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.

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.

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.

Biopsy Quantitative Patohistology and Seral Values of Prostate Specific Antigen-Alpha (1) Antichymotrypsine Complex in Prediction of Adverse Pathology Findings after Radical Prostatectomy.

In this prospective study we examined the utility of parameters obtained on prostate needle biopsy and prostate specific antigen-alpha(1)-antichymotripsine complex (PSA-ACT) to predict adverse pathologic findings after radical prostatectomy. 45 consecutive patients assigned for radical prostatectomy due to clinically localized prostate cancer were included in the study. Prostate biopsy parameters such as number of positive cores, the greatest percentage of tumor in the positive cores, Gleason score, perineural invasion, unilaterality or bilaterality of the tumor were recorded. PSA-ACT was determined using sandwich immunoassay chemiluminiscent method (Bayer, Tarrytown, New York). We analyzed relationship of preoperative PSA, PSA-ACTand quantitative biopsy parameters with final pathology after prostatectomy. Adverse findings were considered when extracapsular extension of cancer (pT3) was noted. Postoperatively, 29 (64.4%) patients were diagnosed with pT2 disease and 16 (35.6%) with pT3 disease. There was a significant difference in localized vs. locally advanced disease in number of positive biopsy cores (p<0.001), greatest percentage of tumor in the core (p=0.008), localization of the tumor (p=0.003) and perineural invasion (p=0.004). Logistic regression was used to develop a model on the multivariate level. It included number of positive cores and PSA-ACT and was significant on our cohort with the reliability of 82.22%. The combination of PSA-ACT and a large scale of biopsy parameters could be used in prediction of adverse pathologic findings after radical prostatectomy. Clinical decisions and patients counselling could be influenced by these predictors but further confirmation on a larger population is necessary.

[Clinical guidelines for diagnosing, treatment and monitoring patients with bladder cancer--Croatian Oncology Society and Croatian Urology Society, Croatian Medical Association]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnika oboljelih od raka mokracnog mjehura Hrvatskoga Onkolokog Drustva i Hrvatskoga Uroloskog Drustva Hrvatskoga Lijecnickog Zbora.

Urothelial cancer is the most common bladder cancer. Hematuria is the most common presenting symptom in patients with bladder cancer. The most common diagnostics of bladder cancer is performed by transurethral resection of bladder after which pathohistological diagnosis is set. It is necessary to determine whether the cancer penetrated in muscle layer (muscle-invasive cancer) or not (muscle-noninvasive cancer). Decision on therapeutic modality depends on the clinical stage of disease and on prognostic and risk factors. For muscle non-invasive bladder cancer transurethral resection is preferred with or without intravesical instillation of Bacillus Calmette-Guérin (BCG). For invasive cancer the method of choice is radical cystectomy. Radiotherapy is used in radical and palliative purposes. Metastatic disease is most frequently treated by chemotherapy metotrexate/vinblastine/doxorubicine/cisplatin (MVAC) or gemcitabine/cisplatin (GC). The purpose of this article is to present clinical recommendations to set standards of procedures and criteria in diagnostics, treatment and follow up of patients with bladder cancer in the Republic of Croatia.

[Clinical guidelines for diagnosing, treatment and monitoring patients with prostate cancer--Croatian Oncology Society and Croatian Urology Society, Croatian Medical Association]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnika oboljelih od raka prostate Hrvatskoga Onkoloskog Drustva i Hrvatskoga Uroloskog Drustva Hrvatskoga Lijecnickog Zbora.

Prostate adenocarcinoma is the second most common solid neoplasm in male population in Croatia. It rarely causes symptoms unless it is advanced. The finding of PSA rise is the most common reason for diagnostic workout. Treatment plan is based on TNM classification, Gleason score and PSA. Clinically localized disease is successfully treated by radical prostatectomy or radiotherapy with or without hormonal therapy. Locally advanced disease is treated with radiotherapy and hormonal therapy. Metastatic disease can be controlled for many years by androgen deprivation. For castration resistant disease appropriate treatment is chemotherapy or secondary hormonal therapy. The following paper presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, management, treatment and monitoring of patients with prostate cancer in the Republic of Croatia.

[Clinical recommendations for treating and monitoring patients with renal cancer]. / Klinicke upute za dijagnozu, lijecenje i pracenje bolesnika oboljelih od raka bubrega.

