prostate cancer. This paper offers a more complex insight into the application of magnetic resonance imaging with prostate cancer, with a current literature overview. The focus is on the problem of initial prostate cancer evaluation which strongly affects further decision-making and therapeutic interventions. Clinical suggestions based on the current guidelines are also offered.

Diagnostic Value of Cognitive-Registration Multiparametric Magnetic Resonance Guided Biopsy for the Detection of Prostate Cancer after Initial Negative Biopsy.

The aim of this prospective clinical study was to determine the detection rate of prostate cancers by multiparametric magnetic resonance and transrectal ultrasound (mpMRI-TRUS) cognitive fusion biopsies in patients with a previously negative TRUS-guided biopsy. Between 1 October 2016 and 1 July 2017, in 101 consecutive patients with elevated antigen (PSA) and/or positive digital rectal examination and after a negative first TRUS biopsy, a second, repeated prostate biopsy was performed. In 24 patients, cognitive fusion mpMRI-TRUS biopsy of the prostate with 8-10 system cores and 1-3 target biopsies was performed, in line with the European Association of Urology guidelines. In 77 patients, only a classic, repeated TRUS guided biopsy was performed. In patients with mpMRI, the detection rate according to PIRADS-v2 reporting system was: PIRADS 1, n = 0; PIRADS 2, n = 0; PIRADS 3, n = 0; PIRADS 4, n = 6/8 (75%); and PIRADS 5, n = 2/3 (67%). In the group of patients with MR-TRUS cognitive fusion biopsy, the prostate cancer detection rate was 8/24 (33%), while in the control group the detection rate was 12/77 (16%), which was statistically significant (t test, p = 0.037, CI 95% is 0.01 to 0.37). Patients with PIRADS ≤ 3 (54%) could have avoided the biopsy.

Cost-Benefit Analysis of the Introduction of Mp-Mri Guided Biopsies in Croatia.

The objective of this study was to determine differential expression of TFF1, TFF2 and TFF3 genes and proteins in breast tumor subtypes. In addition, we investigated the correlation between TFF genes within tumor subgroups, and TFF genes with clinical and pathologic characteristics of the tumor. Study group included 122 patients with surgically removed breast tumors. Samples were investigated using qRT-PCR and immunohistochemistry. TFF1 and TFF3 genes and proteins were expressed in breast tumors, while the levels of TFF2 gene and protein expression were very low or undetectable. TFF1 was significantly more expressed in benign tumors, while TFF3 was more expressed in malignant tumors. Gene and protein expression of both TFF1 and TFF3 was greater in lymph node-negative tumors, hormone positive tumors, tumors with moderate levels of Ki67 expression, and in grade II tumors. A strong positive correlation was found between TFF1 and TFF3 genes, and the expression of both negatively correlated with Ki67 and the level of tumor histologic differentiation. Our results suggest that TFF1 and TFF3, but not TFF2, may have a role in breast tumor pathogenesis and could be used in the assessment of tumor differentiation and malignancy.

Histopathological Outcomes after Radical Prostatectomy for Prostate Cancer Based On a New Grading System.

One of the main reasons for the introduction of a new grading system was Gleason sum 7, which differed significantly in the prognosis of the disease depending on the primary Gleason. The aim of this study was to compare grade group 2 and grade group 3, and the impact of cancer percentages in final pathology reports after radical prostatectomy on the occurrence of T3 stage of the disease after radical prostatectomy of clinically localized prostate cancer. The study covered 365 patients with clinically localized prostate cancer who underwent radical retropubic prostatectomy (RRP) over the period of two years. The average percentage of carcinomas found in pathology reports after RRP was 20.1%. With the increase in the grade group, the average percentage of carcinomas in pathology reports increased significantly, p <0.001. With regard to grade groups 2 and 3, irrespective of cancer percentages in pathology reports, more cases of T3 stage were found in grade group 3 when compared to grade group 2, which was statistically significant (p <0.001). However, grade group 2 and grade group 3 patients with ≤10% cancer occurrences in final pathology reports after RRP did not show any statistical significance in the occurrence of T3 stage, p=0.96. Prognostic differences in grade group 2 and grade group 3 patients after RRP are significant, but not in all cases, because of their dependence on the percentage of cancer in the final pathology report after RRP of clinically localized prostate cancer.

Expression of LMO2 in Prostate Carcinoma and Adjacent Prostatic Parenchyma.

