CURRENT ROLE OF MAGNETIC RESONANCE IMAGING IN THE SCREENING, DIAGNOSIS, AND TREATMENT OF PROSTATE CANCER.

Prostate cancer is the most common cancer in men. Diagnosis of prostate cancer poses a significant challenge, due to several different key parameters that need to be evaluated, such as age, history of prostate specific antigen (PSA), clinical examination and more recently magnetic resonance imaging (MRI). The current diagnostic pathway for prostate cancer has resulted in overdiagnosis and overtreatment as well as underdiagnosis and missed diagnoses in many men. Multiparametric MRI (mp-MRI) of the prostate has been identified as a test that could alleviate these diagnostic errors. Before prostate cancer treatment pathological confirmation is mandatory. Prostate biopsy is an invasive procedure with rare but not negligible potential complications. There are several methods of prostate biopsy of which most common are systemic or planar prostate biopsy and cognitive or targeted MRI-guided prostate biopsy. Multiparametric MRI has demonstrated better accuracy and reproducibility in detecting, locating and evaluating prostate cancer and also sparing some men unnecessary biopsies. Recent studies have shown a mpMRI benefit for better procedure planning regarding prostate cancer location, extent of disease and length of the urethra. There are still some challenges ahead, such as ensuring high-quality execution and reporting of mpMRI and ensuring that this diagnostic pathway is cost-effective. According to the latest urological clinical guidelines mpMRI became fundamental tool in management of prostate cancer. The aim of this study is to give a brief insight in use of mpMRI in prostate cancer diagnosis and treatment.

COMPARISON OF GRADING ACCURACY OF PROSTATE CANCER IN SAMPLES ACQUIRED BY A TARGETED AND SYSTEMIC PROSTATE BIOPSY.

Introduction: All malignancies, including prostate cancer, require accurate diagnosing and staging before making a treatment decision. The introduction of targeted biopsies based on prostate MRI findings has raised prostate biopsy accuracy. Guided biopsies target the tumor itself during the biopsy instead of the most common tumor sites as is the case with a systemic biopsy. Some studies report that targeted biopsies should lower prostate cancer biopsy undergrading and overgrading. Goals: To determine the incidence of prostate cancer biopsy undergrading in patients who underwent a classic systemic biopsy compared to patients who underwent a mpMRI cognitive targeted biopsy. Materials and methods: We identified the patients from our database who underwent a radical prostatectomy at our institution from January 1st, 2021, to June 30th, 2021.There were 112 patients identified. Patients were stratified into two groups based on the type of biopsy that confirmed prostate cancer. The mpMRI (N=50) group had a mpMRI cognitive guided transrectal ultrasound (TRUS) prostate biopsy performed, and the non-mpMRI group (N=62) received a classic, systemic TRUS biopsy. We compared the biopsy results with the final pathological results, and searched for undergrading or overgrading in the biopsies compared to the final histological report. Results: The undergrading was found in 17,7% (N=11) cases in the non-mpMRI group and in 12,0% (N=6) of cases in the mpMRI group (p=0,02, Mann-Whitney U test). No overgrading was found in our cohort. All cases of undergrading had Grade Group 1 in the biopsy report and Grade Group 2 in the final specimen report. The charasteristics of patients are listed in Table 1. Discussion and conclusion: In our cohort, the patients who underwent a mpMRI targeted biopsy had a lower undergrading incidence. During a systemic TRUS biopsy, the urologist targets the areas of the prostate where cancer is most commonly located, which is usually the peripheral zone of the prostate. Since different areas of the tumor have different areas of differentiation, only a low-grade part of the tumor is sometimes biopsied, which results in a sampling error. Once the prostate is removed, the whole tumor is analyzed, so the obtained pathological results related to the removed prostate are far more accurate than the analysis of prostate cores obtained by biopsy.

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.

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.

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.

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.

A RARE CASE OF SQUAMOUS CELL CARCINOMA IN URINARY BLADDER DIVERTICULUM SUCCESSFULLY TREATED BY BLADDER-SPARING SURGERY.

The aim is to report a rare case of squamous cell carcinoma arising in a urinary bladder diverticulum and present recent literature overview of treatment options. A 56-year-old man presented with intermittent hematuria. Ultrasound examination indicated primary carcinoma in the urinary bladder diverticulum. Diagnosis was confirmed with cystoscopy and computed tomography. Transvesical diverticulectomy with regional lymphadenectomy was undertaken. Two years after initial treatment, the patient was well without evidence of tumor relapse. This report implicates that although aggressive surgical approach is recommended in the majority of bladder diverticulum tumors, simple diverticulectomy may be indicated in selected, confined cases.

Endemic (Balkan) nephropathy is aristolochic acid nephropathy.

Endemic nephropathy is a syndrome that comprises two entities: chronic interstitial nephropathy and urothelial cell cancers predominantly of the upper urinary tract. The etiological agent for the disease is aristolochic acid, a compound found in the plants of Aristolochia spp. The development of urothelial cancers is characterized by the formation of aristolactam DNA adducts leading to mutations, predominantly A: T->T: A transversions. In order to comprehensively understand the gene regulation programs in upper urothelial cancers we performed integrated miRNA and mRNA expression profiling of paired tumours and unaffected urothelium samples. The obtained data will help us to understand the carcinogenesis caused by aristolochic acid and might be the source for the design of a diagnostic biomarker.

Variation in presentation and presence of DNA adducts and p53 mutations in patients with endemic nephropathy--an environmental form of the aristolochic acid nephropathy.

BACKGROUND: Endemic nephropathy (EN) and associated urothelial cell cancers (UUC) are an environmental form of aristolochic acid nephropathy where the most probable rout of ingestion of aristolochic acid (AA) was made by bread contaminated with AA, leading to chronic dietary intoxication. Clinical courses of three members of the same family, similarly exposed to toxin, who exhibited different clinical courses of the disease are presented. METHODS: Questionnaires on AA exposure were taken. Tissue samples were obtained during therapeutic nephrouretectomies. Histopathology, immunohistochemical detection of p53, p53 mutation screening in tumor DNA and analysis on the presence of aristolactam (AL)-DNA adducts were performed. RESULTS: Case 1 had UUC with typical EN histopathological signs, whereas Case 2 had bilateral UUCs with typical EN histopathological signs. In contrast, the patient in Case 3 initially showed renal insufficiency, complicated afterwards by right UUC, and later on by left UUC with histopathological end-stage chronic changes but without typical EN changes. AA-DNA adducts and specific p53 mutational spectra (A:T→ T:A transversion) were found in tissues of cases 1 and 2. CONCLUSION: Diverse clinical courses seem to be related not to differences in exposure but to differences in metabolic activation or detoxification of AA and/or DNA repair resulting from different genetic polymorphisms.