Clear cell renal carcinoma is the most common kidney cancer. It is generally asymptomatic. A small percentage of patients present with hematuria, flank pain and abdominal mass. It is usually detected accidentally during radiologic examination. The diagnosis of kidney cancer is confirmed by pathohistological findings after completion of the diagnostic process. The decision about treatment is made based on clinical assessment of disease stage and other risk factors. Depending on that, treatment options include surgery, and considering high resistance of kidney cancer on chemotherapy and hormone therapy, use of targeted therapies (immunotherapy, tyrosine kinase inhibitors) and palliative radiotherapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, treatment and monitoring of patients with kidney cancer in the Republic of Croatia.

[Performance Assessment Tool for Quality Improvement in Hospitals (PATH): first experiences in Croatia]. / Alat za ocjenu rada u cilju poboljsanja kvalitete u bolnicama: prva iskustva u provodenju programa PATH u hrvatskim bolnicama.

PATH (Performance Assessment Tool for Quality Improvement in Hospitals), a project of the World Health Organization (WHO) for Europe offers hospitals a comprehensive and standardized tool (a set of indicators) to evaluate their own performance and development of measures for quality improvement. PATH Program was launched in Croatia in 2008, and it was conducted in 2009 in hospitals that have voluntarily decided to be involved. Here we present the results of the first phase of pilot experience of establishing the program, based on data collected in 22 Croatian hospitals. Analysis of the first results indicated the existence of marked differences among the hospitals that have taken the example of the percentage of cesarean sections ranging from 1.1% to 21.4%. The mortality rate of myocardial infarction ranged from 1.9 to 21.4%, while the mortality of stroke ranged from 12.5 to 45.5%. The highest percentage of needle-stick injuries reported for physicians was 16.2% of entire hospital staff in one year, 6.1% for nurses and 4.6% for the supportive staff. The result suggests the existence of many problems and limitations in data collection at hospital level, limitations in their analysis and creates recommendations for quality improvements, which must be taken into account when hospitals are compared on the national or international level.

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.

[Urothelial carcinoma with an inverted growth pattern: a report of 4 cases]. / Urotelni karcinom invertiranog nacina rasta--prikaz 4 bolesnika.

AIM: Urothelial (transitional cell) tumors account for about 90% of all bladder tumors. Their presentation varies from benign lesions that rarely recur to highly malignant tumors. Inverted (endophytic) growth pattern in urothelial carcinoma is particulary hard to distinguish from inverted papilloma. Morphologic criteria alone are not enough and immunohistochemical assesments must also be done, especially in cases of small size biopsy material or transurethral resections. The aim of this study was to accentuate the importance and ways of differentiation of this variable forms as their treatment and prognosis differ. PATIENTS AND METHODS: In the period from 01.01.2008. to 30.06.2009. at Department of Pathology, University Hospital "Sestre milosrdnice" four patients were diagnosed with low-grade urothelial carcinoma with an inverted growth pattern. Routine histology and additional immunohistochemistry to p53, Ki-67 and CK 7 and 20 was performed. RESULTS: There were three male patients aging 37, 61 and 69 years and one female aged 46 (mean 53.3 years). Three patients presented with painless hematuria while the last patient had microhaematuria as an Incidental finding. Histologically, tumors formed nests of atypical urothelial cells. Very few or no mitotic figures were observed. Invasion of lamina propria was present in three specimens. Immunohistochemically, positive staining to p53 and CK 20 was observed in all four cases and staining to CK 7 in two. Staining to CK 20 was positive in 80%-100% of tumor cells while the number of p53 positive cells was between 20% and 40% in all four cases. Proliferative activity was assesed using Ki-67 antibody. The percentage of positively stained tumor cells, assesed in hot spots under high magnification (400x), was 5%, 7%, 8% and 12% (mean 8%). CONCLUSION: Urothelial carcinoma with inverted growth pattern and inverted papilloma have similar morphologic features but their biological behaviour, treatment and prognosis are different. In order to avoid the urothelial carcinoma to be misdiagnosed as a benign papilloma, we find it very important to make additional investigations beside conventional histology. Immunohistochemical staining for CK 20, p53 and Ki-67, which is positive in most carcinomas, can help us make the right diagnosis.

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.

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.

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.

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.

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.