LMO2 (LIM domain only) is a member of transcription factor family of proteins characterized by their cysteine-rich, zinc-binding LIM domains. Its expression in prostate cancer cells, as well as in adjacent stroma, is described in a study in a cohort of 83 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. Authors found that LMO2 overexpression in prostate cancer was strongly associated with features indicative of worse prognosis (higher preoperative PSA, higher Gleason score, positive surgical margins, and extraprostatic extension of disease). Expression of LMO2 was also associated with biochemical disease progression. We analysed immunohistochemical expression of LMO2 in prostate cancer epithelial and stromal cells, as well as in adjacent parenchyma. Significant negative correlation between glandular expression of LMO2 in carcinoma and stromal expression in BPH (ρ = -0.238, P = 0.033) was found, but also be-tween stromal expression in carcinomas and glandular expression in BPH (ρ = -0.255, P = 0.021). Positive correlation was found between stromal expression in BPH and stromal expression in carci-nomas (ρ = 0.306, P = 0.005). Study results support the potential role of LMO2 in prostatic carcino-genesis and cancer progression.

Unfavorable Clinicopathological Features in Radical Prostatectomy Patients Who Were Spared Pelvic Lymphadenectomy.

Pelvic lymph node dissection (PLND) during radical prostatectomy (RP) is the most accurate staging modality for lymph node assessment in patients with prostate cancer. It is recommended in all patients with intermediate or high-risk disease undergoing radical prostatectomy. The goal of our study was to assess unfavorable clinicopathological characteristics in patients with omitted lymphadenectomy (PLND) during radical prostatectomy based on the nomogram proposed by Briganti and colleagues. In 2011, 200 patients undertook radical prostatectomy in our institution. Among them 53 patients who fulfilled Briganti criteria and in whom we omitted lymphadenectomy based on current guidelines. Unfavorable clinicopathological features considered were: stage T3, positive surgical margins or biochemical relapse (BCR). We registered biopsy Gleason score 6 in 34 patients, and 19 patients had Gleason score 7. Stage pT2 was seen in 49 patients, and pT3 in 4. Glea-son score after radical prostatectomy was upgraded from GS 6 to GS 7 in 20 patients (37%) and reduced in 1 patient (2%). After a median follow-up of 49 (44-56) months, there were 12 (22.6%) patients with BCR. Patients with biopsy Gleason score 6 (n=34) compared to biopsy Gleason 7 (n=19) patients showed no difference regarding positive margins (p=0.0738) and BCR (p=0,736) at 49 months follow-up. Thus, PLND according to current guidelines can be safely omitted in low-risk patients using Brigantinomogram.

Prostatic Artery Embolization as a New Option in the Treatment of Lower Urinary Tract Symptoms in Benign Prostatic Hyperplasia - Current Evidence.

Prostatic artery embolization is a minimally invasive endovascular treatment that improves lower urinary tract symptoms in men with benign prostatic hyperplasia. Although further randomized studies and long-term evidence is still needed for this method to be fully incorporated into treatment guidelines for benign prostatic hyperplasia, current studies show that this method can be an effective and safe alternative in patients with a significantly enlarged prostate gland who are not good surgical candidates. Therefore, we present the theory, technical details and potential benefits of this method as we review the current evidence on prostatic artery embolization.

Incidental Prostate Cancer in Patients Treated for Benign Prostate Hyperplasia in the Period of 21 Years.

The aim of this study was to determine the incidence of incidental prostate cancer and its clinical significance among patients who underwent transurethral prostate resection or transvesical adenomectomy for benign prostate hyperplasia at the Department of Urology in Sestre milosrdnice University Hospital Center from January 1997 to December 2017. A total of 277/4,372 (6.34%) patients from our cohort were diagnosed with incidental prostate cancer (mean age 74.5 years). Due to incomplete data, 12 patents were excluded from further analysis. 44.91% (119/265 patents) of our cohort were stage T1a and 55.09% (146/265) were stage T1b. Clinically significant prostate cancer was found in 168/265 patients (63.40%). When divided into two groups, Gleason score ≤6 (mean age 73.58 years) and Gleason score ≥7 (mean age 75.77 years), the results showed that Gleason score ≥7 patients were significantly older (p=0.0104) and that the tumor extent among patients in this group (mean = 34.58%) was higher than that in Gleason score ≤6 group (mean = 11.11%) (p=0.0169). More than a half of patients in our cohort had T1b stage prostate cancer. We found that 63.4% of carcinomas were clinically significant, with 52/265 (19,62%) patients affected by ISUP grade 4 and 5 cancers. Based on our research, we cannot give any recommendations regarding incidental prostate cancer treatment due to lacking preoperative (PSA, DRE) and follow-up data.

Transobturator Advance® Sling Suspension for the Treatment of Postprostatectomy Stress Urinary Incontinence.

Stress urinary incontinence (SUI) continues to present a major complication after radical prostatectomy. Suburethral slings represent one of the less invasive options for postprostatectomy SUI, and a more recent addition is a transobturator sling, the AdVance®. We report our results with the AdVance® sling for the management of postoperative SUI. The evaluation was conducted on 47 patients with AdVance® implant for SUI in our institution (November 2010 - June 2017). Measurements included age, etiology of SUI, duration of SUI, follow-up and pad use per day (PPD) pre- and postoperatively. Patients were classified as cured if they used no pads or 1 PPD for security reasons, or as improved if 1-2 PPDs were used and if there was a 50% reduction in pad use per day postoperatively. In our series we observed a reduction of mean PPD of 5.1 (2-8) to 1.7 (0-4) postoperatively. After follow-up and according to our criteria, the cure rate was 51.1% (24/47) and the improvement rate 27.5% (13/47). The overall success rate was 78.6% (37/47). No improvement was observed in 21.4% (10/47) of patients. Failure rates after sling placement for patients with addi-tional treatments following prostatectomy were much higher (60% (3/10) for radiation therapy and 66.7% (4/10) for urethral stricture disease). Our results show favourable cure and improvement rates and are comparable to results from larger series. The most appropriate candidates for the AdVance® sling are patients with mild to moderate postprostatectomy SUI. The results may be even better in patients without additional treatment following prostatectomy, such as radiation therapy or surgery for stricture disease.

Klebsiella Pneumoniaeoxa-48 in a Urology Patient: Case Report

We present an isolate of Klebsiella pneumoniae OXA-48 isolated in a 68-year-old man who underwent radical prostatectomy due to prostate cancer. The antibiotic susceptibility testing to a wide range of antibiotics was performed by disk diffusion method and determination of minimal inhibitory concentrations. The isolate was classified as multidrug-resistant. It showed intermediate susceptibility to imipenem and meropenem, resistance to ertapenem, and sensitivity only to colistin, amikacin, and trimethoprim-sulfamethoxazole. The isolate was positive for ESBLs, negative for AmpC. Polymerase chain reaction and sequencing revealed bla(OXA-48)', bla(CTX-M-15) and bla(SHV-11). The plasmid encoding OXA-48 ß-lactamase did not belong to any known PCR-based replicon typing. According to genotyping, the isolate belonged to ST37.

Impact of Positive Surgical Margins after Radical Prostatectomy on Disease Progression and Adjuvant Treatment in Pathologically Localized Prostate Cancer.

The aim of our study was to evaluate the impact of margin positivity in clinically and pathologically localized prostate cancer (pT2) after radical prostatectomy on biochemical recurrence and time to adjuvant treatment. We analyzed data from 371 patients who underwent radical prostatectomy. At the mean follow up of 36 (25-54) months, impact of margin positivity in pT2 patients on prostate specific antigen (PSA) recurrence and time to introduction of adjuvant treatment was noted. Out of 371 radical prostatectomies there were 277 (74.6%) pT2 and 94 (25.4%) pT3 (locally advanced) prostate cancers. Mean age was 67.6 years, mean Gleason score 6.78, mean preoperative PSA 11.45 ng/mL. Out of 277 pT2 pts., 233 (84%) had negative (SM-) and 44 (16%) positive surgical margins (SM+). Only 3% of SM- pts. had biochemical relapse (BCR). Among pT2 patients with SM+, 18 (41%) had BCR while 26 were free of recurrence at 3 years follow up. Positive surgical margins had an adverse impact on biochemical progression free survival (3% SM- vs. 41% SM+; p<0.001). No difference was found in age, preoperative PSA, Gleason score or follow up between BCR-SM+ and BCR+SM+ patients. Mean time to PSA recurrence in surgical margin positive pT2 patients was 15.7 months. Surgical margin status pT2 disease has an impact on biochemical progression but only 41% of margine positive patients show biochemical recurrence at 3 yr follow up. Not all SM+ patients need to receive treatment after radical prostatectomy. Longer follow up should be awaited to see the impact on overall survival in this group of patients.